Ctnnb1

UniProt ID: Q02248
Organism: Mus musculus
Review Status: COMPLETE
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Gene Description

Beta-catenin is a multifunctional Armadillo-repeat protein with two conserved core roles: at adherens junctions it binds classical cadherins and alpha-catenin to support cadherin-mediated cell-cell adhesion, and in canonical Wnt signaling it accumulates in the nucleus and acts as a transcriptional coactivator with TCF/LEF-family DNA-binding transcription factors. These molecular roles explain the many developmental, proliferative, differentiation, and tissue-patterning phenotypes in mouse; those organismal processes are generally downstream context-specific consequences rather than separate core molecular functions.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0001525 angiogenesis
IMP
PMID:28463231
Disruption of lineage specification in adult pulmonary mesen... 		KEEP AS NON CORE
Summary: Beta-catenin promotes angiogenesis via endothelial Wnt/TCF transcription and adherens-junction integrity; a vascular developmental consequence, not a core function.
Reason: downstream vascular outcome of Wnt and junction roles
Supporting Evidence:
PMID:28463231
Disruption of lineage specification in adult pulmonary mesenchymal progenitor cells promotes microvascular dysfunction.
GO:0001708 cell fate specification
IMP
PMID:28463231
Disruption of lineage specification in adult pulmonary mesen... 		KEEP AS NON CORE
Summary: Beta-catenin specifies cell fates via context-dependent Wnt target activation; a developmental specification outcome, not a proximal molecular mechanism.
Reason: downstream Wnt-driven fate specification
Supporting Evidence:
PMID:28463231
Disruption of lineage specification in adult pulmonary mesenchymal progenitor cells promotes microvascular dysfunction.
GO:0019221 cytokine-mediated signaling pathway
IMP
PMID:19619491
Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-... 		KEEP AS NON CORE
Summary: Beta-catenin intersects cytokine-responsive transcription via Wnt crosstalk in development/immunity; an indirect signaling outcome rather than a direct cytokine-pathway role.
Reason: indirect crosstalk; downgrade from UNDECIDED to non-core
Supporting Evidence:
PMID:19619491
Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
GO:0002064 epithelial cell development
IMP
PMID:16102745
The duality of beta-catenin function: a requirement in lens ... 		KEEP AS NON CORE
Summary: Beta-catenin supports epithelial cell development via junction-mediated polarity and Wnt transcription; an epithelial differentiation outcome downstream of its dual role.
Reason: downstream of junction/Wnt epithelial roles
Supporting Evidence:
PMID:16102745
The duality of beta-catenin function: a requirement in lens morphogenesis and signaling suppression of lens fate in periocular ectoderm.
GO:0001944 vasculature development
IMP
PMID:25083995
Canonical WNT signaling components in vascular development a... 		KEEP AS NON CORE
Summary: Whole-vasculature development depends on beta-catenin Wnt signaling in endothelium; a broad downstream organ-system phenotype.
Reason: System-level vascular development downstream of Wnt/beta-catenin output.
Supporting Evidence:
PMID:25083995
Canonical WNT signaling components in vascular development and barrier formation.
GO:0010467 gene expression
IMP
PMID:25083995
Canonical WNT signaling components in vascular development a... 		MARK AS OVER ANNOTATED
Summary: The broad 'gene expression' parent is uninformative; beta-catenin's specific role is coactivation of TCF/LEF target gene transcription by Pol II.
Reason: Overly broad parent superseded by specific Pol II transcription terms.
Supporting Evidence:
PMID:25083995
Canonical WNT signaling components in vascular development and barrier formation.
GO:0000122 negative regulation of transcription by RNA polymerase II
IDA
PMID:16040629
Beta-catenin regulates differentiation of respiratory epithe... 		KEEP AS NON CORE
Summary: An IDA call; beta-catenin represses certain Pol II targets in specific contexts, but this should be downgraded relative to its core activating coactivator role, not removed.
Reason: Experimental (IDA); downgrade context-specific repression, do not REMOVE.
Supporting Evidence:
PMID:16040629
Beta-catenin regulates differentiation of respiratory epithelial cells in vivo.
GO:0000165 MAPK cascade
IGI
PMID:16478791
APC inhibits ERK pathway activation and cellular proliferati... 		KEEP AS NON CORE
Summary: IGI evidence links beta-catenin to MAPK signaling, but this is signaling crosstalk and not a core function of the Wnt effector.
Reason: Crosstalk pathway, not the gene's central Wnt/transcription function.
Supporting Evidence:
PMID:16478791
APC inhibits ERK pathway activation and cellular proliferation induced by RAS.
GO:0000578 embryonic axis specification
IDA
PMID:9230313
The mouse Fused locus encodes Axin, an inhibitor of the Wnt ... 		KEEP AS NON CORE
Summary: Beta-catenin establishes the primary embryonic axis (organizer formation) via nuclear Wnt/TCF activation (IDA); a hallmark downstream developmental outcome of its signaling role.
Reason: downstream Wnt-driven embryonic axis formation
Supporting Evidence:
PMID:9230313
The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.
GO:0000902 cell morphogenesis
IMP
PMID:16102745
The duality of beta-catenin function: a requirement in lens ... 		KEEP AS NON CORE
Summary: Beta-catenin shapes cell morphology via adherens-junction cytoskeletal linkage and Wnt transcription; a morphogenetic outcome of its dual structural/signaling roles.
Reason: downstream of junction and Wnt roles
Supporting Evidence:
PMID:16102745
The duality of beta-catenin function: a requirement in lens morphogenesis and signaling suppression of lens fate in periocular ectoderm.
GO:0001501 skeletal system development
IMP
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts fr... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling shapes skeletal patterning and ossification broadly; a high-level downstream organ-system phenotype.
Reason: System-level skeletal development downstream of Wnt transcription.
Supporting Evidence:
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
GO:0001569 branching involved in blood vessel morphogenesis
IMP
PMID:12975353
The conditional inactivation of the beta-catenin gene in end... 		KEEP AS NON CORE
Summary: Endothelial beta-catenin drives vessel branching through Wnt/TCF transcription and junction remodeling; a vascular morphogenetic outcome downstream of its dual role.
Reason: downstream vascular branching from Wnt/junction roles
Supporting Evidence:
PMID:12975353
The conditional inactivation of the beta-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility.
GO:0001569 branching involved in blood vessel morphogenesis
IMP
PMID:19154719
Nrarp coordinates endothelial Notch and Wnt signaling to con... 		KEEP AS NON CORE
Summary: Endothelial beta-catenin drives vessel branching through Wnt/TCF transcription and junction remodeling; a vascular morphogenetic outcome downstream of its dual role.
Reason: downstream vascular branching from Wnt/junction roles
Supporting Evidence:
PMID:19154719
Nrarp coordinates endothelial Notch and Wnt signaling to control vessel density in angiogenesis.
GO:0001570 vasculogenesis
IMP
PMID:18231602
Formation and differentiation of multiple mesenchymal lineag... 		KEEP AS NON CORE
Summary: De novo vessel formation requires Wnt/beta-catenin transcriptional control of endothelial precursors; a downstream developmental process.
Reason: Vasculogenesis downstream of Wnt-driven endothelial transcription.
Supporting Evidence:
PMID:18231602
Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
GO:0001649 osteoblast differentiation
IMP
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts fr... 		KEEP AS NON CORE
Summary: Wnt/beta-catenin is a master driver of osteoblast fate via Runx2/Osterix-linked targets; the differentiation outcome is downstream of that transcription.
Reason: Osteoblastogenesis downstream of Wnt/beta-catenin transcriptional program.
Supporting Evidence:
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
GO:0001658 branching involved in ureteric bud morphogenesis
IMP
PMID:17537789
Wnt/beta-catenin signaling regulates nephron induction durin... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling drives ureteric bud branching in kidney development; a renal morphogenetic outcome downstream of TCF target activation.
Reason: downstream Wnt-driven renal branching morphogenesis
Supporting Evidence:
PMID:17537789
Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development.
GO:0001701 in utero embryonic development
IMP
PMID:18231602
Formation and differentiation of multiple mesenchymal lineag... 		KEEP AS NON CORE
Summary: Beta-catenin is essential for embryonic viability/development in utero via Wnt signaling and adhesion (IGI/IMP); a broad developmental outcome of its dual role, not core function.
Reason: downstream of Wnt/junction roles in embryogenesis
Supporting Evidence:
PMID:18231602
Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
GO:0001701 in utero embryonic development
IGI
PMID:19204372
Both the RGS domain and the six C-terminal amino acids of mo... 		KEEP AS NON CORE
Summary: Beta-catenin is essential for embryonic viability/development in utero via Wnt signaling and adhesion (IGI/IMP); a broad developmental outcome of its dual role, not core function.
Reason: downstream of Wnt/junction roles in embryogenesis
Supporting Evidence:
PMID:19204372
Both the RGS domain and the six C-terminal amino acids of mouse Axin are required for normal embryogenesis.
GO:0001702 gastrulation with mouth forming second
IMP
PMID:8582267
Lack of beta-catenin affects mouse development at gastrulati... 		KEEP AS NON CORE
Summary: Beta-catenin drives deuterostome gastrulation/germ-layer movements via Wnt-driven organizer transcription; an early morphogenetic outcome downstream of signaling.
Reason: downstream Wnt-driven gastrulation
Supporting Evidence:
PMID:8582267
Lack of beta-catenin affects mouse development at gastrulation.
GO:0001706 endoderm formation
IMP
PMID:12194849
Formation of multiple hearts in mice following deletion of b... 		KEEP AS NON CORE
Summary: Beta-catenin promotes definitive endoderm formation through nuclear Wnt/TCF activation; a germ-layer developmental outcome downstream of signaling.
Reason: downstream Wnt-driven endoderm formation
Supporting Evidence:
PMID:12194849
Formation of multiple hearts in mice following deletion of beta-catenin in the embryonic endoderm.
GO:0001706 endoderm formation
IMP
PMID:23824574
Wnt/Ξ²-catenin signalling regulates Sox17 expression and is e... 		KEEP AS NON CORE
Summary: Beta-catenin promotes definitive endoderm formation through nuclear Wnt/TCF activation; a germ-layer developmental outcome downstream of signaling.
Reason: downstream Wnt-driven endoderm formation
Supporting Evidence:
PMID:23824574
Wnt/Ξ²-catenin signalling regulates Sox17 expression and is essential for organizer and endoderm formation in the mouse.
GO:0001708 cell fate specification
IMP
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts fr... 		KEEP AS NON CORE
Summary: Beta-catenin specifies cell fates via context-dependent Wnt target activation; a developmental specification outcome, not a proximal molecular mechanism.
Reason: downstream Wnt-driven fate specification
Supporting Evidence:
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
GO:0001711 endodermal cell fate commitment
IMP
PMID:12194849
Formation of multiple hearts in mice following deletion of b... 		KEEP AS NON CORE
Summary: Beta-catenin commits cells to endodermal fate via Wnt target-gene activation; a cell-fate outcome downstream of its transcriptional effector role.
Reason: downstream Wnt-driven endoderm commitment
Supporting Evidence:
PMID:12194849
Formation of multiple hearts in mice following deletion of beta-catenin in the embryonic endoderm.
GO:0001764 neuron migration
IGI
PMID:21937711
ASPM regulates Wnt signaling pathway activity in the develop... 		KEEP AS NON CORE
Summary: Beta-catenin affects neuronal migration through combined cadherin-adhesion and Wnt-transcriptional roles; a downstream CNS phenotype (genetic interaction).
Reason: Neuron migration downstream of adhesion plus Wnt transcription.
Supporting Evidence:
PMID:21937711
ASPM regulates Wnt signaling pathway activity in the developing brain.
GO:0001822 kidney development
IMP
PMID:17537789
Wnt/beta-catenin signaling regulates nephron induction durin... 		KEEP AS NON CORE
Summary: Beta-catenin drives nephrogenesis and tubule patterning via Wnt/TCF transcription; a renal organ-development outcome downstream of signaling.
Reason: downstream Wnt-driven kidney development
Supporting Evidence:
PMID:17537789
Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development.
GO:0001840 neural plate development
IDA
PMID:22102609
Increased Ξ²-catenin activity in the anterior neural plate in... 		KEEP AS NON CORE
Summary: Beta-catenin patterns the early neural plate through Wnt-dependent anteroposterior transcriptional control; an IDA developmental phenotype downstream of signaling.
Reason: Neural plate patterning downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:22102609
Increased Ξ²-catenin activity in the anterior neural plate induces ectopic mid-hindbrain characteristics.
GO:0001894 tissue homeostasis
IMP
PMID:18635608
Tissue-specific requirements of beta-catenin in external gen... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling maintains adult tissue homeostasis (e.g. gut crypt renewal); a broad downstream organismal phenotype.
Reason: Tissue homeostasis downstream of Wnt/beta-catenin self-renewal transcription.
Supporting Evidence:
PMID:18635608
Tissue-specific requirements of beta-catenin in external genitalia development.
GO:0001944 vasculature development
IMP
PMID:19129494
Wnt/beta-catenin signaling is required for CNS, but not non-... 		KEEP AS NON CORE
Summary: Whole-vasculature development depends on beta-catenin Wnt signaling in endothelium; a broad downstream organ-system phenotype.
Reason: System-level vascular development downstream of Wnt/beta-catenin output.
Supporting Evidence:
PMID:19129494
Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis.
GO:0002052 positive regulation of neuroblast proliferation
IGI
PMID:21937711
ASPM regulates Wnt signaling pathway activity in the develop... 		KEEP AS NON CORE
Summary: Beta-catenin positively drives neuroblast expansion through Wnt cell-cycle targets; a downstream neurodevelopmental proliferative role.
Reason: Pro-neuroblast proliferation downstream of Wnt transcription.
Supporting Evidence:
PMID:21937711
ASPM regulates Wnt signaling pathway activity in the developing brain.
GO:0002053 positive regulation of mesenchymal cell proliferation
IMP
PMID:18231602
Formation and differentiation of multiple mesenchymal lineag... 		KEEP AS NON CORE
Summary: Beta-catenin expands mesenchymal cells via Wnt mitogenic targets during organogenesis; a downstream proliferative phenotype.
Reason: Mesenchymal proliferation downstream of Wnt mitogenic transcription.
Supporting Evidence:
PMID:18231602
Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
GO:0002053 positive regulation of mesenchymal cell proliferation
IMP
PMID:18533146
An FGF-WNT gene regulatory network controls lung mesenchyme ... 		KEEP AS NON CORE
Summary: Beta-catenin expands mesenchymal cells via Wnt mitogenic targets during organogenesis; a downstream proliferative phenotype.
Reason: Mesenchymal proliferation downstream of Wnt mitogenic transcription.
Supporting Evidence:
PMID:18533146
An FGF-WNT gene regulatory network controls lung mesenchyme development.
GO:0002062 chondrocyte differentiation
IMP
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts fr... 		KEEP AS NON CORE
Summary: Beta-catenin gates chondrocyte vs osteoblast fate via Wnt/TCF transcription; a skeletal cell-fate outcome downstream of its signaling effector role.
Reason: downstream Wnt-driven chondrocyte fate
Supporting Evidence:
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
GO:0002062 chondrocyte differentiation
IGI
PMID:16818445
Wnt9a signaling is required for joint integrity and regulati... 		KEEP AS NON CORE
Summary: Beta-catenin gates chondrocyte vs osteoblast fate via Wnt/TCF transcription; a skeletal cell-fate outcome downstream of its signaling effector role.
Reason: downstream Wnt-driven chondrocyte fate
Supporting Evidence:
PMID:16818445
Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis.
GO:0002089 lens morphogenesis in camera-type eye
IMP
PMID:16102745
The duality of beta-catenin function: a requirement in lens ... 		KEEP AS NON CORE
Summary: Beta-catenin (tightly regulated) shapes lens morphogenesis via Wnt transcription and epithelial junctions; an ocular morphogenetic outcome of its dual role.
Reason: downstream of Wnt/junction roles in lens
Supporting Evidence:
PMID:16102745
The duality of beta-catenin function: a requirement in lens morphogenesis and signaling suppression of lens fate in periocular ectoderm.
GO:0003266 regulation of secondary heart field cardioblast proliferation
IDA
PMID:19620969
A regulatory pathway involving Notch1/beta-catenin/Isl1 dete... 		KEEP AS NON CORE
Summary: Beta-catenin controls cardioblast proliferation in the second heart field via Wnt mitogenic targets; an IDA downstream cardiac phenotype.
Reason: SHF cardioblast proliferation downstream of Wnt transcription.
Supporting Evidence:
PMID:19620969
A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate.
GO:0003338 metanephros morphogenesis
IMP
PMID:19060336
A Wnt7b-dependent pathway regulates the orientation of epith... 		KEEP AS NON CORE
Summary: Beta-catenin shapes metanephric kidney morphogenesis via Wnt/TCF transcription; a renal morphogenetic outcome downstream of signaling.
Reason: downstream Wnt-driven metanephros morphogenesis
Supporting Evidence:
PMID:19060336
A Wnt7b-dependent pathway regulates the orientation of epithelial cell division and establishes the cortico-medullary axis of the mammalian kidney.
GO:0003340 negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis
IDA
PMID:17537789
Wnt/beta-catenin signaling regulates nephron induction durin... 		KEEP AS NON CORE
Summary: In kidney development beta-catenin tunes MET during nephrogenesis via Wnt-target transcription; the IDA is a specific developmental phenotype, not the proximal activity.
Reason: Specific kidney MET-regulation phenotype downstream of beta-catenin Wnt transcriptional control of nephron epithelialization.
Supporting Evidence:
PMID:17537789
Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development.
GO:0006351 DNA-templated transcription
IMP
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts fr... 		MARK AS OVER ANNOTATED
Summary: beta-catenin is not part of the basal transcription machinery; it is a TCF/LEF coactivator. The bare 'DNA-templated transcription' parent is uninformative relative to its specific Pol II coactivator role.
Reason: Generic transcription parent; its real role is captured by transcription coactivator / positive regulation of Pol II transcription.
Supporting Evidence:
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
GO:0006357 regulation of transcription by RNA polymerase II
IDA
PMID:12235125
Beta-catenin-induced melanoma growth requires the downstream... 		MODIFY
Summary: Essence correct but the directionless parent under-specifies beta-catenin's role; it functions specifically as a POSITIVE regulator/coactivator of Pol II transcription.
Reason: Generic regulation parent; specialize to positive regulation of Pol II transcription.
Supporting Evidence:
PMID:12235125
Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor.
GO:0006357 regulation of transcription by RNA polymerase II
IDA
PMID:12464179
Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway m... 		MODIFY
Summary: Essence correct but the directionless parent under-specifies beta-catenin's role; it functions specifically as a POSITIVE regulator/coactivator of Pol II transcription.
Reason: Generic regulation parent; specialize to positive regulation of Pol II transcription.
Supporting Evidence:
PMID:12464179
Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.
GO:0006357 regulation of transcription by RNA polymerase II
IMP
PMID:20043884
Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling wit... 		MODIFY
Summary: Essence correct but the directionless parent under-specifies beta-catenin's role; it functions specifically as a POSITIVE regulator/coactivator of Pol II transcription.
Reason: Generic regulation parent; specialize to positive regulation of Pol II transcription.
Supporting Evidence:
PMID:20043884
Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling within the Apical Ectodermal Ridge (AER) regulates interdigit formation.
GO:0006366 transcription by RNA polymerase II
IDA
PMID:15907834
Wnt/beta-catenin signaling acts upstream of N-myc, BMP4, and... 		MARK AS OVER ANNOTATED
Summary: beta-catenin is not a component of the Pol II transcription apparatus; this bare process term over-annotates its specific coactivator function.
Reason: Uninformative process term; coactivator/positive-regulation terms preferred.
Supporting Evidence:
PMID:15907834
Wnt/beta-catenin signaling acts upstream of N-myc, BMP4, and FGF signaling to regulate proximal-distal patterning in the lung.
GO:0007160 cell-matrix adhesion
IMP
PMID:15131783
Inducible Cre-mediated control of gene expression in the mur... 		UNDECIDED
Summary: Cell-matrix adhesion is not a recognized beta-catenin function (it acts at cell-cell, not cell-ECM, junctions); the IMP basis cannot be verified here.
Reason: Likely indirect/mislabeled, but IMP experimental annotation β€” do not REMOVE; flag for review.
Supporting Evidence:
PMID:15131783
Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin.
GO:0007249 canonical NF-kappaB signal transduction
IMP
PMID:19619491
Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-... 		KEEP AS NON CORE
Summary: An IMP annotation; beta-catenin has documented crosstalk with NF-kappaB, but this is not its core function and the experimental call should be downgraded, not removed.
Reason: Experimental (IMP) crosstalk annotation; downgrade rather than REMOVE.
Supporting Evidence:
PMID:19619491
Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
GO:0007268 chemical synaptic transmission
IMP
PMID:14622577
Role of beta-catenin in synaptic vesicle localization and pr... 		KEEP AS NON CORE
Summary: Beta-catenin contributes to synaptic structure/vesicle organization at junctions affecting transmission; a neuronal outcome downstream of its adhesion role.
Reason: downstream of synaptic adhesion organization
Supporting Evidence:
PMID:14622577
Role of beta-catenin in synaptic vesicle localization and presynaptic assembly.
GO:0007398 ectoderm development
IMP
PMID:8582267
Lack of beta-catenin affects mouse development at gastrulati... 		KEEP AS NON CORE
Summary: Beta-catenin guides ectodermal development through Wnt-driven fate and morphogenesis; a germ-layer developmental outcome downstream of its transcriptional role.
Reason: downstream Wnt-driven ectoderm development
Supporting Evidence:
PMID:8582267
Lack of beta-catenin affects mouse development at gastrulation.
GO:0007403 glial cell fate determination
IDA
PMID:17706960
Persistent expression of stabilized beta-catenin delays matu... 		KEEP AS NON CORE
Summary: Beta-catenin biases neural progenitors toward glial fate via Wnt/TCF transcription (IDA); a CNS cell-fate outcome downstream of signaling.
Reason: downstream Wnt-driven glial fate determination
Supporting Evidence:
PMID:17706960
Persistent expression of stabilized beta-catenin delays maturation of radial glial cells into intermediate progenitors.
GO:0007405 neuroblast proliferation
IGI
PMID:21937711
ASPM regulates Wnt signaling pathway activity in the develop... 		KEEP AS NON CORE
Summary: Beta-catenin expands neuroblasts via Wnt mitogenic targets in genetic-interaction assays; a downstream CNS proliferative phenotype.
Reason: Neuroblast proliferation downstream of Wnt mitogenic transcription.
Supporting Evidence:
PMID:21937711
ASPM regulates Wnt signaling pathway activity in the developing brain.
GO:0007507 heart development
IMP
PMID:12464179
Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway m... 		KEEP AS NON CORE
Summary: Beta-catenin contributes broadly to cardiac development through Wnt-driven progenitor programs and junctions; an organ-development outcome of its dual role, not core function.
Reason: downstream Wnt/junction-driven heart development
Supporting Evidence:
PMID:12464179
Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.
GO:0008104 intracellular protein localization
IMP
PMID:16621792
Membrane localization of adenomatous polyposis coli protein ... 		KEEP AS NON CORE
Summary: Beta-catenin contributes to localizing partner proteins (e.g. junctional/synaptic cargo), a secondary process distinct from its own core roles.
Reason: Peripheral process; IMP.
Supporting Evidence:
PMID:16621792
Membrane localization of adenomatous polyposis coli protein at cellular protrusions: targeting sequences and regulation by beta-catenin.
GO:0008283 cell population proliferation
IMP
PMID:19690384
Wnt signaling regulates smooth muscle precursor development ... 		MARK AS OVER ANNOTATED
Summary: Generic proliferation umbrella conveying nothing beta-catenin-specific; specific tissue-proliferation terms already capture Wnt-driven growth roles.
Reason: vague proliferation umbrella adds no specificity
Supporting Evidence:
PMID:19690384
Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.
GO:0008283 cell population proliferation
IMP
PMID:15131783
Inducible Cre-mediated control of gene expression in the mur... 		MARK AS OVER ANNOTATED
Summary: Generic proliferation umbrella conveying nothing beta-catenin-specific; specific tissue-proliferation terms already capture Wnt-driven growth roles.
Reason: vague proliferation umbrella adds no specificity
Supporting Evidence:
PMID:15131783
Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin.
GO:0008284 positive regulation of cell population proliferation
IMP
PMID:19690384
Wnt signaling regulates smooth muscle precursor development ... 		KEEP AS NON CORE
Summary: Beta-catenin drives proliferation via Wnt mitogenic targets (Myc, cyclin D1); a key but downstream consequence of its transcriptional coactivation.
Reason: Proliferation downstream of Wnt target genes Myc/CcnD1; non-core.
Supporting Evidence:
PMID:19690384
Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.
GO:0008543 fibroblast growth factor receptor signaling pathway
IMP
PMID:18533146
An FGF-WNT gene regulatory network controls lung mesenchyme ... 		KEEP AS NON CORE
Summary: Beta-catenin intersects FGFR signaling indirectly through Wnt/FGF developmental crosstalk; an experimental (IMP) phenotype downstream of signaling integration, not a core FGFR-pathway role.
Reason: experimental; indirect FGF/Wnt crosstalk, downgrade not remove
Supporting Evidence:
PMID:18533146
An FGF-WNT gene regulatory network controls lung mesenchyme development.
GO:0009948 anterior/posterior axis specification
IMP
PMID:10662781
Requirement for beta-catenin in anterior-posterior axis form... 		KEEP AS NON CORE
Summary: Beta-catenin patterns the A/P axis through nuclear Wnt/TCF target activation in early embryo; an axial patterning outcome downstream of its transcriptional effector role.
Reason: downstream Wnt-driven axial patterning
Supporting Evidence:
PMID:10662781
Requirement for beta-catenin in anterior-posterior axis formation in mice.
GO:0009950 dorsal/ventral axis specification
IMP
PMID:12923052
Genetic interaction between Wnt/beta-catenin and BMP recepto... 		KEEP AS NON CORE
Summary: Beta-catenin contributes to D/V axial specification through nuclear Wnt target activation; an axial patterning outcome downstream of its effector role.
Reason: downstream Wnt-driven D/V axis specification
Supporting Evidence:
PMID:12923052
Genetic interaction between Wnt/beta-catenin and BMP receptor signaling during formation of the AER and the dorsal-ventral axis in the limb.
GO:0009953 dorsal/ventral pattern formation
IMP
PMID:15708565
Effects of canonical Wnt signaling on dorso-ventral specific... 		KEEP AS NON CORE
Summary: Beta-catenin participates in D/V pattern formation via Wnt/TCF transcriptional readout; a tissue-patterning outcome, not a proximal mechanism.
Reason: downstream Wnt-driven D/V patterning
Supporting Evidence:
PMID:15708565
Effects of canonical Wnt signaling on dorso-ventral specification of the mouse telencephalon.
GO:0009954 proximal/distal pattern formation
IMP
PMID:12885771
beta-Catenin is required for specification of proximal/dista... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling contributes to proximodistal patterning (e.g. limb/organ axes) via target-gene gradients; a downstream patterning phenotype.
Reason: P/D patterning downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:12885771
beta-Catenin is required for specification of proximal/distal cell fate during lung morphogenesis.
GO:0010463 mesenchymal cell proliferation
IMP
PMID:18231602
Formation and differentiation of multiple mesenchymal lineag... 		KEEP AS NON CORE
Summary: Beta-catenin promotes mesenchymal proliferation via Wnt target-gene activation; a connective-tissue growth outcome downstream of its transcriptional role.
Reason: downstream Wnt-driven mesenchymal proliferation
Supporting Evidence:
PMID:18231602
Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
GO:0010463 mesenchymal cell proliferation
IMP
PMID:18533146
An FGF-WNT gene regulatory network controls lung mesenchyme ... 		KEEP AS NON CORE
Summary: Beta-catenin promotes mesenchymal proliferation via Wnt target-gene activation; a connective-tissue growth outcome downstream of its transcriptional role.
Reason: downstream Wnt-driven mesenchymal proliferation
Supporting Evidence:
PMID:18533146
An FGF-WNT gene regulatory network controls lung mesenchyme development.
GO:0010468 regulation of gene expression
IMP
PMID:22102609
Increased Ξ²-catenin activity in the anterior neural plate in... 		MARK AS OVER ANNOTATED
Summary: Very broad regulatory parent; beta-catenin's specific role is TCF/LEF coactivation regulating Pol II transcription of Wnt targets.
Reason: Top-level generic parent; specific Pol II coactivation terms preferred.
Supporting Evidence:
PMID:22102609
Increased Ξ²-catenin activity in the anterior neural plate induces ectopic mid-hindbrain characteristics.
GO:0010628 positive regulation of gene expression
IMP
PMID:18231602
Formation and differentiation of multiple mesenchymal lineag... 		MARK AS OVER ANNOTATED
Summary: Broad parent; beta-catenin's specific activating role is coactivation of TCF/LEF target gene transcription by Pol II, captured by more precise terms.
Reason: Uninformative broad parent superseded by Pol II coactivation terms.
Supporting Evidence:
PMID:18231602
Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
GO:0010628 positive regulation of gene expression
IMP
PMID:19690384
Wnt signaling regulates smooth muscle precursor development ... 		MARK AS OVER ANNOTATED
Summary: Broad parent; beta-catenin's specific activating role is coactivation of TCF/LEF target gene transcription by Pol II, captured by more precise terms.
Reason: Uninformative broad parent superseded by Pol II coactivation terms.
Supporting Evidence:
PMID:19690384
Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.
GO:0010718 positive regulation of epithelial to mesenchymal transition
ISO
GO_REF:0000008 		KEEP AS NON CORE
Summary: Nuclear beta-catenin drives EMT transcriptional programs (Snail/Twist targets) while loss of its junctional pool also promotes EMT; the process is downstream of both core roles.
Reason: EMT is a transcriptional/adhesion downstream output, not beta-catenin's direct molecular function.
GO:0016331 morphogenesis of embryonic epithelium
IMP
PMID:16102745
The duality of beta-catenin function: a requirement in lens ... 		KEEP AS NON CORE
Summary: Embryonic epithelial shaping requires Wnt/beta-catenin transcriptional output plus cadherin-junction adhesion, but the morphogenetic outcome is downstream of those proximal roles.
Reason: Downstream tissue morphogenesis driven by beta-catenin's Wnt-transcription and adhesion roles, not a molecular function.
Supporting Evidence:
PMID:16102745
The duality of beta-catenin function: a requirement in lens morphogenesis and signaling suppression of lens fate in periocular ectoderm.
GO:0021819 layer formation in cerebral cortex
IMP
PMID:20503375
Expression analysis of an evolutionarily conserved metalloph... 		KEEP AS NON CORE
Summary: Beta-catenin influences cortical layering through Wnt/adhesion-dependent neural development, a tissue-specific developmental output.
Reason: Developmental neuronal role; IMP, non-core.
Supporting Evidence:
PMID:20503375
Expression analysis of an evolutionarily conserved metallophosphodiesterase gene, Mpped1, in the normal and beta-catenin-deficient malformed dorsal telencephalon.
GO:0022009 central nervous system vasculogenesis
IMP
PMID:19023080
Canonical Wnt signaling regulates organ-specific assembly an... 		KEEP AS NON CORE
Summary: Beta-catenin drives CNS vessel formation through endothelial Wnt/TCF transcription; a neurovascular developmental outcome, not core function.
Reason: downstream Wnt-driven CNS vasculogenesis
Supporting Evidence:
PMID:19023080
Canonical Wnt signaling regulates organ-specific assembly and differentiation of CNS vasculature.
GO:0022405 hair cycle process
IMP
PMID:11371349
beta-Catenin controls hair follicle morphogenesis and stem c... 		KEEP AS NON CORE
Summary: Beta-catenin drives hair-follicle cycling (anagen entry) via Wnt/TCF transcription in follicle stem cells; a skin-appendage outcome downstream of signaling.
Reason: downstream Wnt-driven hair cycling
Supporting Evidence:
PMID:11371349
beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin.
GO:0030097 hemopoiesis
IDA
PMID:12717450
A role for Wnt signalling in self-renewal of haematopoietic ... 		KEEP AS NON CORE
Summary: Beta-catenin modulates hematopoietic stem/progenitor activity via Wnt/TCF transcription (IDA); a blood-lineage developmental outcome downstream of signaling.
Reason: downstream Wnt-driven hematopoiesis
Supporting Evidence:
PMID:12717450
A role for Wnt signalling in self-renewal of haematopoietic stem cells.
GO:0030154 cell differentiation
IMP
PMID:16102745
The duality of beta-catenin function: a requirement in lens ... 		MARK AS OVER ANNOTATED
Summary: Top-level differentiation umbrella that says nothing specific about beta-catenin; its specific lineage-differentiation terms already capture the Wnt-driven roles.
Reason: vague umbrella superseded by specific terms
Supporting Evidence:
PMID:16102745
The duality of beta-catenin function: a requirement in lens morphogenesis and signaling suppression of lens fate in periocular ectoderm.
GO:0030217 T cell differentiation
IMP
PMID:14608382
Deletion of beta-catenin impairs T cell development. 		KEEP AS NON CORE
Summary: Beta-catenin modulates thymocyte/T-cell differentiation through Wnt/TCF target-gene activation; an immune-lineage developmental outcome, not its proximal adhesion or transcriptional mechanism.
Reason: downstream of Wnt/TCF program in lymphoid lineage
Supporting Evidence:
PMID:14608382
Deletion of beta-catenin impairs T cell development.
GO:0030316 osteoclast differentiation
IMP
PMID:15866165
Canonical Wnt signaling in differentiated osteoblasts contro... 		KEEP AS NON CORE
Summary: Beta-catenin indirectly shapes osteoclast differentiation through osteoblast-derived RANKL/OPG balance; a downstream bone phenotype.
Reason: Osteoclast differentiation downstream of Wnt-controlled RANKL/OPG output.
Supporting Evidence:
PMID:15866165
Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
GO:0030324 lung development
IMP
PMID:12885771
beta-Catenin is required for specification of proximal/dista... 		KEEP AS NON CORE
Summary: Beta-catenin governs lung branching and cell-fate programs through Wnt transcription; a respiratory organ-development outcome downstream of signaling.
Reason: downstream Wnt-driven lung development
Supporting Evidence:
PMID:12885771
beta-Catenin is required for specification of proximal/distal cell fate during lung morphogenesis.
GO:0048709 oligodendrocyte differentiation
IMP
PMID:19503085
HDAC1 and HDAC2 regulate oligodendrocyte differentiation by ... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling modulates oligodendrocyte lineage progression; the differentiation process is downstream of its transcription.
Reason: Glial differentiation downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:19503085
HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction.
GO:0051450 myoblast proliferation
IMP
PMID:18231602
Formation and differentiation of multiple mesenchymal lineag... 		KEEP AS NON CORE
Summary: Wnt/beta-catenin signaling promotes myoblast expansion during myogenesis; this proliferative phenotype is a downstream consequence of its transcriptional output.
Reason: Myogenic proliferation downstream of beta-catenin Wnt-target transcription.
Supporting Evidence:
PMID:18231602
Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
GO:0060441 epithelial tube branching involved in lung morphogenesis
IMP
PMID:18533146
An FGF-WNT gene regulatory network controls lung mesenchyme ... 		KEEP AS NON CORE
Summary: Beta-catenin drives lung airway branching through Wnt-driven epithelial-mesenchymal programs; a pulmonary morphogenetic outcome, not core function.
Reason: downstream Wnt-driven lung branching
Supporting Evidence:
PMID:18533146
An FGF-WNT gene regulatory network controls lung mesenchyme development.
GO:0060487 lung epithelial cell differentiation
IMP
PMID:16040629
Beta-catenin regulates differentiation of respiratory epithe... 		KEEP AS NON CORE
Summary: Beta-catenin specifies lung epithelial cell types via Wnt/TCF transcription; an airway cell-fate outcome downstream of signaling.
Reason: downstream Wnt-driven lung epithelial fate
Supporting Evidence:
PMID:16040629
Beta-catenin regulates differentiation of respiratory epithelial cells in vivo.
GO:0060767 epithelial cell proliferation involved in prostate gland development
IMP
PMID:12813461
Activation of beta-catenin in prostate epithelium induces hy... 		KEEP AS NON CORE
Summary: Beta-catenin promotes prostate epithelial proliferation via Wnt target genes; a tissue-specific growth outcome downstream of its transcriptional role.
Reason: downstream Wnt-driven prostate epithelial proliferation
Supporting Evidence:
PMID:12813461
Activation of beta-catenin in prostate epithelium induces hyperplasias and squamous transdifferentiation.
GO:0072089 stem cell proliferation
IMP
PMID:18533146
An FGF-WNT gene regulatory network controls lung mesenchyme ... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling sustains stem/progenitor self-renewal and proliferation across tissues; a key downstream consequence of its transcriptional program.
Reason: Stem-cell proliferation/maintenance downstream of Wnt transcription.
Supporting Evidence:
PMID:18533146
An FGF-WNT gene regulatory network controls lung mesenchyme development.
GO:0097190 apoptotic signaling pathway
IMP
PMID:15131783
Inducible Cre-mediated control of gene expression in the mur... 		KEEP AS NON CORE
Summary: Beta-catenin influences apoptotic signaling indirectly via Wnt target genes (e.g. survival genes); a cell-fate consequence, not a direct apoptotic mechanism.
Reason: indirect, downstream of Wnt survival-gene program
Supporting Evidence:
PMID:15131783
Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin.
GO:0097190 apoptotic signaling pathway
IMP
PMID:20454446
WNT4/beta-catenin pathway maintains female germ cell surviva... 		KEEP AS NON CORE
Summary: Beta-catenin influences apoptotic signaling indirectly via Wnt target genes (e.g. survival genes); a cell-fate consequence, not a direct apoptotic mechanism.
Reason: indirect, downstream of Wnt survival-gene program
Supporting Evidence:
PMID:20454446
WNT4/beta-catenin pathway maintains female germ cell survival by inhibiting activin betaB in the mouse fetal ovary.
GO:0097190 apoptotic signaling pathway
IGI
PMID:20454446
WNT4/beta-catenin pathway maintains female germ cell surviva... 		KEEP AS NON CORE
Summary: Beta-catenin influences apoptotic signaling indirectly via Wnt target genes (e.g. survival genes); a cell-fate consequence, not a direct apoptotic mechanism.
Reason: indirect, downstream of Wnt survival-gene program
Supporting Evidence:
PMID:20454446
WNT4/beta-catenin pathway maintains female germ cell survival by inhibiting activin betaB in the mouse fetal ovary.
GO:0032212 positive regulation of telomere maintenance via telomerase
IMP
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells a... 		KEEP AS NON CORE
Summary: Beta-catenin up-regulates Tert transcription, boosting telomerase activity; a downstream transcriptional-target effect rather than a direct enzymatic role.
Reason: Telomerase upregulation downstream of beta-catenin Tert transcription.
Supporting Evidence:
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
GO:0001222 transcription corepressor binding
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Binding to corepressors (e.g. via ICAT/Groucho crosstalk) modulates Wnt output, a regulatory rather than core coactivation interaction.
Reason: Regulatory partner; electronic, non-core.
GO:0016358 dendrite development
IGI
PMID:27713508
Conditional Knockout of Breast Carcinoma Amplified Sequence ... 		KEEP AS NON CORE
Summary: Beta-catenin influences dendrite development through synaptic/adhesion roles in neurons, a tissue-specific developmental process.
Reason: Neuronal developmental role; IGI, non-core.
Supporting Evidence:
PMID:27713508
Conditional Knockout of Breast Carcinoma Amplified Sequence 2 (BCAS2) in Mouse Forebrain Causes Dendritic Malformation via Ξ²-catenin.
GO:0001222 transcription corepressor binding
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Binding to corepressors (e.g. via ICAT/Groucho crosstalk) modulates Wnt output, a regulatory rather than core coactivation interaction.
Reason: Regulatory partner; electronic, non-core.
GO:0060856 establishment of blood-brain barrier
IMP
PMID:25083995
Canonical WNT signaling components in vascular development a... 		KEEP AS NON CORE
Summary: Beta-catenin (Wnt7-driven) establishes BBB endothelial properties via TCF transcription and junctions; a neurovascular barrier outcome downstream of its dual role.
Reason: downstream Wnt/junction-driven BBB formation
Supporting Evidence:
PMID:25083995
Canonical WNT signaling components in vascular development and barrier formation.
GO:1990963 establishment of blood-retinal barrier
IMP
PMID:25083995
Canonical WNT signaling components in vascular development a... 		KEEP AS NON CORE
Summary: Beta-catenin (Norrin/Wnt-driven) establishes the blood-retinal barrier via TCF transcription and junctional integrity; a barrier-formation outcome downstream of its dual role.
Reason: downstream Wnt/junction-driven BRB formation
Supporting Evidence:
PMID:25083995
Canonical WNT signaling components in vascular development and barrier formation.
GO:0001709 cell fate determination
IMP
PMID:15708565
Effects of canonical Wnt signaling on dorso-ventral specific... 		KEEP AS NON CORE
Summary: Beta-catenin biases cell-fate determination by activating Wnt/TCF lineage genes; a developmental fate outcome downstream of its transcriptional role.
Reason: downstream Wnt-driven fate determination
Supporting Evidence:
PMID:15708565
Effects of canonical Wnt signaling on dorso-ventral specification of the mouse telencephalon.
GO:0003682 chromatin binding
IDA
PMID:15024079
Brn-2 expression controls melanoma proliferation and is dire... 		ACCEPT
Summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
Reason: Core nuclear Wnt role; IDA/IGI-supported.
Supporting Evidence:
PMID:15024079
Brn-2 expression controls melanoma proliferation and is directly regulated by beta-catenin.
GO:0003682 chromatin binding
IDA
PMID:15778706
Wnt signalling induces maturation of Paneth cells in intesti... 		ACCEPT
Summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
Reason: Core nuclear Wnt role; IDA/IGI-supported.
Supporting Evidence:
PMID:15778706
Wnt signalling induces maturation of Paneth cells in intestinal crypts.
GO:0003682 chromatin binding
IDA
PMID:15907834
Wnt/beta-catenin signaling acts upstream of N-myc, BMP4, and... 		ACCEPT
Summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
Reason: Core nuclear Wnt role; IDA/IGI-supported.
Supporting Evidence:
PMID:15907834
Wnt/beta-catenin signaling acts upstream of N-myc, BMP4, and FGF signaling to regulate proximal-distal patterning in the lung.
GO:0003682 chromatin binding
IDA
PMID:16581771
CCN1/Cyr61 is regulated by the canonical Wnt signal and play... 		ACCEPT
Summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
Reason: Core nuclear Wnt role; IDA/IGI-supported.
Supporting Evidence:
PMID:16581771
CCN1/Cyr61 is regulated by the canonical Wnt signal and plays an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells.
GO:0030154 cell differentiation
IMP
PMID:15131783
Inducible Cre-mediated control of gene expression in the mur... 		MARK AS OVER ANNOTATED
Summary: Top-level differentiation umbrella that says nothing specific about beta-catenin; its specific lineage-differentiation terms already capture the Wnt-driven roles.
Reason: vague umbrella superseded by specific terms
Supporting Evidence:
PMID:15131783
Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin.
GO:0030154 cell differentiation
IMP
PMID:16192304
Beta-catenin is essential for pancreatic acinar but not isle... 		MARK AS OVER ANNOTATED
Summary: Top-level differentiation umbrella that says nothing specific about beta-catenin; its specific lineage-differentiation terms already capture the Wnt-driven roles.
Reason: vague umbrella superseded by specific terms
Supporting Evidence:
PMID:16192304
Beta-catenin is essential for pancreatic acinar but not islet development.
GO:0030324 lung development
IMP
PMID:18231602
Formation and differentiation of multiple mesenchymal lineag... 		KEEP AS NON CORE
Summary: Beta-catenin governs lung branching and cell-fate programs through Wnt transcription; a respiratory organ-development outcome downstream of signaling.
Reason: downstream Wnt-driven lung development
Supporting Evidence:
PMID:18231602
Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
GO:0030539 male genitalia development
IMP
PMID:19282366
Genetic interactions of the androgen and Wnt/beta-catenin pa... 		KEEP AS NON CORE
Summary: Beta-catenin drives male external genital outgrowth/patterning via Wnt transcription; a urogenital developmental outcome downstream of signaling.
Reason: downstream Wnt-driven male genitalia development
Supporting Evidence:
PMID:19282366
Genetic interactions of the androgen and Wnt/beta-catenin pathways for the masculinization of external genitalia.
GO:0030856 regulation of epithelial cell differentiation
IMP
PMID:12813461
Activation of beta-catenin in prostate epithelium induces hy... 		KEEP AS NON CORE
Summary: Generic epithelial-differentiation regulation reflects beta-catenin's Wnt control of epithelial fate; a downstream umbrella process.
Reason: Epithelial fate regulation downstream of Wnt transcription.
Supporting Evidence:
PMID:12813461
Activation of beta-catenin in prostate epithelium induces hyperplasias and squamous transdifferentiation.
GO:0030858 positive regulation of epithelial cell differentiation
IMP
PMID:16040629
Beta-catenin regulates differentiation of respiratory epithe... 		KEEP AS NON CORE
Summary: Beta-catenin promotes epithelial differentiation in several tissues via Wnt-target transcription; a downstream lineage phenotype.
Reason: Epithelial differentiation downstream of Wnt transcription.
Supporting Evidence:
PMID:16040629
Beta-catenin regulates differentiation of respiratory epithelial cells in vivo.
GO:0030900 forebrain development
IMP
PMID:15708565
Effects of canonical Wnt signaling on dorso-ventral specific... 		KEEP AS NON CORE
Summary: Beta-catenin patterns forebrain via Wnt/TCF neural transcription and progenitor control; a CNS developmental outcome, not core function.
Reason: downstream Wnt-driven forebrain development
Supporting Evidence:
PMID:15708565
Effects of canonical Wnt signaling on dorso-ventral specification of the mouse telencephalon.
GO:0031016 pancreas development
IMP
PMID:16192304
Beta-catenin is essential for pancreatic acinar but not isle... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling is required for pancreatic growth and acinar development; a downstream organ-development phenotype.
Reason: Pancreas development downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:16192304
Beta-catenin is essential for pancreatic acinar but not islet development.
GO:0031069 hair follicle morphogenesis
IMP
PMID:11371349
beta-Catenin controls hair follicle morphogenesis and stem c... 		KEEP AS NON CORE
Summary: Beta-catenin is essential for hair-follicle morphogenesis through epidermal Wnt/TCF transcription; an ectodermal appendage outcome downstream of signaling.
Reason: downstream Wnt-driven hair follicle morphogenesis
Supporting Evidence:
PMID:11371349
beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin.
GO:0031069 hair follicle morphogenesis
IMP
PMID:24309208
Wnt/Ξ²-catenin signaling in dermal condensates is required fo... 		KEEP AS NON CORE
Summary: Beta-catenin is essential for hair-follicle morphogenesis through epidermal Wnt/TCF transcription; an ectodermal appendage outcome downstream of signaling.
Reason: downstream Wnt-driven hair follicle morphogenesis
Supporting Evidence:
PMID:24309208
Wnt/Ξ²-catenin signaling in dermal condensates is required for hair follicle formation.
GO:0031641 regulation of myelination
IMP
PMID:19515974
Dysregulation of the Wnt pathway inhibits timely myelination... 		KEEP AS NON CORE
Summary: Beta-catenin modulates myelination via Wnt-dependent control of oligodendrocyte maturation; a downstream glial/CNS phenotype.
Reason: Myelination control downstream of Wnt oligodendrocyte transcription.
Supporting Evidence:
PMID:19515974
Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS.
GO:0032331 negative regulation of chondrocyte differentiation
IGI
PMID:16818445
Wnt9a signaling is required for joint integrity and regulati... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling biases skeletal progenitors away from chondrogenesis toward osteogenesis; a genetic-interaction downstream skeletal phenotype.
Reason: Chondrocyte suppression downstream of Wnt fate-switch transcription.
Supporting Evidence:
PMID:16818445
Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis.
GO:0033077 T cell differentiation in thymus
IMP
PMID:16025118
Loss of adenomatous polyposis coli gene function disrupts th... 		KEEP AS NON CORE
Summary: Thymic T-cell differentiation requires Wnt/beta-catenin transcriptional signaling; a tissue-specific lymphoid maturation phenotype downstream of TCF co-activation.
Reason: tissue-specific downstream Wnt output in thymus
Supporting Evidence:
PMID:16025118
Loss of adenomatous polyposis coli gene function disrupts thymic development.
GO:0034332 adherens junction organization
IMP
PMID:19129494
Wnt/beta-catenin signaling is required for CNS, but not non-... 		ACCEPT
Summary: Beta-catenin organizes adherens junctions through the cadherin-catenin complex; loss perturbs junction integrity.
Reason: Core adhesion process; IMP-supported.
Supporting Evidence:
PMID:19129494
Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis.
GO:0035050 embryonic heart tube development
IMP
PMID:18231602
Formation and differentiation of multiple mesenchymal lineag... 		KEEP AS NON CORE
Summary: Beta-catenin contributes to heart-tube formation via Wnt-driven cardiac progenitor programs; a cardiac developmental outcome, not core function.
Reason: downstream Wnt-driven heart tube development
Supporting Evidence:
PMID:18231602
Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
GO:0035112 genitalia morphogenesis
IMP
PMID:18635608
Tissue-specific requirements of beta-catenin in external gen... 		KEEP AS NON CORE
Summary: Beta-catenin shapes external genitalia via Wnt-driven outgrowth and patterning; a urogenital morphogenetic outcome downstream of transcription.
Reason: downstream Wnt-driven genital morphogenesis
Supporting Evidence:
PMID:18635608
Tissue-specific requirements of beta-catenin in external genitalia development.
GO:0035115 embryonic forelimb morphogenesis
IDA
PMID:15371327
Wnt/beta-catenin signaling is sufficient and necessary for s... 		KEEP AS NON CORE
Summary: Beta-catenin drives forelimb outgrowth/patterning through Wnt-driven AER maintenance (IDA); a limb developmental outcome downstream of its signaling role.
Reason: downstream Wnt-driven forelimb morphogenesis
Supporting Evidence:
PMID:15371327
Wnt/beta-catenin signaling is sufficient and necessary for synovial joint formation.
GO:0035116 embryonic hindlimb morphogenesis
IMP
PMID:12923052
Genetic interaction between Wnt/beta-catenin and BMP recepto... 		KEEP AS NON CORE
Summary: Beta-catenin drives hindlimb outgrowth/patterning via Wnt signaling in limb mesenchyme/AER; a limb morphogenetic outcome downstream of transcription.
Reason: downstream Wnt-driven hindlimb morphogenesis
Supporting Evidence:
PMID:12923052
Genetic interaction between Wnt/beta-catenin and BMP receptor signaling during formation of the AER and the dorsal-ventral axis in the limb.
GO:0035116 embryonic hindlimb morphogenesis
IMP
PMID:18231602
Formation and differentiation of multiple mesenchymal lineag... 		KEEP AS NON CORE
Summary: Beta-catenin drives hindlimb outgrowth/patterning via Wnt signaling in limb mesenchyme/AER; a limb morphogenetic outcome downstream of transcription.
Reason: downstream Wnt-driven hindlimb morphogenesis
Supporting Evidence:
PMID:18231602
Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
GO:0042127 regulation of cell population proliferation
IDA
PMID:12235125
Beta-catenin-induced melanoma growth requires the downstream... 		KEEP AS NON CORE
Summary: Generic proliferation regulation reflects beta-catenin's Wnt mitogenic transcriptional program; downstream and non-specific.
Reason: Umbrella proliferation regulation downstream of Wnt transcription.
Supporting Evidence:
PMID:12235125
Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor.
GO:0042127 regulation of cell population proliferation
IMP
PMID:17055474
The stabilization of beta-catenin leads to impaired primordi... 		KEEP AS NON CORE
Summary: Generic proliferation regulation reflects beta-catenin's Wnt mitogenic transcriptional program; downstream and non-specific.
Reason: Umbrella proliferation regulation downstream of Wnt transcription.
Supporting Evidence:
PMID:17055474
The stabilization of beta-catenin leads to impaired primordial germ cell development via aberrant cell cycle progression.
GO:0042127 regulation of cell population proliferation
IMP
PMID:18635608
Tissue-specific requirements of beta-catenin in external gen... 		KEEP AS NON CORE
Summary: Generic proliferation regulation reflects beta-catenin's Wnt mitogenic transcriptional program; downstream and non-specific.
Reason: Umbrella proliferation regulation downstream of Wnt transcription.
Supporting Evidence:
PMID:18635608
Tissue-specific requirements of beta-catenin in external genitalia development.
GO:0042129 regulation of T cell proliferation
IMP
PMID:14608382
Deletion of beta-catenin impairs T cell development. 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling modulates T-cell expansion during lymphopoiesis; a downstream immune-development phenotype.
Reason: T-cell proliferation control downstream of Wnt transcription.
Supporting Evidence:
PMID:14608382
Deletion of beta-catenin impairs T cell development.
GO:0042475 odontogenesis of dentin-containing tooth
IMP
PMID:15866165
Canonical Wnt signaling in differentiated osteoblasts contro... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling is essential for tooth morphogenesis and dentinogenesis; a downstream organ-development phenotype.
Reason: Tooth development downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:15866165
Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
GO:0042733 embryonic digit morphogenesis
IMP
PMID:12923052
Genetic interaction between Wnt/beta-catenin and BMP recepto... 		KEEP AS NON CORE
Summary: Beta-catenin shapes digit formation in the limb through Wnt-driven AER and mesenchymal programs; a limb morphogenetic outcome downstream of signaling.
Reason: downstream Wnt-driven digit morphogenesis
Supporting Evidence:
PMID:12923052
Genetic interaction between Wnt/beta-catenin and BMP receptor signaling during formation of the AER and the dorsal-ventral axis in the limb.
GO:0042733 embryonic digit morphogenesis
IMP
PMID:20043884
Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling wit... 		KEEP AS NON CORE
Summary: Beta-catenin shapes digit formation in the limb through Wnt-driven AER and mesenchymal programs; a limb morphogenetic outcome downstream of signaling.
Reason: downstream Wnt-driven digit morphogenesis
Supporting Evidence:
PMID:20043884
Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling within the Apical Ectodermal Ridge (AER) regulates interdigit formation.
GO:0042733 embryonic digit morphogenesis
IGI
PMID:20043884
Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling wit... 		KEEP AS NON CORE
Summary: Beta-catenin shapes digit formation in the limb through Wnt-driven AER and mesenchymal programs; a limb morphogenetic outcome downstream of signaling.
Reason: downstream Wnt-driven digit morphogenesis
Supporting Evidence:
PMID:20043884
Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling within the Apical Ectodermal Ridge (AER) regulates interdigit formation.
GO:0042981 regulation of apoptotic process
IMP
PMID:20043884
Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling wit... 		KEEP AS NON CORE
Summary: Generic apoptosis regulation reflects beta-catenin's transcriptional control of survival/death genes; a downstream, non-specific regulatory role.
Reason: Umbrella survival/death regulation downstream of Wnt transcription.
Supporting Evidence:
PMID:20043884
Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling within the Apical Ectodermal Ridge (AER) regulates interdigit formation.
GO:0043410 positive regulation of MAPK cascade
IGI
PMID:16478791
APC inhibits ERK pathway activation and cellular proliferati... 		KEEP AS NON CORE
Summary: IGI-supported genetic interaction with MAPK signaling; a crosstalk effect rather than beta-catenin's core Wnt/transcription function.
Reason: Crosstalk regulatory effect; non-core (experimental IGI, not removed).
Supporting Evidence:
PMID:16478791
APC inhibits ERK pathway activation and cellular proliferation induced by RAS.
GO:0043524 negative regulation of neuron apoptotic process
IGI
PMID:22956852
Integration of Ξ²-catenin, sirtuin, and FOXO signaling protec... 		KEEP AS NON CORE
Summary: Beta-catenin protects neurons from apoptosis in genetic-interaction assays, consistent with Wnt-driven survival transcription; a neuron-specific downstream phenotype.
Reason: Neuronal survival downstream of Wnt/beta-catenin transcriptional targets.
Supporting Evidence:
PMID:22956852
Integration of Ξ²-catenin, sirtuin, and FOXO signaling protects from mutant huntingtin toxicity.
GO:0043588 skin development
IMP
PMID:19718027
Tcf3 and Tcf4 are essential for long-term homeostasis of ski... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling governs epidermal/appendage development; a downstream organ-system phenotype combining adhesion and transcription roles.
Reason: Skin development downstream of Wnt transcription and adhesion.
Supporting Evidence:
PMID:19718027
Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia.
GO:0045453 bone resorption
IMP
PMID:15866165
Canonical Wnt signaling in differentiated osteoblasts contro... 		KEEP AS NON CORE
Summary: Beta-catenin shifts osteoblast/osteoclast balance (e.g. OPG induction) via Wnt/TCF transcription, regulating resorption; a skeletal-remodeling outcome, not core function.
Reason: downstream of Wnt-driven osteo-transcriptional balance
Supporting Evidence:
PMID:15866165
Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
GO:0045453 bone resorption
IGI
PMID:15866165
Canonical Wnt signaling in differentiated osteoblasts contro... 		KEEP AS NON CORE
Summary: Beta-catenin shifts osteoblast/osteoclast balance (e.g. OPG induction) via Wnt/TCF transcription, regulating resorption; a skeletal-remodeling outcome, not core function.
Reason: downstream of Wnt-driven osteo-transcriptional balance
Supporting Evidence:
PMID:15866165
Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
GO:0045595 regulation of cell differentiation
IDA
PMID:12717450
A role for Wnt signalling in self-renewal of haematopoietic ... 		KEEP AS NON CORE
Summary: IDA-level generic differentiation regulation summarizes beta-catenin's transcriptional control of many fate decisions; a downstream umbrella process.
Reason: Broad differentiation control downstream of Wnt transcription.
Supporting Evidence:
PMID:12717450
A role for Wnt signalling in self-renewal of haematopoietic stem cells.
GO:0045596 negative regulation of cell differentiation
IMP
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts fr... 		KEEP AS NON CORE
Summary: Beta-catenin can hold progenitors undifferentiated via Wnt-target transcription (stemness genes); a broad downstream differentiation-blocking phenotype.
Reason: Differentiation suppression downstream of Wnt stemness-gene transcription.
Supporting Evidence:
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
GO:0045596 negative regulation of cell differentiation
IMP
PMID:16102745
The duality of beta-catenin function: a requirement in lens ... 		KEEP AS NON CORE
Summary: Beta-catenin can hold progenitors undifferentiated via Wnt-target transcription (stemness genes); a broad downstream differentiation-blocking phenotype.
Reason: Differentiation suppression downstream of Wnt stemness-gene transcription.
Supporting Evidence:
PMID:16102745
The duality of beta-catenin function: a requirement in lens morphogenesis and signaling suppression of lens fate in periocular ectoderm.
GO:0045603 positive regulation of endothelial cell differentiation
IMP
PMID:18231602
Formation and differentiation of multiple mesenchymal lineag... 		KEEP AS NON CORE
Summary: Wnt/beta-catenin transcription supports endothelial cell fate during vascular development; the differentiation outcome is downstream.
Reason: Endothelial differentiation downstream of Wnt-target transcription.
Supporting Evidence:
PMID:18231602
Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
GO:0045667 regulation of osteoblast differentiation
IMP
PMID:15576404
Sequential roles of Hedgehog and Wnt signaling in osteoblast... 		KEEP AS NON CORE
Summary: Generic osteoblast-differentiation regulation summarizes beta-catenin's Wnt control of bone-forming cell fate; downstream and somewhat redundant.
Reason: Osteoblast fate regulation downstream of Wnt transcription.
Supporting Evidence:
PMID:15576404
Sequential roles of Hedgehog and Wnt signaling in osteoblast development.
GO:0045667 regulation of osteoblast differentiation
IMP
PMID:15802266
Essential role of beta-catenin in postnatal bone acquisition... 		KEEP AS NON CORE
Summary: Generic osteoblast-differentiation regulation summarizes beta-catenin's Wnt control of bone-forming cell fate; downstream and somewhat redundant.
Reason: Osteoblast fate regulation downstream of Wnt transcription.
Supporting Evidence:
PMID:15802266
Essential role of beta-catenin in postnatal bone acquisition.
GO:0045669 positive regulation of osteoblast differentiation
IMP
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts fr... 		KEEP AS NON CORE
Summary: Beta-catenin promotes osteoblast differentiation by activating osteogenic Wnt targets; a downstream, lineage-specific developmental role.
Reason: Pro-osteoblast effect downstream of Wnt osteogenic transcription.
Supporting Evidence:
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
GO:0045670 regulation of osteoclast differentiation
IMP
PMID:15802266
Essential role of beta-catenin in postnatal bone acquisition... 		KEEP AS NON CORE
Summary: Beta-catenin regulates osteoclastogenesis indirectly via osteoblast RANKL/OPG transcription; a downstream bone-remodeling control.
Reason: Osteoclast regulation downstream of Wnt-driven osteoblast signaling.
Supporting Evidence:
PMID:15802266
Essential role of beta-catenin in postnatal bone acquisition.
GO:0045671 negative regulation of osteoclast differentiation
IMP
PMID:15866165
Canonical Wnt signaling in differentiated osteoblasts contro... 		KEEP AS NON CORE
Summary: Osteoblast-lineage beta-catenin Wnt signaling raises OPG to restrain osteoclastogenesis; a downstream bone-remodeling phenotype.
Reason: Osteoclast suppression downstream of Wnt-driven OPG transcription.
Supporting Evidence:
PMID:15866165
Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
GO:0045743 positive regulation of fibroblast growth factor receptor signaling pathway
IMP
PMID:18231602
Formation and differentiation of multiple mesenchymal lineag... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt output can up-regulate FGF ligands/receptors, amplifying FGFR signaling; a downstream signaling-crosstalk phenotype.
Reason: FGFR pathway boost downstream of Wnt-target transcription.
Supporting Evidence:
PMID:18231602
Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
GO:0045743 positive regulation of fibroblast growth factor receptor signaling pathway
IMP
PMID:18533146
An FGF-WNT gene regulatory network controls lung mesenchyme ... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt output can up-regulate FGF ligands/receptors, amplifying FGFR signaling; a downstream signaling-crosstalk phenotype.
Reason: FGFR pathway boost downstream of Wnt-target transcription.
Supporting Evidence:
PMID:18533146
An FGF-WNT gene regulatory network controls lung mesenchyme development.
GO:0045892 negative regulation of DNA-templated transcription
IDA
PMID:12551949
Lymphoid enhancer factor-1 and beta-catenin inhibit Runx2-de... 		KEEP AS NON CORE
Summary: beta-catenin can repress specific targets (e.g. via SOX9/TCF competition or unliganded-TCF contexts), but its core, defining transcriptional role is positive coactivation of TCF/LEF targets.
Reason: Context-dependent repression; secondary to its activating role.
Supporting Evidence:
PMID:12551949
Lymphoid enhancer factor-1 and beta-catenin inhibit Runx2-dependent transcriptional activation of the osteocalcin promoter.
GO:0045892 negative regulation of DNA-templated transcription
IMP
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts fr... 		KEEP AS NON CORE
Summary: beta-catenin can repress specific targets (e.g. via SOX9/TCF competition or unliganded-TCF contexts), but its core, defining transcriptional role is positive coactivation of TCF/LEF targets.
Reason: Context-dependent repression; secondary to its activating role.
Supporting Evidence:
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
GO:0045893 positive regulation of DNA-templated transcription
IDA
PMID:10631168
Hippocampus development and generation of dentate gyrus gran... 		MODIFY
Summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
Reason: Generic parent; specialize to Pol II-specific positive regulation.
Supporting Evidence:
PMID:10631168
Hippocampus development and generation of dentate gyrus granule cells is regulated by LEF1.
GO:0045893 positive regulation of DNA-templated transcription
IDA
PMID:12551949
Lymphoid enhancer factor-1 and beta-catenin inhibit Runx2-de... 		MODIFY
Summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
Reason: Generic parent; specialize to Pol II-specific positive regulation.
Supporting Evidence:
PMID:12551949
Lymphoid enhancer factor-1 and beta-catenin inhibit Runx2-dependent transcriptional activation of the osteocalcin promoter.
GO:0045893 positive regulation of DNA-templated transcription
IMP
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts fr... 		MODIFY
Summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
Reason: Generic parent; specialize to Pol II-specific positive regulation.
Supporting Evidence:
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
GO:0045893 positive regulation of DNA-templated transcription
IDA
PMID:16936075
The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 exp... 		MODIFY
Summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
Reason: Generic parent; specialize to Pol II-specific positive regulation.
Supporting Evidence:
PMID:16936075
The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 expression during somitogenesis.
GO:0045893 positive regulation of DNA-templated transcription
IMP
PMID:17767158
Modulation of morphogenesis by noncanonical Wnt signaling re... 		MODIFY
Summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
Reason: Generic parent; specialize to Pol II-specific positive regulation.
Supporting Evidence:
PMID:17767158
Modulation of morphogenesis by noncanonical Wnt signaling requires ATF/CREB family-mediated transcriptional activation of TGFbeta2.
GO:0045893 positive regulation of DNA-templated transcription
IDA
PMID:19056892
A functional link between Wnt signaling and SKP2-independent... 		MODIFY
Summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
Reason: Generic parent; specialize to Pol II-specific positive regulation.
Supporting Evidence:
PMID:19056892
A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors.
GO:0045893 positive regulation of DNA-templated transcription
IMP
PMID:19690384
Wnt signaling regulates smooth muscle precursor development ... 		MODIFY
Summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
Reason: Generic parent; specialize to Pol II-specific positive regulation.
Supporting Evidence:
PMID:19690384
Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.
GO:0045944 positive regulation of transcription by RNA polymerase II
IMP
PMID:15024079
Brn-2 expression controls melanoma proliferation and is dire... 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
Supporting Evidence:
PMID:15024079
Brn-2 expression controls melanoma proliferation and is directly regulated by beta-catenin.
GO:0045944 positive regulation of transcription by RNA polymerase II
IGI
PMID:15729346
Pax3 functions at a nodal point in melanocyte stem cell diff... 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
Supporting Evidence:
PMID:15729346
Pax3 functions at a nodal point in melanocyte stem cell differentiation.
GO:0045944 positive regulation of transcription by RNA polymerase II
IGI
PMID:15778706
Wnt signalling induces maturation of Paneth cells in intesti... 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
Supporting Evidence:
PMID:15778706
Wnt signalling induces maturation of Paneth cells in intestinal crypts.
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:15907834
Wnt/beta-catenin signaling acts upstream of N-myc, BMP4, and... 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
Supporting Evidence:
PMID:15907834
Wnt/beta-catenin signaling acts upstream of N-myc, BMP4, and FGF signaling to regulate proximal-distal patterning in the lung.
GO:0045944 positive regulation of transcription by RNA polymerase II
IGI
PMID:16678101
Homeodomain-mediated beta-catenin-dependent switching events... 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
Supporting Evidence:
PMID:16678101
Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:19620969
A regulatory pathway involving Notch1/beta-catenin/Isl1 dete... 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
Supporting Evidence:
PMID:19620969
A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate.
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:20159597
Characterization and in vivo pharmacological rescue of a Wnt... 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
Supporting Evidence:
PMID:20159597
Characterization and in vivo pharmacological rescue of a Wnt2-Gata6 pathway required for cardiac inflow tract development.
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:20627076
The Wnt/beta-catenin pathway modulates vascular remodeling a... 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
Supporting Evidence:
PMID:20627076
The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/Notch signaling.
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:21750544
The Wnt3a/Ξ²-catenin target gene Mesogenin1 controls the segm... 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
Supporting Evidence:
PMID:21750544
The Wnt3a/Ξ²-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program.
GO:0048469 cell maturation
IMP
PMID:15576404
Sequential roles of Hedgehog and Wnt signaling in osteoblast... 		KEEP AS NON CORE
Summary: Beta-catenin supports terminal cell maturation in several lineages through Wnt transcriptional output; a differentiation-completion outcome (IDA/IMP), not core function.
Reason: downstream maturation of Wnt-target lineages
Supporting Evidence:
PMID:15576404
Sequential roles of Hedgehog and Wnt signaling in osteoblast development.
GO:0048469 cell maturation
IDA
PMID:17706960
Persistent expression of stabilized beta-catenin delays matu... 		KEEP AS NON CORE
Summary: Beta-catenin supports terminal cell maturation in several lineages through Wnt transcriptional output; a differentiation-completion outcome (IDA/IMP), not core function.
Reason: downstream maturation of Wnt-target lineages
Supporting Evidence:
PMID:17706960
Persistent expression of stabilized beta-catenin delays maturation of radial glial cells into intermediate progenitors.
GO:0048489 synaptic vesicle transport
IMP
PMID:14622577
Role of beta-catenin in synaptic vesicle localization and pr... 		KEEP AS NON CORE
Summary: Beta-catenin's cadherin scaffolding influences synaptic vesicle localization/transport; a downstream adhesion-linked synaptic phenotype.
Reason: Vesicle transport downstream of cadherin-adhesion scaffolding role.
Supporting Evidence:
PMID:14622577
Role of beta-catenin in synaptic vesicle localization and presynaptic assembly.
GO:0048513 animal organ development
IMP
PMID:18635608
Tissue-specific requirements of beta-catenin in external gen... 		MARK AS OVER ANNOTATED
Summary: Generic organ-development umbrella that conveys nothing specific about beta-catenin; the many specific organ terms already capture its Wnt-driven roles.
Reason: vague high-level umbrella adds no specificity
Supporting Evidence:
PMID:18635608
Tissue-specific requirements of beta-catenin in external genitalia development.
GO:0048538 thymus development
IMP
PMID:16025118
Loss of adenomatous polyposis coli gene function disrupts th... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling supports thymic epithelial/lymphoid development; a downstream organ-development phenotype.
Reason: Thymus development downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:16025118
Loss of adenomatous polyposis coli gene function disrupts thymic development.
GO:0048599 oocyte development
IGI
PMID:20454446
WNT4/beta-catenin pathway maintains female germ cell surviva... 		KEEP AS NON CORE
Summary: Beta-catenin influences oogenesis in genetic-interaction assays, likely via Wnt-transcriptional control of follicular signaling; a downstream germ-cell phenotype.
Reason: Oocyte development downstream of Wnt transcription; non-core.
Supporting Evidence:
PMID:20454446
WNT4/beta-catenin pathway maintains female germ cell survival by inhibiting activin betaB in the mouse fetal ovary.
GO:0048617 embryonic foregut morphogenesis
IMP
PMID:18692041
Bmp4 is required for tracheal formation: a novel mouse model... 		KEEP AS NON CORE
Summary: Beta-catenin patterns foregut endoderm via Wnt/TCF transcription enabling organ budding; a gut morphogenetic outcome, not core function.
Reason: downstream Wnt-driven foregut morphogenesis
Supporting Evidence:
PMID:18692041
Bmp4 is required for tracheal formation: a novel mouse model for tracheal agenesis.
GO:0048715 negative regulation of oligodendrocyte differentiation
IMP
PMID:19503085
HDAC1 and HDAC2 regulate oligodendrocyte differentiation by ... 		KEEP AS NON CORE
Summary: Wnt/beta-catenin inhibits oligodendrocyte maturation (e.g. via Id targets); a downstream glial-fate phenotype.
Reason: Oligodendrocyte block downstream of Wnt transcriptional targets.
Supporting Evidence:
PMID:19503085
HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction.
GO:0050808 synapse organization
IMP
PMID:14622577
Role of beta-catenin in synaptic vesicle localization and pr... 		KEEP AS NON CORE
Summary: Beta-catenin organizes synapses through cadherin adhesion, a neuron-specific developmental/structural role.
Reason: Neuronal process; IMP, non-core.
Supporting Evidence:
PMID:14622577
Role of beta-catenin in synaptic vesicle localization and presynaptic assembly.
GO:0051145 smooth muscle cell differentiation
IMP
PMID:19690384
Wnt signaling regulates smooth muscle precursor development ... 		KEEP AS NON CORE
Summary: Beta-catenin contributes to smooth muscle fate specification via Wnt-driven transcription; the differentiation outcome is downstream of that program.
Reason: Smooth-muscle fate is downstream transcriptional output, not core MF.
Supporting Evidence:
PMID:19690384
Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.
GO:0060066 oviduct development
IMP
PMID:17532316
Essential roles of mesenchyme-derived beta-catenin in mouse ... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling patterns Mullerian-duct-derived oviduct; a downstream reproductive-organ development phenotype.
Reason: Oviduct development downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:17532316
Essential roles of mesenchyme-derived beta-catenin in mouse MΓΌllerian duct morphogenesis.
GO:0060070 canonical Wnt signaling pathway
IDA
PMID:12235125
Beta-catenin-induced melanoma growth requires the downstream... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:12235125
Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0060070 canonical Wnt signaling pathway
IDA
PMID:12464179
Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway m... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:12464179
Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0060070 canonical Wnt signaling pathway
IDA
PMID:12717450
A role for Wnt signalling in self-renewal of haematopoietic ... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:12717450
A role for Wnt signalling in self-renewal of haematopoietic stem cells.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0060070 canonical Wnt signaling pathway
IDA
PMID:15781477
Sox2 induction by FGF and FGFR2 activating mutations inhibit... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:15781477
Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0060070 canonical Wnt signaling pathway
IGI
PMID:16678101
Homeodomain-mediated beta-catenin-dependent switching events... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:16678101
Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0060070 canonical Wnt signaling pathway
IGI
PMID:16818445
Wnt9a signaling is required for joint integrity and regulati... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:16818445
Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0060070 canonical Wnt signaling pathway
IMP
PMID:19060336
A Wnt7b-dependent pathway regulates the orientation of epith... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:19060336
A Wnt7b-dependent pathway regulates the orientation of epithelial cell division and establishes the cortico-medullary axis of the mammalian kidney.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0060070 canonical Wnt signaling pathway
IMP
PMID:19619491
Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:19619491
Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0060070 canonical Wnt signaling pathway
IGI
PMID:19686689
Wnt2/2b and beta-catenin signaling are necessary and suffici... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:19686689
Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0060070 canonical Wnt signaling pathway
IMP
PMID:19690384
Wnt signaling regulates smooth muscle precursor development ... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:19690384
Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0060070 canonical Wnt signaling pathway
IGI
PMID:20454446
WNT4/beta-catenin pathway maintains female germ cell surviva... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:20454446
WNT4/beta-catenin pathway maintains female germ cell survival by inhibiting activin betaB in the mouse fetal ovary.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0060070 canonical Wnt signaling pathway
IDA
PMID:31222549
The Shisa3 knockout mouse exhibits normal bone phenotype. 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:31222549
The Shisa3 knockout mouse exhibits normal bone phenotype.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0060173 limb development
IMP
PMID:12569130
Ectodermal Wnt3/beta-catenin signaling is required for the e... 		KEEP AS NON CORE
Summary: Beta-catenin is required for limb-bud outgrowth via Wnt-driven AER maintenance; a limb organ-development outcome downstream of signaling.
Reason: downstream Wnt-driven limb development
Supporting Evidence:
PMID:12569130
Ectodermal Wnt3/beta-catenin signaling is required for the establishment and maintenance of the apical ectodermal ridge.
GO:0060439 trachea morphogenesis
IMP
PMID:18231602
Formation and differentiation of multiple mesenchymal lineag... 		KEEP AS NON CORE
Summary: Beta-catenin shapes tracheal morphology during foregut development via Wnt targets; a downstream organ-morphogenesis phenotype.
Reason: Trachea morphogenesis downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:18231602
Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
GO:0060439 trachea morphogenesis
IMP
PMID:18692041
Bmp4 is required for tracheal formation: a novel mouse model... 		KEEP AS NON CORE
Summary: Beta-catenin shapes tracheal morphology during foregut development via Wnt targets; a downstream organ-morphogenesis phenotype.
Reason: Trachea morphogenesis downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:18692041
Bmp4 is required for tracheal formation: a novel mouse model for tracheal agenesis.
GO:0060440 trachea formation
IMP
PMID:19805295
beta-Catenin promotes respiratory progenitor identity in mou... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling is required for tracheal tube formation; a downstream respiratory-organ morphogenesis phenotype.
Reason: Trachea formation downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:19805295
beta-Catenin promotes respiratory progenitor identity in mouse foregut.
GO:0060441 epithelial tube branching involved in lung morphogenesis
IMP
PMID:18231602
Formation and differentiation of multiple mesenchymal lineag... 		KEEP AS NON CORE
Summary: Beta-catenin drives lung airway branching through Wnt-driven epithelial-mesenchymal programs; a pulmonary morphogenetic outcome, not core function.
Reason: downstream Wnt-driven lung branching
Supporting Evidence:
PMID:18231602
Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
GO:0060479 lung cell differentiation
IMP
PMID:19805295
beta-Catenin promotes respiratory progenitor identity in mou... 		KEEP AS NON CORE
Summary: Beta-catenin drives pulmonary cell-type differentiation via Wnt/TCF transcription; a lung cell-fate outcome downstream of signaling.
Reason: downstream Wnt-driven lung cell differentiation
Supporting Evidence:
PMID:19805295
beta-Catenin promotes respiratory progenitor identity in mouse foregut.
GO:0060484 lung-associated mesenchyme development
IMP
PMID:18533146
An FGF-WNT gene regulatory network controls lung mesenchyme ... 		KEEP AS NON CORE
Summary: Beta-catenin supports pulmonary mesenchyme development via Wnt-driven transcription enabling epithelial-mesenchymal crosstalk; a tissue developmental outcome.
Reason: downstream Wnt-driven lung mesenchyme development
Supporting Evidence:
PMID:18533146
An FGF-WNT gene regulatory network controls lung mesenchyme development.
GO:0060492 lung induction
IMP
PMID:19686689
Wnt2/2b and beta-catenin signaling are necessary and suffici... 		KEEP AS NON CORE
Summary: Beta-catenin participates in initial lung specification from foregut endoderm via Wnt transcription; an early organ-induction outcome downstream of signaling.
Reason: downstream Wnt-driven lung induction
Supporting Evidence:
PMID:19686689
Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut.
GO:0060492 lung induction
IMP
PMID:19805295
beta-Catenin promotes respiratory progenitor identity in mou... 		KEEP AS NON CORE
Summary: Beta-catenin participates in initial lung specification from foregut endoderm via Wnt transcription; an early organ-induction outcome downstream of signaling.
Reason: downstream Wnt-driven lung induction
Supporting Evidence:
PMID:19805295
beta-Catenin promotes respiratory progenitor identity in mouse foregut.
GO:0060742 epithelial cell differentiation involved in prostate gland development
IMP
PMID:12813461
Activation of beta-catenin in prostate epithelium induces hy... 		KEEP AS NON CORE
Summary: Beta-catenin drives prostate epithelial differentiation via Wnt/TCF transcription; a tissue-specific cell-fate outcome downstream of signaling.
Reason: downstream Wnt-driven prostate epithelial fate
Supporting Evidence:
PMID:12813461
Activation of beta-catenin in prostate epithelium induces hyperplasias and squamous transdifferentiation.
GO:0060769 positive regulation of epithelial cell proliferation involved in prostate gland development
IMP
PMID:12813461
Activation of beta-catenin in prostate epithelium induces hy... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling drives prostate epithelial proliferation during gland development; a downstream organ-specific phenotype.
Reason: Prostate epithelial proliferation downstream of Wnt transcription.
Supporting Evidence:
PMID:12813461
Activation of beta-catenin in prostate epithelium induces hyperplasias and squamous transdifferentiation.
GO:0060789 hair follicle placode formation
IMP
PMID:11371349
beta-Catenin controls hair follicle morphogenesis and stem c... 		KEEP AS NON CORE
Summary: Beta-catenin initiates hair placodes via Wnt/TCF transcription in epidermis (IGI/IMP); an early skin-appendage outcome downstream of signaling.
Reason: downstream Wnt-driven hair placode initiation
Supporting Evidence:
PMID:11371349
beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin.
GO:0060789 hair follicle placode formation
IGI
PMID:19619491
Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-... 		KEEP AS NON CORE
Summary: Beta-catenin initiates hair placodes via Wnt/TCF transcription in epidermis (IGI/IMP); an early skin-appendage outcome downstream of signaling.
Reason: downstream Wnt-driven hair placode initiation
Supporting Evidence:
PMID:19619491
Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
GO:0060916 mesenchymal cell proliferation involved in lung development
IMP
PMID:17128274
Wnt-beta-catenin signaling initiates taste papilla developme... 		KEEP AS NON CORE
Summary: Beta-catenin sustains lung mesenchyme proliferation via Wnt transcription supporting branching; a tissue-specific growth outcome downstream of signaling.
Reason: downstream Wnt-driven lung mesenchymal proliferation
Supporting Evidence:
PMID:17128274
Wnt-beta-catenin signaling initiates taste papilla development.
GO:0060916 mesenchymal cell proliferation involved in lung development
IMP
PMID:18231602
Formation and differentiation of multiple mesenchymal lineag... 		KEEP AS NON CORE
Summary: Beta-catenin sustains lung mesenchyme proliferation via Wnt transcription supporting branching; a tissue-specific growth outcome downstream of signaling.
Reason: downstream Wnt-driven lung mesenchymal proliferation
Supporting Evidence:
PMID:18231602
Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
GO:0061047 positive regulation of branching involved in lung morphogenesis
IMP
PMID:18533146
An FGF-WNT gene regulatory network controls lung mesenchyme ... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling promotes airway branching during lung morphogenesis; a downstream organ-morphogenesis phenotype.
Reason: Lung branching downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:18533146
An FGF-WNT gene regulatory network controls lung mesenchyme development.
GO:0061198 fungiform papilla formation
IMP
PMID:17128274
Wnt-beta-catenin signaling initiates taste papilla developme... 		KEEP AS NON CORE
Summary: Beta-catenin drives fungiform (taste) papilla formation through Wnt-driven placode programs; an ectodermal appendage outcome downstream of signaling.
Reason: downstream Wnt-driven papilla placode formation
Supporting Evidence:
PMID:17128274
Wnt-beta-catenin signaling initiates taste papilla development.
GO:0072033 renal vesicle formation
IMP
PMID:17537789
Wnt/beta-catenin signaling regulates nephron induction durin... 		KEEP AS NON CORE
Summary: Wnt/beta-catenin induces renal vesicles from cap mesenchyme, the first epithelial nephron unit; a downstream renal morphogenesis step.
Reason: Renal vesicle induction downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:17537789
Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development.
GO:0072053 renal inner medulla development
IMP
PMID:19060336
A Wnt7b-dependent pathway regulates the orientation of epith... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling contributes to inner medullary patterning during kidney development; a downstream regional renal phenotype.
Reason: Inner-medulla development downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:19060336
A Wnt7b-dependent pathway regulates the orientation of epithelial cell division and establishes the cortico-medullary axis of the mammalian kidney.
GO:0072054 renal outer medulla development
IMP
PMID:19060336
A Wnt7b-dependent pathway regulates the orientation of epith... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling shapes outer medullary kidney architecture; a downstream regional renal-development phenotype.
Reason: Outer-medulla development downstream of Wnt transcription.
Supporting Evidence:
PMID:19060336
A Wnt7b-dependent pathway regulates the orientation of epithelial cell division and establishes the cortico-medullary axis of the mammalian kidney.
GO:0072079 nephron tubule formation
IMP
PMID:17537789
Wnt/beta-catenin signaling regulates nephron induction durin... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling drives mesenchyme-to-nephron-tubule conversion; a downstream renal morphogenesis phenotype.
Reason: Nephron tubule formation downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:17537789
Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development.
GO:0098609 cell-cell adhesion
IMP
PMID:16102745
The duality of beta-catenin function: a requirement in lens ... 		ACCEPT
Summary: Beta-catenin is essential for cadherin-based cell-cell adhesion, anchoring the adhesion complex to the cytoskeleton.
Reason: Core adhesion process; IBA/IMP-supported.
Supporting Evidence:
PMID:16102745
The duality of beta-catenin function: a requirement in lens morphogenesis and signaling suppression of lens fate in periocular ectoderm.
GO:2000017 positive regulation of determination of dorsal identity
IDA
PMID:18316368
Protein encoded by the Axin(Fu) allele effectively down-regu... 		KEEP AS NON CORE
Summary: Nuclear beta-catenin specifies dorsal/organizer identity in early embryos via Wnt-target transcription; an IDA axis-patterning phenotype downstream of signaling.
Reason: Dorsal-axis specification downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:18316368
Protein encoded by the Axin(Fu) allele effectively down-regulates Wnt signaling but exerts a dominant negative effect on c-Jun N-terminal kinase signaling.
GO:2001234 negative regulation of apoptotic signaling pathway
IMP
PMID:15131783
Inducible Cre-mediated control of gene expression in the mur... 		KEEP AS NON CORE
Summary: Genetic evidence links beta-catenin to dampening apoptotic signaling, plausibly via Wnt survival-gene transcription; a downstream regulatory phenotype.
Reason: Downstream survival-signaling modulation via Wnt transcription.
Supporting Evidence:
PMID:15131783
Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin.
GO:2001234 negative regulation of apoptotic signaling pathway
IMP
PMID:20454446
WNT4/beta-catenin pathway maintains female germ cell surviva... 		KEEP AS NON CORE
Summary: Genetic evidence links beta-catenin to dampening apoptotic signaling, plausibly via Wnt survival-gene transcription; a downstream regulatory phenotype.
Reason: Downstream survival-signaling modulation via Wnt transcription.
Supporting Evidence:
PMID:20454446
WNT4/beta-catenin pathway maintains female germ cell survival by inhibiting activin betaB in the mouse fetal ovary.
GO:2001234 negative regulation of apoptotic signaling pathway
IGI
PMID:20454446
WNT4/beta-catenin pathway maintains female germ cell surviva... 		KEEP AS NON CORE
Summary: Genetic evidence links beta-catenin to dampening apoptotic signaling, plausibly via Wnt survival-gene transcription; a downstream regulatory phenotype.
Reason: Downstream survival-signaling modulation via Wnt transcription.
Supporting Evidence:
PMID:20454446
WNT4/beta-catenin pathway maintains female germ cell survival by inhibiting activin betaB in the mouse fetal ovary.
GO:0003676 nucleic acid binding
EXP
PMID:21075118
Biochemical and structural characterization of Ξ²-catenin int... 		MODIFY
Summary: Beta-catenin does not bind DNA sequence-specifically; its genuine nucleic-acid-associated role is chromatin association within TCF/LEF complexes.
Reason: Over-general/likely indirect; replace with chromatin binding which it genuinely does.
Proposed replacements: chromatin binding
Supporting Evidence:
PMID:21075118
Biochemical and structural characterization of Ξ²-catenin interactions with nonphosphorylated and CK2-phosphorylated Lef-1.
GO:0001221 transcription coregulator binding
IPI
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells a... 		KEEP AS NON CORE
Summary: Binding to transcription coregulators broadens beta-catenin's coactivator interactions; specific TF/coactivator terms more directly capture the core Wnt role.
Reason: Generic-ish nuclear MF; IPI, supportive.
Supporting Evidence:
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
GO:0045944 positive regulation of transcription by RNA polymerase II
IBA
GO_REF:0000033 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
GO:0005634 nucleus
IBA
GO_REF:0000033 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
GO:0098609 cell-cell adhesion
IBA
GO_REF:0000033 		ACCEPT
Summary: Beta-catenin is essential for cadherin-based cell-cell adhesion, anchoring the adhesion complex to the cytoskeleton.
Reason: Core adhesion process; IBA/IMP-supported.
GO:0045296 cadherin binding
IBA
GO_REF:0000033 		ACCEPT
Summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
Reason: Core structural MF; crystallographically defined, IPI/IBA.
Supporting Evidence:
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0060070 canonical Wnt signaling pathway
IBA
GO_REF:0000033 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0016922 nuclear receptor binding
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: Beta-catenin coactivates several nuclear receptors (e.g. NR5A2, AR/ER), broadening its transcriptional crosstalk beyond the core TCF/LEF axis.
Reason: Crosstalk coactivation; non-core relative to TCF.
GO:0005737 cytoplasm
IBA
GO_REF:0000033 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
GO:0019903 protein phosphatase binding
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: Protein-phosphatase binding (e.g. PTPN6/PTPRJ) regulates tyrosine-phosphorylation of junctional beta-catenin, a regulatory interaction.
Reason: Regulatory partner; IBA/IPI, non-core.
GO:0045294 alpha-catenin binding
IBA
GO_REF:0000033 		ACCEPT
Summary: Beta-catenin binds alpha-catenin via its N-terminal region, the key linkage coupling the cadherin-catenin complex to the actin cytoskeleton.
Reason: Core structural MF; crystallographically defined, IPI/IDA.
GO:0005912 adherens junction
IBA
GO_REF:0000033 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0016342 catenin complex
IBA
GO_REF:0000033 		ACCEPT
Summary: Beta-catenin is a defining member of the catenin (cadherin-catenin) complex linking cadherins to alpha-catenin/actin.
Reason: Core complex; broadly supported (IBA/IDA/IMP/ISS).
GO:0003713 transcription coactivator activity
IBA
GO_REF:0000033 		ACCEPT
Summary: The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.
Reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
Supporting Evidence:
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0000922 spindle pole
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: A mitotic spindle-pole pool (via NEK2) reflects a centrosome-related moonlighting localization, distinct from core adhesion/Wnt roles.
Reason: Secondary localization; IEA, non-core.
GO:0005634 nucleus
IEA
GO_REF:0000120 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
GO:0005737 cytoplasm
IEA
GO_REF:0000120 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
GO:0005813 centrosome
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Beta-catenin has a reported centrosomal pool acting in centrosome cohesion/separation, distinct from its core adhesion and Wnt roles.
Reason: Secondary localization; IDA but non-core moonlighting.
GO:0005856 cytoskeleton
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: Cytoskeleton localization reflects indirect cortical actin association via the cadherin-catenin complex; the specific junctional terms are more informative.
Reason: Over-general CC parent; electronic.
GO:0005886 plasma membrane
IEA
GO_REF:0000120 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
GO:0005912 adherens junction
IEA
GO_REF:0000120 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0007155 cell adhesion
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Generic cell adhesion is subsumed by the more specific cadherin-mediated cell-cell adhesion terms that capture beta-catenin's actual mechanism.
Reason: Over-general parent; electronic; specific child preferred.
GO:0007399 nervous system development
IEA
GO_REF:0000043 		MARK AS OVER ANNOTATED
Summary: Pure-IEA, system-wide nervous-system development is too high-level to be informative; beta-catenin's specific CNS roles are captured by finer child terms.
Reason: Vague IEA umbrella adding nothing over specific neural terms; over-annotation.
GO:0016020 membrane
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
Reason: Over-general CC parent.
GO:0016055 Wnt signaling pathway
IEA
GO_REF:0000043 		MODIFY
Summary: beta-catenin acts specifically in the CANONICAL (beta-catenin-dependent) Wnt branch, not the non-canonical branches. The generic parent should be specialized.
Reason: IEA generic parent; specific canonical child available and well supported.
Proposed replacements: canonical Wnt signaling pathway
GO:0045202 synapse
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: Synaptic localization supports cadherin-based synaptic adhesion in neurons, a tissue-specific pool.
Reason: Synapse localization; IDA/IEA, non-core.
GO:0045216 cell-cell junction organization
IEA
GO_REF:0000117 		ACCEPT
Summary: Beta-catenin contributes to organizing cell-cell junctions through assembly of the cadherin-catenin adhesion complex.
Reason: Core adhesion process; consistent with junction roles.
GO:0045296 cadherin binding
IEA
GO_REF:0000120 		ACCEPT
Summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
Reason: Core structural MF; crystallographically defined, IPI/IBA.
Supporting Evidence:
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0070161 anchoring junction
IEA
GO_REF:0000044 		ACCEPT
Summary: Beta-catenin localizes to anchoring junctions (adherens junctions), consistent with its cadherin-catenin structural role.
Reason: Core localization parent of adherens junction.
GO:0005515 protein binding
IPI
PMID:10481074
A GSK3-binding peptide from FRAT1 selectively inhibits the G... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:10481074
A GSK3-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed phosphorylation of axin and beta-catenin.
GO:0005515 protein binding
IPI
PMID:10873669
Identification of a novel beta-catenin-interacting protein. 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:10873669
Identification of a novel beta-catenin-interacting protein.
GO:0005515 protein binding
IPI
PMID:10882138
Structure of the dimerization and beta-catenin-binding regio... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:10882138
Structure of the dimerization and beta-catenin-binding region of alpha-catenin.
GO:0005515 protein binding
IPI
PMID:11348595
The structure of the beta-catenin/E-cadherin complex and the... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:11348595
The structure of the beta-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by beta-catenin.
GO:0005515 protein binding
IPI
PMID:12408825
ICAT inhibits beta-catenin binding to Tcf/Lef-family transcr... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:12408825
ICAT inhibits beta-catenin binding to Tcf/Lef-family transcription factors and the general coactivator p300 using independent structural modules.
GO:0005515 protein binding
IPI
PMID:12421363
Axin negatively affects tau phosphorylation by glycogen synt... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:12421363
Axin negatively affects tau phosphorylation by glycogen synthase kinase 3beta.
GO:0005515 protein binding
IPI
PMID:12874278
The PDZ protein tax-interacting protein-1 inhibits beta-cate... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:12874278
The PDZ protein tax-interacting protein-1 inhibits beta-catenin transcriptional activity and growth of colorectal cancer cells.
GO:0005515 protein binding
IPI
PMID:14691142
alpha3beta1 integrin-CD151, a component of the cadherin-cate... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:14691142
alpha3beta1 integrin-CD151, a component of the cadherin-catenin complex, regulates PTPmu expression and cell-cell adhesion.
GO:0005515 protein binding
IPI
PMID:15327768
Mechanism of phosphorylation-dependent binding of APC to bet... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:15327768
Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation.
GO:0005515 protein binding
IPI
PMID:16293619
Thermodynamics of beta-catenin-ligand interactions: the role... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:16293619
Thermodynamics of beta-catenin-ligand interactions: the roles of the N- and C-terminal tails in modulating binding affinity.
GO:0005515 protein binding
IPI
PMID:16678101
Homeodomain-mediated beta-catenin-dependent switching events... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:16678101
Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
GO:0005515 protein binding
IPI
PMID:19107203
Direct inhibition of GSK3beta by the phosphorylated cytoplas... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:19107203
Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling.
GO:0005515 protein binding
IPI
PMID:20531388
Mutant huntingtin-impaired degradation of beta-catenin cause... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:20531388
Mutant huntingtin-impaired degradation of beta-catenin causes neurotoxicity in Huntington's disease.
GO:0005515 protein binding
IPI
PMID:20837657
Abelson family kinases regulate Frizzled planar cell polarit... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:20837657
Abelson family kinases regulate Frizzled planar cell polarity signaling via Dsh phosphorylation.
GO:0005515 protein binding
IPI
PMID:21103407
The leukemia-associated Mllt10/Af10-Dot1l are Tcf4/Ξ²-catenin... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:21103407
The leukemia-associated Mllt10/Af10-Dot1l are Tcf4/Ξ²-catenin coactivators essential for intestinal homeostasis.
GO:0005515 protein binding
IPI
PMID:21552260
Nemo kinase phosphorylates Ξ²-catenin to promote ommatidial r... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:21552260
Nemo kinase phosphorylates Ξ²-catenin to promote ommatidial rotation and connects core PCP factors to E-cadherin-Ξ²-catenin.
GO:0005515 protein binding
IPI
PMID:21730140
Ezrin-mediated apical integrity is required for intestinal h... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:21730140
Ezrin-mediated apical integrity is required for intestinal homeostasis.
GO:0005515 protein binding
IPI
PMID:21751375
Functional analysis of novel phosphorylation sites of CREB-b... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:21751375
Functional analysis of novel phosphorylation sites of CREB-binding protein using mass spectrometry and mammalian two-hybrid assays.
GO:0005515 protein binding
IPI
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells a... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
GO:0005515 protein binding
IPI
PMID:23273993
Intestinal tumorigenesis initiated by dedifferentiation and ... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:23273993
Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties.
GO:0005515 protein binding
IPI
PMID:25873176
TGIF governs a feed-forward network that empowers Wnt signal... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:25873176
TGIF governs a feed-forward network that empowers Wnt signaling to drive mammary tumorigenesis.
GO:0005515 protein binding
IPI
PMID:26893351
The transcription factor SOX6 contributes to the development... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:26893351
The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis.
GO:0005515 protein binding
IPI
PMID:9264463
A specific domain in alpha-catenin mediates binding to beta-... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:9264463
A specific domain in alpha-catenin mediates binding to beta-catenin or plakoglobin.
GO:0000209 protein polyubiquitination
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: beta-catenin is the polyubiquitinated SUBSTRATE (K48 chains via SCF-BTRC), not the ligase; this IEA/ISO term reflects its targeting for degradation and is non-core.
Reason: Substrate (not catalytic) involvement; electronic, kept as non-core.
GO:0000791 euchromatin
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: beta-catenin localizes with active TCF/LEF target loci in euchromatin, consistent with its coactivator role, but this CC term is contextual rather than a core function statement.
Reason: Localization term supporting, but not equal to, its coactivator function.
GO:0001649 osteoblast differentiation
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Wnt/beta-catenin is a master driver of osteoblast fate via Runx2/Osterix-linked targets; the differentiation outcome is downstream of that transcription.
Reason: Osteoblastogenesis downstream of Wnt/beta-catenin transcriptional program.
GO:0003713 transcription coactivator activity
ISO
GO_REF:0000119 		ACCEPT
Summary: The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.
Reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
Supporting Evidence:
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005102 signaling receptor binding
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Reported signaling-receptor binding is a generic descriptor of regulatory contacts and not a core, mechanistically defined function.
Reason: Semi-generic MF; electronic, peripheral.
GO:0005634 nucleus
ISO
GO_REF:0000096 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
GO:0005634 nucleus
ISO
GO_REF:0000119 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
GO:0005667 transcription regulator complex
ISO
GO_REF:0000119 		ACCEPT
Summary: Beta-catenin is a component of transcription regulator complexes (with TCF/LEF and coactivators) that drive Wnt target gene expression.
Reason: Core nuclear Wnt effector complex; IDA-supported.
GO:0005737 cytoplasm
ISO
GO_REF:0000096 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
GO:0005737 cytoplasm
ISO
GO_REF:0000119 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
GO:0005813 centrosome
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Beta-catenin has a reported centrosomal pool acting in centrosome cohesion/separation, distinct from its core adhesion and Wnt roles.
Reason: Secondary localization; IDA but non-core moonlighting.
GO:0005829 cytosol
ISO
GO_REF:0000119 		ACCEPT
Summary: Beta-catenin has a cytosolic pool subject to destruction-complex regulation and Wnt-dependent stabilization.
Reason: Genuine pool; IDA/TAS-supported.
GO:0005886 plasma membrane
ISO
GO_REF:0000096 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
GO:0005886 plasma membrane
ISO
GO_REF:0000119 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
GO:0005911 cell-cell junction
ISO
GO_REF:0000119 		ACCEPT
Summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
Reason: Core junctional localization; IDA.
GO:0005912 adherens junction
ISO
GO_REF:0000096 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005912 adherens junction
ISO
GO_REF:0000119 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005929 cilium
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Beta-catenin is reported at the cilium where Wnt/cytoskeletal regulation occurs; an electronically inferred location (IEA/ISO) secondary to junction and nuclear pools.
Reason: electronic secondary localization, non-core
GO:0005938 cell cortex
ISO
GO_REF:0000119 		ACCEPT
Summary: Beta-catenin associates with the actin-rich cell cortex via the cadherin-catenin complex at cell-cell contacts.
Reason: Genuine cortical pool at junctions.
GO:0007155 cell adhesion
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Generic cell adhesion is subsumed by the more specific cadherin-mediated cell-cell adhesion terms that capture beta-catenin's actual mechanism.
Reason: Over-general parent; electronic; specific child preferred.
GO:0007173 epidermal growth factor receptor signaling pathway
ISO
GO_REF:0000119 		REMOVE
Summary: Beta-catenin is a Wnt-pathway effector and adherens-junction protein, not a component of EGFR signaling; this electronically propagated (IEA/ISO) term is biologically misattributed.
Reason: electronic; EGFR pathway not a beta-catenin role
GO:0008285 negative regulation of cell population proliferation
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Electronic/ortholog-inferred anti-proliferative effect in some lineages, downstream of context-specific Wnt transcriptional output.
Reason: Context anti-proliferation downstream of transcription; non-core (electronic).
GO:0010629 negative regulation of gene expression
ISO
GO_REF:0000096 		MARK AS OVER ANNOTATED
Summary: Generic negative-regulation-of-expression parent; beta-catenin's specific repressive effects act at the level of Pol II transcription of particular targets.
Reason: Uninformative broad parent; specific Pol II transcription terms preferred.
GO:0010717 regulation of epithelial to mesenchymal transition
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Generic EMT regulation reflects beta-catenin's dual junctional and Wnt-transcriptional control of epithelial plasticity; an electronic/ortholog-inferred downstream process.
Reason: Downstream EMT control via Wnt transcription and cadherin-adhesion balance; non-core.
GO:0010718 positive regulation of epithelial to mesenchymal transition
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Nuclear beta-catenin drives EMT transcriptional programs (Snail/Twist targets) while loss of its junctional pool also promotes EMT; the process is downstream of both core roles.
Reason: EMT is a transcriptional/adhesion downstream output, not beta-catenin's direct molecular function.
GO:0010909 positive regulation of heparan sulfate proteoglycan biosynthetic process
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Ortholog/electronic-inferred up-regulation of HSPG biosynthesis, plausibly via Wnt transcriptional targets; a downstream biosynthetic effect.
Reason: HSPG biosynthesis upregulation downstream of transcription; non-core (electronic).
GO:0014010 Schwann cell proliferation
ISO
GO_REF:0000096 		KEEP AS NON CORE
Summary: Beta-catenin supports Schwann cell proliferation via Wnt/TCF transcriptional output; a peripheral-glia proliferation outcome downstream of its signaling role, not a core molecular function.
Reason: ISO-supported downstream Wnt-driven glial proliferation phenotype
GO:0014704 intercalated disc
ISO
GO_REF:0000096 		ACCEPT
Summary: Beta-catenin is a core structural component of the cardiac intercalated disc, anchoring N-cadherin to the actin cytoskeleton (IDA/ISO); a direct adhesion-structure localization.
Reason: direct structural localization at cardiac junction
GO:0016020 membrane
ISO
GO_REF:0000096 		KEEP AS NON CORE
Summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
Reason: Over-general CC parent.
GO:0016323 basolateral plasma membrane
ISO
GO_REF:0000119 		ACCEPT
Summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
Reason: Genuine junctional pool; IDA-supported.
GO:0016324 apical plasma membrane
ISO
GO_REF:0000096 		KEEP AS NON CORE
Summary: Apical plasma membrane pool is a context-specific epithelial localization; beta-catenin junctions are chiefly apicolateral/lateral.
Reason: Secondary membrane subdomain; electronic (ISO).
GO:0016328 lateral plasma membrane
ISO
GO_REF:0000096 		ACCEPT
Summary: Beta-catenin concentrates at the lateral membrane of epithelia where cadherin-based cell-cell junctions assemble.
Reason: Genuine core junctional membrane pool; IDA.
GO:0016328 lateral plasma membrane
ISO
GO_REF:0000119 		ACCEPT
Summary: Beta-catenin concentrates at the lateral membrane of epithelia where cadherin-based cell-cell junctions assemble.
Reason: Genuine core junctional membrane pool; IDA.
GO:0016342 catenin complex
ISO
GO_REF:0000119 		ACCEPT
Summary: Beta-catenin is a defining member of the catenin (cadherin-catenin) complex linking cadherins to alpha-catenin/actin.
Reason: Core complex; broadly supported (IBA/IDA/IMP/ISS).
GO:0016922 nuclear receptor binding
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Beta-catenin coactivates several nuclear receptors (e.g. NR5A2, AR/ER), broadening its transcriptional crosstalk beyond the core TCF/LEF axis.
Reason: Crosstalk coactivation; non-core relative to TCF.
GO:0019899 enzyme binding
ISO
GO_REF:0000119 		MARK AS OVER ANNOTATED
Summary: Bare 'enzyme binding' is uninformative; beta-catenin's relevant enzyme contacts (GSK3B, CK1, kinases) are captured by specific kinase/phosphatase terms.
Reason: Generic MF over-annotation.
GO:0019900 kinase binding
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Generic kinase binding reflects contacts with regulatory kinases (GSK3B, CK1, CDKs); informative specificity is in destruction-complex and PTM annotations.
Reason: Semi-generic MF; electronic, peripheral.
GO:0019902 phosphatase binding
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Phosphatase binding (e.g. PTPRJ/PTPRU) regulates the phosphorylation state of junctional beta-catenin, a regulatory interaction.
Reason: Regulatory partner; electronic, non-core.
GO:0030054 cell junction
ISO
GO_REF:0000119 		ACCEPT
Summary: Beta-catenin is a core cell-junction protein, concentrated at cadherin-based cell-cell junctions.
Reason: Core localization (junction parent).
GO:0030331 nuclear estrogen receptor binding
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Estrogen-receptor binding represents nuclear-receptor coactivator crosstalk, secondary to TCF/LEF-based Wnt transcription.
Reason: Crosstalk partner; electronic, non-core.
GO:0030877 beta-catenin destruction complex
ISO
GO_REF:0000119 		ACCEPT
Summary: In the absence of Wnt, beta-catenin is the substrate within the AXIN/APC/GSK3B/CK1 destruction complex that drives its phosphorylation and degradation.
Reason: Core Wnt regulation; defining complex membership (IDA/ISS).
GO:0030997 regulation of centriole-centriole cohesion
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Beta-catenin has a reported centrosomal moonlighting role in centriole cohesion; ortholog/electronic-inferred and distinct from its core adhesion/Wnt roles.
Reason: Centrosomal moonlighting role, electronic-inferred; non-core.
GO:0031396 regulation of protein ubiquitination
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Reflects beta-catenin being targeted for / influencing ubiquitination within the destruction complex; an IEA/ISO regulatory term peripheral to its effector function.
Reason: Indirect/substrate-side ubiquitination regulation; electronic, non-core.
GO:0031625 ubiquitin protein ligase binding
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Binding E3 ligases (BTRC/SCF, SIAH1, UBR5) underlies beta-catenin's regulated turnover, a degradation-regulatory interaction.
Reason: Regulatory partner; ISO, non-core.
GO:0031965 nuclear membrane
ISO
GO_REF:0000096 		KEEP AS NON CORE
Summary: A nuclear-membrane pool may reflect nucleocytoplasmic shuttling, peripheral to the functional nuclear (chromatin/TCF) and junctional pools.
Reason: Secondary localization; ISO.
GO:0032355 response to estradiol
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Ortholog/electronic-inferred responsiveness to estradiol, reflecting hormone crosstalk with Wnt/beta-catenin transcription in reproductive tissues; a downstream response.
Reason: Estradiol response downstream/crosstalk with Wnt transcription; non-core (electronic).
GO:0032991 protein-containing complex
ISO
GO_REF:0000096 		MARK AS OVER ANNOTATED
Summary: Bare 'protein-containing complex' is uninformative; beta-catenin's specific complexes (catenin, TCF, destruction) are annotated separately.
Reason: Generic CC over-annotation.
GO:0032993 protein-DNA complex
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Beta-catenin is part of protein-DNA complexes only indirectly via TCF/LEF; the specific beta-catenin-TCF complex terms capture this better.
Reason: Indirect/over-general; electronic.
GO:0033234 negative regulation of protein sumoylation
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Ortholog/electronic-inferred negative effect on SUMOylation; an indirect downstream activity unrelated to beta-catenin's core adhesion/Wnt functions.
Reason: SUMOylation suppression, electronic-inferred and indirect; non-core.
GO:0034097 response to cytokine
ISO
GO_REF:0000096 		UNDECIDED
Summary: Sole ISO ortholog-transfer with no specific cytokine context; while crosstalk between beta-catenin and cytokine pathways exists, the bare term is too unspecific to confidently retain or refute.
Reason: ISO-only, no specific evidence; mark UNDECIDED rather than REMOVE per electronic-evidence caution.
GO:0034112 positive regulation of homotypic cell-cell adhesion
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Promotion of homotypic adhesion follows from beta-catenin's cadherin role, but the directional regulatory term is electronic and secondary to the structural terms.
Reason: Regulatory process; IEA/ISO.
GO:0034333 adherens junction assembly
ISO
GO_REF:0000119 		ACCEPT
Summary: By linking cadherin to the catenin/actin machinery, beta-catenin is required for adherens junction assembly.
Reason: Core adhesion process; mechanistically central even if evidence is electronic/ISS.
GO:0034394 protein localization to cell surface
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Beta-catenin promotes surface delivery/retention of cadherin (e.g. via vinculin), a supporting trafficking role secondary to its structural function.
Reason: Peripheral process; electronic.
GO:0035255 ionotropic glutamate receptor binding
ISO
GO_REF:0000096 		KEEP AS NON CORE
Summary: Reported binding to ionotropic glutamate receptors is a neuron-specific interaction tied to synaptic adhesion, not a core function.
Reason: Specific neuronal partner; ISO.
GO:0036064 ciliary basal body
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Beta-catenin has been localized to the ciliary basal body, linking junction/centrosome pools; an electronically inferred location (IEA/ISO) peripheral to its core roles.
Reason: electronic minor localization, non-core
GO:0043065 positive regulation of apoptotic process
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: In some contexts beta-catenin promotes apoptosis; this electronic/ortholog-inferred bidirectional effect is a downstream consequence of context-specific transcription.
Reason: Context-dependent pro-apoptotic output downstream of transcription; non-core (electronic).
GO:0043066 negative regulation of apoptotic process
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Beta-catenin Wnt targets (e.g. survival genes) can suppress apoptosis; this electronic/ortholog-inferred pro-survival effect is downstream of transcription.
Reason: Anti-apoptotic effect downstream of Wnt-target gene expression; non-core (electronic).
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
ISO
GO_REF:0000119 		ACCEPT
Summary: Core to beta-catenin level control: phosphorylated beta-catenin is the SUBSTRATE ubiquitinated by SCF(BTRC) and degraded by the proteasome, the switch that gates Wnt signaling.
Reason: Defining degradation process that regulates beta-catenin abundance.
Supporting Evidence:
file:mouse/Ctnnb1/Ctnnb1-deep-research-falcon.md
enabling recognition by **Ξ²-TrCP** (E3 ligase adaptor), ubiquitination, and proteasomal degradation
GO:0043198 dendritic shaft
ISO
GO_REF:0000096 		KEEP AS NON CORE
Summary: The dendritic-shaft pool is a neuron-specific localization tied to synaptic adhesion, secondary to core junction/Wnt pools.
Reason: Tissue-specific localization; ISO.
GO:0043525 positive regulation of neuron apoptotic process
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Ortholog-inferred pro-apoptotic effect on neurons in particular contexts, downstream of beta-catenin's transcriptional program.
Reason: Context-specific neuronal apoptosis downstream of Wnt transcription; non-core (electronic).
GO:0043627 response to estrogen
ISO
GO_REF:0000096 		KEEP AS NON CORE
Summary: ISO ortholog-inferred estrogen responsiveness, consistent with estrogen-Wnt crosstalk in hormone-responsive tissues; a downstream response phenotype.
Reason: Estrogen response via hormone-Wnt crosstalk; non-core (electronic).
GO:0044325 transmembrane transporter binding
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Binding to transmembrane transporters/channels (e.g. TRPV4, SLC30A9) reflects context-specific interactions peripheral to core functions.
Reason: Specific peripheral partner class; electronic.
GO:0044331 cell-cell adhesion mediated by cadherin
ISO
GO_REF:0000119 		ACCEPT
Summary: Beta-catenin mediates cadherin-dependent cell-cell adhesion, the precise process matching its molecular role.
Reason: Core, mechanistically specific adhesion term.
GO:0044877 protein-containing complex binding
ISO
GO_REF:0000096 		MARK AS OVER ANNOTATED
Summary: Generic 'complex binding' adds no functional specificity over the named complex-membership and partner-binding terms.
Reason: Generic MF over-annotation; ISO.
GO:0045294 alpha-catenin binding
ISO
GO_REF:0000096 		ACCEPT
Summary: Beta-catenin binds alpha-catenin via its N-terminal region, the key linkage coupling the cadherin-catenin complex to the actin cytoskeleton.
Reason: Core structural MF; crystallographically defined, IPI/IDA.
GO:0045294 alpha-catenin binding
ISO
GO_REF:0000119 		ACCEPT
Summary: Beta-catenin binds alpha-catenin via its N-terminal region, the key linkage coupling the cadherin-catenin complex to the actin cytoskeleton.
Reason: Core structural MF; crystallographically defined, IPI/IDA.
GO:0045296 cadherin binding
ISO
GO_REF:0000096 		ACCEPT
Summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
Reason: Core structural MF; crystallographically defined, IPI/IBA.
Supporting Evidence:
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0045296 cadherin binding
ISO
GO_REF:0000119 		ACCEPT
Summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
Reason: Core structural MF; crystallographically defined, IPI/IBA.
Supporting Evidence:
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0045892 negative regulation of DNA-templated transcription
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: beta-catenin can repress specific targets (e.g. via SOX9/TCF competition or unliganded-TCF contexts), but its core, defining transcriptional role is positive coactivation of TCF/LEF targets.
Reason: Context-dependent repression; secondary to its activating role.
GO:0045893 positive regulation of DNA-templated transcription
ISO
GO_REF:0000119 		MODIFY
Summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
Reason: Generic parent; specialize to Pol II-specific positive regulation.
GO:0045944 positive regulation of transcription by RNA polymerase II
ISO
GO_REF:0000119 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
GO:0046332 SMAD binding
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: SMAD binding represents BMP/TGF-beta pathway crosstalk, secondary to beta-catenin's cadherin-adhesion and Wnt/TCF core functions.
Reason: Crosstalk; electronic (IEA/ISO) and not a core partner class.
GO:0048471 perinuclear region of cytoplasm
ISO
GO_REF:0000096 		KEEP AS NON CORE
Summary: A perinuclear cytoplasmic pool may reflect shuttling/staging intermediates, secondary to functional junctional and nuclear pools.
Reason: Secondary localization; electronic.
GO:0048471 perinuclear region of cytoplasm
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: A perinuclear cytoplasmic pool may reflect shuttling/staging intermediates, secondary to functional junctional and nuclear pools.
Reason: Secondary localization; electronic.
GO:0048660 regulation of smooth muscle cell proliferation
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Modulation of vascular/visceral smooth muscle proliferation reflects Wnt/beta-catenin mitogenic target genes; ortholog/electronic-inferred downstream process.
Reason: Downstream proliferative control via Wnt transcriptional targets; non-core.
GO:0050998 nitric-oxide synthase binding
ISO
GO_REF:0000096 		KEEP AS NON CORE
Summary: eNOS-associated binding relates to S-nitrosylation-regulated junction disassembly in endothelium, a regulatory crosstalk interaction.
Reason: Specific partner; ISO, peripheral.
GO:0060070 canonical Wnt signaling pathway
ISO
GO_REF:0000119 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0060231 mesenchymal to epithelial transition
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Beta-catenin contributes to MET through cadherin-junction assembly and Wnt transcriptional balance; a cell-state transition (electronic) downstream of its dual role.
Reason: electronic; downstream of junction/Wnt MET role
GO:0061154 endothelial tube morphogenesis
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Beta-catenin supports endothelial tube formation via junctional integrity and Wnt transcription; a vascular morphogenetic outcome (electronic) downstream of its dual role.
Reason: electronic; downstream of junction/Wnt vascular roles
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
ISO
GO_REF:0000119 		ACCEPT
Summary: Beta-catenin directly binds Pol II-specific DNA-binding transcription factors (TCF/LEF) to drive Wnt-responsive transcription.
Reason: Core Wnt coactivation; IDA-supported specific TF binding.
GO:0070097 delta-catenin binding
ISO
GO_REF:0000096 		KEEP AS NON CORE
Summary: Binding to delta-catenin (CTNND2) occurs in neuronal contexts; p120/delta-catenin family members bind the cadherin juxtamembrane region, a secondary interaction for beta-catenin.
Reason: Specific partner binding; ISO and peripheral.
GO:0070160 tight junction
ISO
GO_REF:0000096 		ACCEPT
Summary: Beta-catenin localizes to the tight-junction-associated region of the epithelial apical junctional complex via cadherin-catenin contacts.
Reason: Junctional localization within apical complex; retain (ISO).
GO:0070369 beta-catenin-TCF7L2 complex
ISO
GO_REF:0000119 		ACCEPT
Summary: Beta-catenin forms the specific transcriptional complex with TCF7L2/TCF4 that activates Wnt target genes.
Reason: Core Wnt effector complex (specific TCF member).
GO:0070411 I-SMAD binding
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Inhibitory-SMAD binding reflects TGF-beta/BMP crosstalk rather than the canonical cadherin or Wnt/TCF functions of beta-catenin.
Reason: Crosstalk binding; electronic (IEA/ISO) and peripheral to core roles.
GO:0070602 regulation of centromeric sister chromatid cohesion
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: A reported beta-catenin role at centromeric cohesion is a moonlighting function separate from its Wnt/adhesion core; supported by IMP plus electronic inference.
Reason: Sister-chromatid cohesion moonlighting role; non-core to Wnt/adhesion.
GO:0071260 cellular response to mechanical stimulus
ISO
GO_REF:0000096 		KEEP AS NON CORE
Summary: Mechanical force at adherens junctions modulates beta-catenin release/signaling (mechanotransduction); a context response (ISO) downstream of its junctional role.
Reason: ISO mechanotransduction downstream of junction role
GO:0071363 cellular response to growth factor stimulus
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Beta-catenin participates in growth-factor-responsive transcription via Wnt crosstalk; a broad, electronically inferred response, kept as non-core given indirect linkage.
Reason: electronic/generic; indirect crosstalk, not core
GO:0071681 cellular response to indole-3-methanol
ISO
GO_REF:0000119 		REMOVE
Summary: No credible biological basis for beta-catenin as a responder to indole-3-methanol; an electronically propagated (IEA/ISO/ISS) annotation with no support.
Reason: electronic annotation biologically unsupported for this gene
GO:0071944 cell periphery
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Beta-catenin localizes to the cell periphery at adherens junctions linking cadherins to actin; a broad location term consistent with its structural role but less specific than the junction terms.
Reason: electronic broad location subsumed by adherens-junction terms
GO:0072497 mesenchymal stem cell differentiation
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Beta-catenin directs MSC lineage choice (osteo/chondro/adipo) via Wnt/TCF transcription; a stem-cell fate outcome downstream of signaling.
Reason: downstream Wnt-driven MSC differentiation
GO:0090279 regulation of calcium ion import
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Ortholog/electronic-inferred influence on calcium import, distinct from beta-catenin's core Wnt/adhesion roles; a downstream/indirect effect.
Reason: Calcium-import regulation, electronic-inferred and indirect; non-core.
GO:0098609 cell-cell adhesion
ISO
GO_REF:0000096 		ACCEPT
Summary: Beta-catenin is essential for cadherin-based cell-cell adhesion, anchoring the adhesion complex to the cytoskeleton.
Reason: Core adhesion process; IBA/IMP-supported.
GO:0140297 DNA-binding transcription factor binding
ISO
GO_REF:0000119 		ACCEPT
Summary: Beta-catenin binds TCF/LEF DNA-binding transcription factors to coactivate Wnt target genes; core to its nuclear Wnt-effector role.
Reason: Core Wnt: direct TCF/LEF coactivation (IPI); foundational MF for the transcriptional arm.
GO:1905555 positive regulation of blood vessel branching
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling promotes endothelial branching morphogenesis via target-gene expression; ortholog-inferred downstream vascular process.
Reason: Vessel branching is downstream of Wnt/beta-catenin endothelial transcription.
GO:1990138 neuron projection extension
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Ortholog/electronic-inferred role in axon/dendrite outgrowth, plausibly via cadherin-junction and Wnt-transcriptional inputs; a downstream neuronal phenotype.
Reason: Neurite extension downstream of adhesion/Wnt roles; non-core (electronic).
GO:1990314 cellular response to insulin-like growth factor stimulus
ISO
GO_REF:0000096 		KEEP AS NON CORE
Summary: Beta-catenin can be engaged in IGF-responsive transcriptional output via signaling crosstalk; an indirect response (ISO) kept as non-core, not a core IGF-pathway role.
Reason: ISO indirect IGF crosstalk, not core function
GO:1990907 beta-catenin-TCF complex
ISO
GO_REF:0000119 		ACCEPT
Summary: The nuclear beta-catenin-TCF complex is the central transcriptional effector unit of canonical Wnt signaling.
Reason: Core Wnt effector complex; IDA-supported.
GO:2000008 regulation of protein localization to cell surface
ISO
GO_REF:0000119 		KEEP AS NON CORE
Summary: Beta-catenin modulates cadherin surface levels, a regulatory trafficking role secondary to its structural junction function.
Reason: Peripheral regulatory process; electronic.
GO:0000209 protein polyubiquitination
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: beta-catenin is the polyubiquitinated SUBSTRATE (K48 chains via SCF-BTRC), not the ligase; this IEA/ISO term reflects its targeting for degradation and is non-core.
Reason: Substrate (not catalytic) involvement; electronic, kept as non-core.
GO:0000791 euchromatin
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: beta-catenin localizes with active TCF/LEF target loci in euchromatin, consistent with its coactivator role, but this CC term is contextual rather than a core function statement.
Reason: Localization term supporting, but not equal to, its coactivator function.
GO:0001649 osteoblast differentiation
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Wnt/beta-catenin is a master driver of osteoblast fate via Runx2/Osterix-linked targets; the differentiation outcome is downstream of that transcription.
Reason: Osteoblastogenesis downstream of Wnt/beta-catenin transcriptional program.
GO:0003713 transcription coactivator activity
IEA
GO_REF:0000107 		ACCEPT
Summary: The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.
Reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
Supporting Evidence:
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005102 signaling receptor binding
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Reported signaling-receptor binding is a generic descriptor of regulatory contacts and not a core, mechanistically defined function.
Reason: Semi-generic MF; electronic, peripheral.
GO:0005667 transcription regulator complex
IEA
GO_REF:0000107 		ACCEPT
Summary: Beta-catenin is a component of transcription regulator complexes (with TCF/LEF and coactivators) that drive Wnt target gene expression.
Reason: Core nuclear Wnt effector complex; IDA-supported.
GO:0005829 cytosol
IEA
GO_REF:0000107 		ACCEPT
Summary: Beta-catenin has a cytosolic pool subject to destruction-complex regulation and Wnt-dependent stabilization.
Reason: Genuine pool; IDA/TAS-supported.
GO:0005911 cell-cell junction
IEA
GO_REF:0000107 		ACCEPT
Summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
Reason: Core junctional localization; IDA.
GO:0005929 cilium
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Beta-catenin is reported at the cilium where Wnt/cytoskeletal regulation occurs; an electronically inferred location (IEA/ISO) secondary to junction and nuclear pools.
Reason: electronic secondary localization, non-core
GO:0005938 cell cortex
IEA
GO_REF:0000107 		ACCEPT
Summary: Beta-catenin associates with the actin-rich cell cortex via the cadherin-catenin complex at cell-cell contacts.
Reason: Genuine cortical pool at junctions.
GO:0007173 epidermal growth factor receptor signaling pathway
IEA
GO_REF:0000107 		REMOVE
Summary: Beta-catenin is a Wnt-pathway effector and adherens-junction protein, not a component of EGFR signaling; this electronically propagated (IEA/ISO) term is biologically misattributed.
Reason: electronic; EGFR pathway not a beta-catenin role
GO:0008285 negative regulation of cell population proliferation
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Electronic/ortholog-inferred anti-proliferative effect in some lineages, downstream of context-specific Wnt transcriptional output.
Reason: Context anti-proliferation downstream of transcription; non-core (electronic).
GO:0009410 response to xenobiotic stimulus
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: IEA-inferred xenobiotic responsiveness; an indirect downstream response not central to beta-catenin's adhesion or Wnt-transcriptional function.
Reason: Xenobiotic response, IEA-inferred and indirect; non-core.
Supporting Evidence:
file:mouse/Ctnnb1/Ctnnb1-deep-research-falcon.md
enabling recognition by **Ξ²-TrCP** (E3 ligase adaptor), ubiquitination, and proteasomal degradation
GO:0010717 regulation of epithelial to mesenchymal transition
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Generic EMT regulation reflects beta-catenin's dual junctional and Wnt-transcriptional control of epithelial plasticity; an electronic/ortholog-inferred downstream process.
Reason: Downstream EMT control via Wnt transcription and cadherin-adhesion balance; non-core.
GO:0010718 positive regulation of epithelial to mesenchymal transition
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Nuclear beta-catenin drives EMT transcriptional programs (Snail/Twist targets) while loss of its junctional pool also promotes EMT; the process is downstream of both core roles.
Reason: EMT is a transcriptional/adhesion downstream output, not beta-catenin's direct molecular function.
GO:0010909 positive regulation of heparan sulfate proteoglycan biosynthetic process
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Ortholog/electronic-inferred up-regulation of HSPG biosynthesis, plausibly via Wnt transcriptional targets; a downstream biosynthetic effect.
Reason: HSPG biosynthesis upregulation downstream of transcription; non-core (electronic).
GO:0016323 basolateral plasma membrane
IEA
GO_REF:0000107 		ACCEPT
Summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
Reason: Genuine junctional pool; IDA-supported.
GO:0016328 lateral plasma membrane
IEA
GO_REF:0000107 		ACCEPT
Summary: Beta-catenin concentrates at the lateral membrane of epithelia where cadherin-based cell-cell junctions assemble.
Reason: Genuine core junctional membrane pool; IDA.
GO:0016342 catenin complex
IEA
GO_REF:0000107 		ACCEPT
Summary: Beta-catenin is a defining member of the catenin (cadherin-catenin) complex linking cadherins to alpha-catenin/actin.
Reason: Core complex; broadly supported (IBA/IDA/IMP/ISS).
GO:0016922 nuclear receptor binding
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Beta-catenin coactivates several nuclear receptors (e.g. NR5A2, AR/ER), broadening its transcriptional crosstalk beyond the core TCF/LEF axis.
Reason: Crosstalk coactivation; non-core relative to TCF.
GO:0019899 enzyme binding
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: Bare 'enzyme binding' is uninformative; beta-catenin's relevant enzyme contacts (GSK3B, CK1, kinases) are captured by specific kinase/phosphatase terms.
Reason: Generic MF over-annotation.
GO:0019900 kinase binding
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Generic kinase binding reflects contacts with regulatory kinases (GSK3B, CK1, CDKs); informative specificity is in destruction-complex and PTM annotations.
Reason: Semi-generic MF; electronic, peripheral.
GO:0019902 phosphatase binding
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Phosphatase binding (e.g. PTPRJ/PTPRU) regulates the phosphorylation state of junctional beta-catenin, a regulatory interaction.
Reason: Regulatory partner; electronic, non-core.
GO:0030054 cell junction
IEA
GO_REF:0000107 		ACCEPT
Summary: Beta-catenin is a core cell-junction protein, concentrated at cadherin-based cell-cell junctions.
Reason: Core localization (junction parent).
GO:0030331 nuclear estrogen receptor binding
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Estrogen-receptor binding represents nuclear-receptor coactivator crosstalk, secondary to TCF/LEF-based Wnt transcription.
Reason: Crosstalk partner; electronic, non-core.
GO:0030877 beta-catenin destruction complex
IEA
GO_REF:0000107 		ACCEPT
Summary: In the absence of Wnt, beta-catenin is the substrate within the AXIN/APC/GSK3B/CK1 destruction complex that drives its phosphorylation and degradation.
Reason: Core Wnt regulation; defining complex membership (IDA/ISS).
GO:0030997 regulation of centriole-centriole cohesion
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Beta-catenin has a reported centrosomal moonlighting role in centriole cohesion; ortholog/electronic-inferred and distinct from its core adhesion/Wnt roles.
Reason: Centrosomal moonlighting role, electronic-inferred; non-core.
GO:0031396 regulation of protein ubiquitination
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Reflects beta-catenin being targeted for / influencing ubiquitination within the destruction complex; an IEA/ISO regulatory term peripheral to its effector function.
Reason: Indirect/substrate-side ubiquitination regulation; electronic, non-core.
GO:0032355 response to estradiol
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Ortholog/electronic-inferred responsiveness to estradiol, reflecting hormone crosstalk with Wnt/beta-catenin transcription in reproductive tissues; a downstream response.
Reason: Estradiol response downstream/crosstalk with Wnt transcription; non-core (electronic).
GO:0032991 protein-containing complex
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: Bare 'protein-containing complex' is uninformative; beta-catenin's specific complexes (catenin, TCF, destruction) are annotated separately.
Reason: Generic CC over-annotation.
GO:0032993 protein-DNA complex
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Beta-catenin is part of protein-DNA complexes only indirectly via TCF/LEF; the specific beta-catenin-TCF complex terms capture this better.
Reason: Indirect/over-general; electronic.
GO:0033234 negative regulation of protein sumoylation
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Ortholog/electronic-inferred negative effect on SUMOylation; an indirect downstream activity unrelated to beta-catenin's core adhesion/Wnt functions.
Reason: SUMOylation suppression, electronic-inferred and indirect; non-core.
GO:0034112 positive regulation of homotypic cell-cell adhesion
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Promotion of homotypic adhesion follows from beta-catenin's cadherin role, but the directional regulatory term is electronic and secondary to the structural terms.
Reason: Regulatory process; IEA/ISO.
GO:0034333 adherens junction assembly
IEA
GO_REF:0000107 		ACCEPT
Summary: By linking cadherin to the catenin/actin machinery, beta-catenin is required for adherens junction assembly.
Reason: Core adhesion process; mechanistically central even if evidence is electronic/ISS.
GO:0034394 protein localization to cell surface
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Beta-catenin promotes surface delivery/retention of cadherin (e.g. via vinculin), a supporting trafficking role secondary to its structural function.
Reason: Peripheral process; electronic.
GO:0036064 ciliary basal body
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Beta-catenin has been localized to the ciliary basal body, linking junction/centrosome pools; an electronically inferred location (IEA/ISO) peripheral to its core roles.
Reason: electronic minor localization, non-core
GO:0043065 positive regulation of apoptotic process
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: In some contexts beta-catenin promotes apoptosis; this electronic/ortholog-inferred bidirectional effect is a downstream consequence of context-specific transcription.
Reason: Context-dependent pro-apoptotic output downstream of transcription; non-core (electronic).
GO:0043066 negative regulation of apoptotic process
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Beta-catenin Wnt targets (e.g. survival genes) can suppress apoptosis; this electronic/ortholog-inferred pro-survival effect is downstream of transcription.
Reason: Anti-apoptotic effect downstream of Wnt-target gene expression; non-core (electronic).
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IEA
GO_REF:0000107 		ACCEPT
Summary: Core to beta-catenin level control: phosphorylated beta-catenin is the SUBSTRATE ubiquitinated by SCF(BTRC) and degraded by the proteasome, the switch that gates Wnt signaling.
Reason: Defining degradation process that regulates beta-catenin abundance.
Supporting Evidence:
file:mouse/Ctnnb1/Ctnnb1-deep-research-falcon.md
enabling recognition by **Ξ²-TrCP** (E3 ligase adaptor), ubiquitination, and proteasomal degradation
GO:0043525 positive regulation of neuron apoptotic process
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Ortholog-inferred pro-apoptotic effect on neurons in particular contexts, downstream of beta-catenin's transcriptional program.
Reason: Context-specific neuronal apoptosis downstream of Wnt transcription; non-core (electronic).
GO:0044325 transmembrane transporter binding
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Binding to transmembrane transporters/channels (e.g. TRPV4, SLC30A9) reflects context-specific interactions peripheral to core functions.
Reason: Specific peripheral partner class; electronic.
GO:0044331 cell-cell adhesion mediated by cadherin
IEA
GO_REF:0000107 		ACCEPT
Summary: Beta-catenin mediates cadherin-dependent cell-cell adhesion, the precise process matching its molecular role.
Reason: Core, mechanistically specific adhesion term.
GO:0045294 alpha-catenin binding
IEA
GO_REF:0000120 		ACCEPT
Summary: Beta-catenin binds alpha-catenin via its N-terminal region, the key linkage coupling the cadherin-catenin complex to the actin cytoskeleton.
Reason: Core structural MF; crystallographically defined, IPI/IDA.
GO:0045892 negative regulation of DNA-templated transcription
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: beta-catenin can repress specific targets (e.g. via SOX9/TCF competition or unliganded-TCF contexts), but its core, defining transcriptional role is positive coactivation of TCF/LEF targets.
Reason: Context-dependent repression; secondary to its activating role.
GO:0045893 positive regulation of DNA-templated transcription
IEA
GO_REF:0000107 		MODIFY
Summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
Reason: Generic parent; specialize to Pol II-specific positive regulation.
GO:0045944 positive regulation of transcription by RNA polymerase II
IEA
GO_REF:0000107 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
GO:0046332 SMAD binding
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: SMAD binding represents BMP/TGF-beta pathway crosstalk, secondary to beta-catenin's cadherin-adhesion and Wnt/TCF core functions.
Reason: Crosstalk; electronic (IEA/ISO) and not a core partner class.
GO:0048471 perinuclear region of cytoplasm
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: A perinuclear cytoplasmic pool may reflect shuttling/staging intermediates, secondary to functional junctional and nuclear pools.
Reason: Secondary localization; electronic.
GO:0048660 regulation of smooth muscle cell proliferation
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Modulation of vascular/visceral smooth muscle proliferation reflects Wnt/beta-catenin mitogenic target genes; ortholog/electronic-inferred downstream process.
Reason: Downstream proliferative control via Wnt transcriptional targets; non-core.
GO:0060070 canonical Wnt signaling pathway
IEA
GO_REF:0000107 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0060231 mesenchymal to epithelial transition
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Beta-catenin contributes to MET through cadherin-junction assembly and Wnt transcriptional balance; a cell-state transition (electronic) downstream of its dual role.
Reason: electronic; downstream of junction/Wnt MET role
GO:0061154 endothelial tube morphogenesis
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Beta-catenin supports endothelial tube formation via junctional integrity and Wnt transcription; a vascular morphogenetic outcome (electronic) downstream of its dual role.
Reason: electronic; downstream of junction/Wnt vascular roles
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
IEA
GO_REF:0000107 		ACCEPT
Summary: Beta-catenin directly binds Pol II-specific DNA-binding transcription factors (TCF/LEF) to drive Wnt-responsive transcription.
Reason: Core Wnt coactivation; IDA-supported specific TF binding.
GO:0070369 beta-catenin-TCF7L2 complex
IEA
GO_REF:0000107 		ACCEPT
Summary: Beta-catenin forms the specific transcriptional complex with TCF7L2/TCF4 that activates Wnt target genes.
Reason: Core Wnt effector complex (specific TCF member).
GO:0070411 I-SMAD binding
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Inhibitory-SMAD binding reflects TGF-beta/BMP crosstalk rather than the canonical cadherin or Wnt/TCF functions of beta-catenin.
Reason: Crosstalk binding; electronic (IEA/ISO) and peripheral to core roles.
GO:0070602 regulation of centromeric sister chromatid cohesion
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: A reported beta-catenin role at centromeric cohesion is a moonlighting function separate from its Wnt/adhesion core; supported by IMP plus electronic inference.
Reason: Sister-chromatid cohesion moonlighting role; non-core to Wnt/adhesion.
GO:0071363 cellular response to growth factor stimulus
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Beta-catenin participates in growth-factor-responsive transcription via Wnt crosstalk; a broad, electronically inferred response, kept as non-core given indirect linkage.
Reason: electronic/generic; indirect crosstalk, not core
GO:0071681 cellular response to indole-3-methanol
IEA
GO_REF:0000107 		REMOVE
Summary: No credible biological basis for beta-catenin as a responder to indole-3-methanol; an electronically propagated (IEA/ISO/ISS) annotation with no support.
Reason: electronic annotation biologically unsupported for this gene
GO:0071944 cell periphery
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Beta-catenin localizes to the cell periphery at adherens junctions linking cadherins to actin; a broad location term consistent with its structural role but less specific than the junction terms.
Reason: electronic broad location subsumed by adherens-junction terms
GO:0072497 mesenchymal stem cell differentiation
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Beta-catenin directs MSC lineage choice (osteo/chondro/adipo) via Wnt/TCF transcription; a stem-cell fate outcome downstream of signaling.
Reason: downstream Wnt-driven MSC differentiation
GO:0090279 regulation of calcium ion import
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Ortholog/electronic-inferred influence on calcium import, distinct from beta-catenin's core Wnt/adhesion roles; a downstream/indirect effect.
Reason: Calcium-import regulation, electronic-inferred and indirect; non-core.
GO:0140297 DNA-binding transcription factor binding
IEA
GO_REF:0000107 		ACCEPT
Summary: Beta-catenin binds TCF/LEF DNA-binding transcription factors to coactivate Wnt target genes; core to its nuclear Wnt-effector role.
Reason: Core Wnt: direct TCF/LEF coactivation (IPI); foundational MF for the transcriptional arm.
GO:1905555 positive regulation of blood vessel branching
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling promotes endothelial branching morphogenesis via target-gene expression; ortholog-inferred downstream vascular process.
Reason: Vessel branching is downstream of Wnt/beta-catenin endothelial transcription.
GO:1990138 neuron projection extension
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Ortholog/electronic-inferred role in axon/dendrite outgrowth, plausibly via cadherin-junction and Wnt-transcriptional inputs; a downstream neuronal phenotype.
Reason: Neurite extension downstream of adhesion/Wnt roles; non-core (electronic).
GO:1990907 beta-catenin-TCF complex
IEA
GO_REF:0000107 		ACCEPT
Summary: The nuclear beta-catenin-TCF complex is the central transcriptional effector unit of canonical Wnt signaling.
Reason: Core Wnt effector complex; IDA-supported.
GO:2000008 regulation of protein localization to cell surface
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Beta-catenin modulates cadherin surface levels, a regulatory trafficking role secondary to its structural junction function.
Reason: Peripheral regulatory process; electronic.
GO:0060070 canonical Wnt signaling pathway
IDA
PMID:12408825
ICAT inhibits beta-catenin binding to Tcf/Lef-family transcr... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:12408825
ICAT inhibits beta-catenin binding to Tcf/Lef-family transcription factors and the general coactivator p300 using independent structural modules.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0000122 negative regulation of transcription by RNA polymerase II
IDA
PMID:10898789
Inhibition of Wnt signaling by ICAT, a novel beta-catenin-in... 		KEEP AS NON CORE
Summary: An IDA call; beta-catenin represses certain Pol II targets in specific contexts, but this should be downgraded relative to its core activating coactivator role, not removed.
Reason: Experimental (IDA); downgrade context-specific repression, do not REMOVE.
Supporting Evidence:
PMID:10898789
ICAT repressed the activity of the reporter gene in both cell lines in a dose-dependent manner
GO:0005634 nucleus
IDA
PMID:16936075
The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 exp... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:16936075
The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 expression during somitogenesis.
GO:0045597 positive regulation of cell differentiation
NAS
PMID:24847765
From inception to output, Tcf1 and Lef1 safeguard developmen... 		KEEP AS NON CORE
Summary: NAS-supported broad pro-differentiation role reflecting beta-catenin Wnt-driven fate gene activation; a downstream, non-specific process.
Reason: Umbrella pro-differentiation downstream of Wnt transcription (NAS).
Supporting Evidence:
PMID:24847765
From inception to output, Tcf1 and Lef1 safeguard development of T cells and innate immune cells.
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:16936075
The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 exp... 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
Supporting Evidence:
PMID:16936075
The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 expression during somitogenesis.
GO:0050767 regulation of neurogenesis
NAS
PMID:23377854
Physiological role of Ξ²-catenin/TCF signaling in neurons of ... 		KEEP AS NON CORE
Summary: NAS-supported broad neurogenesis regulation reflecting beta-catenin's Wnt control of neural progenitor fate/proliferation; a downstream umbrella process.
Reason: Umbrella neurogenesis regulation downstream of Wnt transcription (NAS).
Supporting Evidence:
PMID:23377854
Physiological role of Ξ²-catenin/TCF signaling in neurons of the adult brain.
GO:0060070 canonical Wnt signaling pathway
IDA
PMID:16936075
The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 exp... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:16936075
The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 expression during somitogenesis.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0090090 negative regulation of canonical Wnt signaling pathway
IDA
PMID:10898789
Inhibition of Wnt signaling by ICAT, a novel beta-catenin-in... 		KEEP AS NON CORE
Summary: IDA-supported feedback/auto-regulatory role (e.g. via SOX9-mediated degradation, Axin2 induction); real but a regulatory facet rather than the core effector function.
Reason: Feedback regulation of its own pathway; non-core regulatory facet.
Supporting Evidence:
PMID:10898789
Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein.
GO:0090575 RNA polymerase II transcription regulator complex
IPI
PMID:21075118
Biochemical and structural characterization of Ξ²-catenin int... 		ACCEPT
Summary: As a TCF/LEF coactivator beta-catenin is a component of Pol II transcription regulator complexes on Wnt target promoters.
Reason: Core nuclear Wnt effector; IPI-supported complex membership.
Supporting Evidence:
PMID:21075118
Biochemical and structural characterization of Ξ²-catenin interactions with nonphosphorylated and CK2-phosphorylated Lef-1.
GO:1990711 beta-catenin-ICAT complex
IPI
PMID:10898789
Inhibition of Wnt signaling by ICAT, a novel beta-catenin-in... 		KEEP AS NON CORE
Summary: ICAT (CTNNBIP1) binding sequesters beta-catenin from TCF/p300, an inhibitory complex regulating signaling rather than a core effector assembly.
Reason: Inhibitory regulatory complex; IPI but peripheral.
Supporting Evidence:
PMID:10898789
Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein.
GO:0005912 adherens junction
IDA
PMID:12494996
Loss of desmoglein 2 suggests essential functions for early ... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:12494996
Loss of desmoglein 2 suggests essential functions for early embryonic development and proliferation of embryonal stem cells.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0010717 regulation of epithelial to mesenchymal transition
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Generic EMT regulation reflects beta-catenin's dual junctional and Wnt-transcriptional control of epithelial plasticity; an electronic/ortholog-inferred downstream process.
Reason: Downstream EMT control via Wnt transcription and cadherin-adhesion balance; non-core.
GO:0060231 mesenchymal to epithelial transition
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Beta-catenin contributes to MET through cadherin-junction assembly and Wnt transcriptional balance; a cell-state transition (electronic) downstream of its dual role.
Reason: electronic; downstream of junction/Wnt MET role
GO:0003713 transcription coactivator activity
IDA
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells a... 		ACCEPT
Summary: The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.
Reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
Supporting Evidence:
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0045944 positive regulation of transcription by RNA polymerase II
IMP
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells a... 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
Supporting Evidence:
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
GO:1990226 histone methyltransferase binding
IPI
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells a... 		KEEP AS NON CORE
Summary: Beta-catenin can recruit chromatin-modifying machinery (e.g. SET/MLL methyltransferases) to Wnt targets, a coactivator-associated but specialized interaction.
Reason: Specific partner binding; IPI, peripheral.
Supporting Evidence:
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
GO:0005737 cytoplasm
IDA
PMID:27375112
Antagonistic Regulation of Intercellular Cohesion by Plakoph... 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:27375112
Antagonistic Regulation of Intercellular Cohesion by Plakophilins 1 and 3.
GO:0005912 adherens junction
IDA
PMID:27375112
Antagonistic Regulation of Intercellular Cohesion by Plakoph... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:27375112
Antagonistic Regulation of Intercellular Cohesion by Plakophilins 1 and 3.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005634 nucleus
IDA
PMID:27015268
Plakophilin-1, a Novel Wnt Signaling Regulator, Is Critical ... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:27015268
Plakophilin-1, a Novel Wnt Signaling Regulator, Is Critical for Tooth Development and Ameloblast Differentiation.
GO:0005737 cytoplasm
IDA
PMID:27015268
Plakophilin-1, a Novel Wnt Signaling Regulator, Is Critical ... 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:27015268
Plakophilin-1, a Novel Wnt Signaling Regulator, Is Critical for Tooth Development and Ameloblast Differentiation.
GO:0005886 plasma membrane
IDA
PMID:27015268
Plakophilin-1, a Novel Wnt Signaling Regulator, Is Critical ... 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
Supporting Evidence:
PMID:27015268
Plakophilin-1, a Novel Wnt Signaling Regulator, Is Critical for Tooth Development and Ameloblast Differentiation.
GO:0042734 presynaptic membrane
IDA
PMID:8909549
The catenin/cadherin adhesion system is localized in synapti... 		KEEP AS NON CORE
Summary: A presynaptic-membrane pool reflects synaptic cadherin adhesion, secondary to core junctional localization.
Reason: Synapse-specific; IDA, non-core.
Supporting Evidence:
PMID:8909549
The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones.
GO:0045211 postsynaptic membrane
IDA
PMID:8909549
The catenin/cadherin adhesion system is localized in synapti... 		KEEP AS NON CORE
Summary: A postsynaptic-membrane pool supports synaptic cadherin adhesion in neurons, a tissue-specific localization.
Reason: Synapse-specific; IDA, non-core.
Supporting Evidence:
PMID:8909549
The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones.
GO:0051963 regulation of synapse assembly
IMP
PMID:28641114
A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Comp... 		KEEP AS NON CORE
Summary: Beta-catenin regulates synapse assembly via cadherin adhesion in neurons, a tissue-specific role distinct from core epithelial functions.
Reason: Neuronal process; IDA/IMP, non-core.
Supporting Evidence:
PMID:28641114
A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Complexes in Stabilizing Spines and Functional Synapses in the Neocortex.
GO:0051963 regulation of synapse assembly
IDA
PMID:28641114
A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Comp... 		KEEP AS NON CORE
Summary: Beta-catenin regulates synapse assembly via cadherin adhesion in neurons, a tissue-specific role distinct from core epithelial functions.
Reason: Neuronal process; IDA/IMP, non-core.
Supporting Evidence:
PMID:28641114
A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Complexes in Stabilizing Spines and Functional Synapses in the Neocortex.
GO:0097091 synaptic vesicle clustering
IMP
PMID:14622577
Role of beta-catenin in synaptic vesicle localization and pr... 		KEEP AS NON CORE
Summary: Beta-catenin organizes presynaptic vesicle clustering through cadherin-junction scaffolding at synapses; a downstream adhesion-linked synaptic role.
Reason: Vesicle clustering downstream of cadherin-adhesion scaffolding role.
Supporting Evidence:
PMID:14622577
Role of beta-catenin in synaptic vesicle localization and presynaptic assembly.
GO:0097091 synaptic vesicle clustering
IDA
PMID:14622577
Role of beta-catenin in synaptic vesicle localization and pr... 		KEEP AS NON CORE
Summary: Beta-catenin organizes presynaptic vesicle clustering through cadherin-junction scaffolding at synapses; a downstream adhesion-linked synaptic role.
Reason: Vesicle clustering downstream of cadherin-adhesion scaffolding role.
Supporting Evidence:
PMID:14622577
Role of beta-catenin in synaptic vesicle localization and presynaptic assembly.
GO:0098685 Schaffer collateral - CA1 synapse
IMP
PMID:14622577
Role of beta-catenin in synaptic vesicle localization and pr... 		KEEP AS NON CORE
Summary: Beta-catenin localizes to specific hippocampal CA1 synapses where it organizes synaptic adhesion, a tissue-restricted role distinct from its core junction/Wnt functions.
Reason: Synapse-specific neuronal localization; real (IDA/IMP) but peripheral.
Supporting Evidence:
PMID:14622577
Role of beta-catenin in synaptic vesicle localization and presynaptic assembly.
GO:0098685 Schaffer collateral - CA1 synapse
IDA
PMID:14622577
Role of beta-catenin in synaptic vesicle localization and pr... 		KEEP AS NON CORE
Summary: Beta-catenin localizes to specific hippocampal CA1 synapses where it organizes synaptic adhesion, a tissue-restricted role distinct from its core junction/Wnt functions.
Reason: Synapse-specific neuronal localization; real (IDA/IMP) but peripheral.
Supporting Evidence:
PMID:14622577
Role of beta-catenin in synaptic vesicle localization and presynaptic assembly.
GO:0098831 presynaptic active zone cytoplasmic component
IDA
PMID:8909549
The catenin/cadherin adhesion system is localized in synapti... 		KEEP AS NON CORE
Summary: Beta-catenin (with Scrib) localizes to the presynaptic active zone organizing vesicle clustering, a specialized neuronal role.
Reason: Synapse-specific localization; IDA, non-core.
Supporting Evidence:
PMID:8909549
The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones.
GO:0098978 glutamatergic synapse
IMP
PMID:28641114
A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Comp... 		KEEP AS NON CORE
Summary: Beta-catenin localizes to glutamatergic synapses where cadherin adhesion organizes synaptic structure, a neuron-specific role.
Reason: Synapse-specific localization; IDA/IMP, non-core.
Supporting Evidence:
PMID:28641114
A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Complexes in Stabilizing Spines and Functional Synapses in the Neocortex.
GO:0098978 glutamatergic synapse
IDA
PMID:28641114
A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Comp... 		KEEP AS NON CORE
Summary: Beta-catenin localizes to glutamatergic synapses where cadherin adhesion organizes synaptic structure, a neuron-specific role.
Reason: Synapse-specific localization; IDA/IMP, non-core.
Supporting Evidence:
PMID:28641114
A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Complexes in Stabilizing Spines and Functional Synapses in the Neocortex.
GO:0099092 postsynaptic density, intracellular component
IDA
PMID:8909549
The catenin/cadherin adhesion system is localized in synapti... 		KEEP AS NON CORE
Summary: Beta-catenin localizes to the postsynaptic density via cadherin-based synaptic adhesion; a localization reflecting its adhesion/scaffolding role rather than Wnt signaling.
Reason: PSD localization via cadherin adhesion role; non-core component annotation.
Supporting Evidence:
PMID:8909549
The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones.
GO:0048568 embryonic organ development
IMP
PMID:30478225
TBX2 and TBX3 act downstream of canonical WNT signaling in p... 		MARK AS OVER ANNOTATED
Summary: Broad embryonic-organ umbrella conveying nothing beta-catenin-specific; the many specific organ terms already capture its Wnt-driven developmental roles.
Reason: vague umbrella superseded by specific organ terms
Supporting Evidence:
PMID:30478225
TBX2 and TBX3 act downstream of canonical WNT signaling in patterning and differentiation of the mouse ureteric mesenchyme.
GO:0072497 mesenchymal stem cell differentiation
IMP
PMID:30478225
TBX2 and TBX3 act downstream of canonical WNT signaling in p... 		KEEP AS NON CORE
Summary: Beta-catenin directs MSC lineage choice (osteo/chondro/adipo) via Wnt/TCF transcription; a stem-cell fate outcome downstream of signaling.
Reason: downstream Wnt-driven MSC differentiation
Supporting Evidence:
PMID:30478225
TBX2 and TBX3 act downstream of canonical WNT signaling in patterning and differentiation of the mouse ureteric mesenchyme.
GO:0003713 transcription coactivator activity
IDA
PMID:15905404
Functional interaction between beta-catenin and FOXO in oxid... 		ACCEPT
Summary: The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.
Reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
Supporting Evidence:
PMID:15905404
Functional interaction between beta-catenin and FOXO in oxidative stress signaling.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0036520 astrocyte-dopaminergic neuron signaling
IMP
PMID:21752258
A Wnt1 regulated Frizzled-1/Ξ²-Catenin signaling pathway as a... 		KEEP AS NON CORE
Summary: Beta-catenin contributes to astrocyte-dopaminergic neuron crosstalk supporting midbrain DA neurogenesis; a niche-signaling outcome downstream of Wnt transcription.
Reason: downstream Wnt role in DA neuron niche signaling
Supporting Evidence:
PMID:21752258
A Wnt1 regulated Frizzled-1/Ξ²-Catenin signaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: Therapeutical relevance for neuron survival and neuroprotection.
GO:0060070 canonical Wnt signaling pathway
IMP
PMID:19122665
Wnt antagonism of Shh facilitates midbrain floor plate neuro... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:19122665
Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0060070 canonical Wnt signaling pathway
IMP
PMID:21752258
A Wnt1 regulated Frizzled-1/Ξ²-Catenin signaling pathway as a... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:21752258
A Wnt1 regulated Frizzled-1/Ξ²-Catenin signaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: Therapeutical relevance for neuron survival and neuroprotection.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0060070 canonical Wnt signaling pathway
IMP
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells a... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0003151 outflow tract morphogenesis
IMP
PMID:12464179
Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway m... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling in second-heart-field/neural-crest shapes the cardiac outflow tract; a downstream cardiac-morphogenesis phenotype.
Reason: Outflow tract morphogenesis downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:12464179
Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.
GO:0008284 positive regulation of cell population proliferation
IMP
PMID:12464179
Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway m... 		KEEP AS NON CORE
Summary: Beta-catenin drives proliferation via Wnt mitogenic targets (Myc, cyclin D1); a key but downstream consequence of its transcriptional coactivation.
Reason: Proliferation downstream of Wnt target genes Myc/CcnD1; non-core.
Supporting Evidence:
PMID:12464179
Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.
GO:1901331 positive regulation of odontoblast differentiation
IMP
PMID:29148101
Homeobox protein MSX-1 inhibits expression of bone morphogen... 		KEEP AS NON CORE
Summary: Beta-catenin promotes odontoblast differentiation via Wnt-target transcription in dental mesenchyme; a downstream lineage phenotype.
Reason: Odontoblast differentiation downstream of Wnt transcription.
Supporting Evidence:
PMID:29148101
Homeobox protein MSX-1 inhibits expression of bone morphogenetic protein 2, bone morphogenetic protein 4, and lymphoid enhancer-binding factor 1 via Wnt/Ξ²-catenin signaling to prevent differentiation of dental mesenchymal cells during the late bell stage.
GO:1903377 negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
IMP
PMID:21752258
A Wnt1 regulated Frizzled-1/Ξ²-Catenin signaling pathway as a... 		KEEP AS NON CORE
Summary: Beta-catenin attenuates oxidative-stress-triggered neuronal intrinsic apoptosis, likely through Wnt survival-gene output; a specific stress-protection phenotype.
Reason: Stress-specific neuroprotection downstream of Wnt transcription; non-core.
Supporting Evidence:
PMID:21752258
A Wnt1 regulated Frizzled-1/Ξ²-Catenin signaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: Therapeutical relevance for neuron survival and neuroprotection.
GO:0005515 protein binding
IPI
PMID:32533114
ADNP promotes neural differentiation by modulating Wnt/Ξ²-cat... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:32533114
ADNP promotes neural differentiation by modulating Wnt/Ξ²-catenin signaling.
GO:0003682 chromatin binding
IDA
PMID:16678101
Homeodomain-mediated beta-catenin-dependent switching events... 		ACCEPT
Summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
Reason: Core nuclear Wnt role; IDA/IGI-supported.
Supporting Evidence:
PMID:16678101
Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
GO:0003682 chromatin binding
IDA
PMID:16818445
Wnt9a signaling is required for joint integrity and regulati... 		ACCEPT
Summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
Reason: Core nuclear Wnt role; IDA/IGI-supported.
Supporting Evidence:
PMID:16818445
Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis.
GO:0003682 chromatin binding
IDA
PMID:17767158
Modulation of morphogenesis by noncanonical Wnt signaling re... 		ACCEPT
Summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
Reason: Core nuclear Wnt role; IDA/IGI-supported.
Supporting Evidence:
PMID:17767158
Modulation of morphogenesis by noncanonical Wnt signaling requires ATF/CREB family-mediated transcriptional activation of TGFbeta2.
GO:0003682 chromatin binding
IDA
PMID:19619491
Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-... 		ACCEPT
Summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
Reason: Core nuclear Wnt role; IDA/IGI-supported.
Supporting Evidence:
PMID:19619491
Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
GO:0003682 chromatin binding
IDA
PMID:19620969
A regulatory pathway involving Notch1/beta-catenin/Isl1 dete... 		ACCEPT
Summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
Reason: Core nuclear Wnt role; IDA/IGI-supported.
Supporting Evidence:
PMID:19620969
A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate.
GO:0003682 chromatin binding
IDA
PMID:19690384
Wnt signaling regulates smooth muscle precursor development ... 		ACCEPT
Summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
Reason: Core nuclear Wnt role; IDA/IGI-supported.
Supporting Evidence:
PMID:19690384
Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.
GO:0003682 chromatin binding
IDA
PMID:20159597
Characterization and in vivo pharmacological rescue of a Wnt... 		ACCEPT
Summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
Reason: Core nuclear Wnt role; IDA/IGI-supported.
Supporting Evidence:
PMID:20159597
Characterization and in vivo pharmacological rescue of a Wnt2-Gata6 pathway required for cardiac inflow tract development.
GO:0003682 chromatin binding
IDA
PMID:21350016
Canonical Wnt9b signaling balances progenitor cell expansion... 		ACCEPT
Summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
Reason: Core nuclear Wnt role; IDA/IGI-supported.
Supporting Evidence:
PMID:21350016
Canonical Wnt9b signaling balances progenitor cell expansion and differentiation during kidney development.
GO:0003682 chromatin binding
IDA
PMID:21512031
Hippo pathway inhibits Wnt signaling to restrain cardiomyocy... 		ACCEPT
Summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
Reason: Core nuclear Wnt role; IDA/IGI-supported.
Supporting Evidence:
PMID:21512031
Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size.
GO:0003682 chromatin binding
IGI
PMID:23824574
Wnt/Ξ²-catenin signalling regulates Sox17 expression and is e... 		ACCEPT
Summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
Reason: Core nuclear Wnt role; IDA/IGI-supported.
Supporting Evidence:
PMID:23824574
Wnt/Ξ²-catenin signalling regulates Sox17 expression and is essential for organizer and endoderm formation in the mouse.
GO:0003713 transcription coactivator activity
IDA
PMID:12235125
Beta-catenin-induced melanoma growth requires the downstream... 		ACCEPT
Summary: The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.
Reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
Supporting Evidence:
PMID:12235125
Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0003713 transcription coactivator activity
IDA
PMID:12464179
Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway m... 		ACCEPT
Summary: The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.
Reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
Supporting Evidence:
PMID:12464179
Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0003713 transcription coactivator activity
IDA
PMID:16678101
Homeodomain-mediated beta-catenin-dependent switching events... 		ACCEPT
Summary: The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.
Reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
Supporting Evidence:
PMID:16678101
Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0003713 transcription coactivator activity
IDA
PMID:19056892
A functional link between Wnt signaling and SKP2-independent... 		ACCEPT
Summary: The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.
Reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
Supporting Evidence:
PMID:19056892
A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0003713 transcription coactivator activity
IMP
PMID:19619491
Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-... 		ACCEPT
Summary: The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.
Reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
Supporting Evidence:
PMID:19619491
Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005515 protein binding
IPI
PMID:10318824
Functional domains of axin. Importance of the C terminus as ... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:10318824
Functional domains of axin. Importance of the C terminus as an oligomerization domain.
GO:0005515 protein binding
IPI
PMID:11104755
Substitution of a glycogen synthase kinase-3beta phosphoryla... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:11104755
Substitution of a glycogen synthase kinase-3beta phosphorylation site in presenilin 1 separates presenilin function from beta-catenin signaling.
GO:0005515 protein binding
IPI
PMID:12432063
Protein kinase CKII regulates the interaction of beta-cateni... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:12432063
Protein kinase CKII regulates the interaction of beta-catenin with alpha-catenin and its protein stability.
GO:0005515 protein binding
IPI
PMID:12695331
NF2 deficiency promotes tumorigenesis and metastasis by dest... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:12695331
NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions.
GO:0005515 protein binding
IPI
PMID:12861022
T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, s... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:12861022
T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors.
GO:0005515 protein binding
IPI
PMID:14647292
Mammalian formin-1 participates in adherens junctions and po... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:14647292
Mammalian formin-1 participates in adherens junctions and polymerization of linear actin cables.
GO:0005515 protein binding
IPI
PMID:14960280
Ozz-E3, a muscle-specific ubiquitin ligase, regulates beta-c... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:14960280
Ozz-E3, a muscle-specific ubiquitin ligase, regulates beta-catenin degradation during myogenesis.
GO:0005515 protein binding
IPI
PMID:15574752
Role of a BCL9-related beta-catenin-binding protein, B9L, in... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:15574752
Role of a BCL9-related beta-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling.
GO:0005515 protein binding
IPI
PMID:15781477
Sox2 induction by FGF and FGFR2 activating mutations inhibit... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:15781477
Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation.
GO:0005515 protein binding
IPI
PMID:15834408
The KIF3 motor transports N-cadherin and organizes the devel... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:15834408
The KIF3 motor transports N-cadherin and organizes the developing neuroepithelium.
GO:0005515 protein binding
IPI
PMID:16368433
Deficient E-cadherin adhesion in C57BL/6J-Min/+ mice is asso... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:16368433
Deficient E-cadherin adhesion in C57BL/6J-Min/+ mice is associated with increased tyrosine kinase activity and RhoA-dependent actomyosin contractility.
GO:0005515 protein binding
IPI
PMID:17535849
A unique and specific interaction between alphaT-catenin and... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:17535849
A unique and specific interaction between alphaT-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs.
GO:0005515 protein binding
IPI
PMID:18202148
Cooperative control via lymphoid enhancer factor 1/T cell fa... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:18202148
Cooperative control via lymphoid enhancer factor 1/T cell factor 3 and estrogen receptor-alpha for uterine gene regulation by estrogen.
GO:0005515 protein binding
IPI
PMID:18632848
SUMOylation target sites at the C terminus protect Axin from... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:18632848
SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability.
GO:0005515 protein binding
IPI
PMID:19503085
HDAC1 and HDAC2 regulate oligodendrocyte differentiation by ... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:19503085
HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction.
GO:0005515 protein binding
IPI
PMID:19725955
Arginine methyltransferase CARM1/PRMT4 regulates endochondra... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:19725955
Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification.
GO:0005515 protein binding
IPI
PMID:21512031
Hippo pathway inhibits Wnt signaling to restrain cardiomyocy... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:21512031
Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size.
GO:0005515 protein binding
IPI
PMID:22665494
mrhl RNA, a long noncoding RNA, negatively regulates Wnt sig... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:22665494
mrhl RNA, a long noncoding RNA, negatively regulates Wnt signaling through its protein partner Ddx5/p68 in mouse spermatogonial cells.
GO:0005515 protein binding
IPI
PMID:26787558
SPECC1L deficiency results in increased adherens junction st... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:26787558
SPECC1L deficiency results in increased adherens junction stability and reduced cranial neural crest cell delamination.
GO:0005515 protein binding
IPI
PMID:30659184
Hematopoietic PBX-interacting protein mediates cartilage deg... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:30659184
Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis.
GO:0005515 protein binding
IPI
PMID:8555428
Immunotoxicologic effects of ethylene dibromide in the mouse... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:8555428
Immunotoxicologic effects of ethylene dibromide in the mouse and their modulation by the estrous cycle.
GO:0005515 protein binding
IPI
PMID:9488439
Two members of the Tcf family implicated in Wnt/beta-catenin... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:9488439
Two members of the Tcf family implicated in Wnt/beta-catenin signaling during embryogenesis in the mouse.
GO:0005515 protein binding
IPI
PMID:9554852
Functional interaction of an axin homolog, conductin, with b... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:9554852
Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta.
GO:0005634 nucleus
IPI
PMID:30659184
Hematopoietic PBX-interacting protein mediates cartilage deg... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:30659184
Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis.
GO:0005634 nucleus
IDA
PMID:11731231
Dynamic expression and nuclear accumulation of beta-catenin ... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:11731231
Dynamic expression and nuclear accumulation of beta-catenin during the development of hair follicle-derived structures.
GO:0005634 nucleus
IDA
PMID:11731265
Expression of Tcf/Lef and sFrp and localization of beta-cate... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:11731265
Expression of Tcf/Lef and sFrp and localization of beta-catenin in the developing mouse lung.
GO:0005634 nucleus
IDA
PMID:11872843
Colorectal cancer in mice genetically deficient in the mucin... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:11872843
Colorectal cancer in mice genetically deficient in the mucin Muc2.
GO:0005634 nucleus
IDA
PMID:12874278
The PDZ protein tax-interacting protein-1 inhibits beta-cate... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:12874278
The PDZ protein tax-interacting protein-1 inhibits beta-catenin transcriptional activity and growth of colorectal cancer cells.
GO:0005634 nucleus
IDA
PMID:12885771
beta-Catenin is required for specification of proximal/dista... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:12885771
beta-Catenin is required for specification of proximal/distal cell fate during lung morphogenesis.
GO:0005634 nucleus
IDA
PMID:12923052
Genetic interaction between Wnt/beta-catenin and BMP recepto... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:12923052
Genetic interaction between Wnt/beta-catenin and BMP receptor signaling during formation of the AER and the dorsal-ventral axis in the limb.
GO:0005634 nucleus
IDA
PMID:15371327
Wnt/beta-catenin signaling is sufficient and necessary for s... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:15371327
Wnt/beta-catenin signaling is sufficient and necessary for synovial joint formation.
GO:0005634 nucleus
IDA
PMID:15574752
Role of a BCL9-related beta-catenin-binding protein, B9L, in... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:15574752
Role of a BCL9-related beta-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling.
GO:0005634 nucleus
IDA
PMID:15778706
Wnt signalling induces maturation of Paneth cells in intesti... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:15778706
Wnt signalling induces maturation of Paneth cells in intestinal crypts.
GO:0005634 nucleus
IDA
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts fr... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
GO:0005634 nucleus
IDA
PMID:15866165
Canonical Wnt signaling in differentiated osteoblasts contro... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:15866165
Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
GO:0005634 nucleus
IDA
PMID:16439479
Foxf1 and Foxf2 control murine gut development by limiting m... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:16439479
Foxf1 and Foxf2 control murine gut development by limiting mesenchymal Wnt signaling and promoting extracellular matrix production.
GO:0005634 nucleus
IDA
PMID:16489008
Patched1 functions as a gatekeeper by promoting cell cycle p... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:16489008
Patched1 functions as a gatekeeper by promoting cell cycle progression.
GO:0005634 nucleus
IDA
PMID:16678815
Lef1 is required for the transition of Wnt signaling from me... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:16678815
Lef1 is required for the transition of Wnt signaling from mesenchymal to epithelial cells in the mouse embryonic mammary gland.
GO:0005634 nucleus
IDA
PMID:16858399
C3G regulates the size of the cerebral cortex neural precurs... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:16858399
C3G regulates the size of the cerebral cortex neural precursor population.
GO:0005634 nucleus
IDA
PMID:16989802
Levels of mesenchymal FGFR2 signaling modulate smooth muscle... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:16989802
Levels of mesenchymal FGFR2 signaling modulate smooth muscle progenitor cell commitment in the lung.
GO:0005634 nucleus
IDA
PMID:17128274
Wnt-beta-catenin signaling initiates taste papilla developme... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:17128274
Wnt-beta-catenin signaling initiates taste papilla development.
GO:0005634 nucleus
IDA
PMID:17560563
Fgf10 dosage is critical for the amplification of epithelial... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:17560563
Fgf10 dosage is critical for the amplification of epithelial cell progenitors and for the formation of multiple mesenchymal lineages during lung development.
GO:0005634 nucleus
IDA
PMID:17596282
Unique mechanisms of growth regulation and tumor suppression... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:17596282
Unique mechanisms of growth regulation and tumor suppression upon Apc inactivation in the pancreas.
GO:0005634 nucleus
IDA
PMID:17615359
Regulation of spontaneous intestinal tumorigenesis through t... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:17615359
Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88.
GO:0005634 nucleus
IDA
PMID:18978355
Overexpression of TEAD-1 in transgenic mouse striated muscle... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:18978355
Overexpression of TEAD-1 in transgenic mouse striated muscles produces a slower skeletal muscle contractile phenotype.
GO:0005634 nucleus
IDA
PMID:19213727
Wnt11 promotes osteoblast maturation and mineralization thro... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:19213727
Wnt11 promotes osteoblast maturation and mineralization through R-spondin 2.
GO:0005634 nucleus
IDA
PMID:19497282
Wnt7a activates the planar cell polarity pathway to drive th... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:19497282
Wnt7a activates the planar cell polarity pathway to drive the symmetric expansion of satellite stem cells.
GO:0005634 nucleus
IDA
PMID:19796622
Uncovering early response of gene regulatory networks in ESC... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:19796622
Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors.
GO:0005634 nucleus
IDA
PMID:19850029
A critical role for sFRP proteins in maintaining caudal neur... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:19850029
A critical role for sFRP proteins in maintaining caudal neural tube closure in mice via inhibition of BMP signaling.
GO:0005634 nucleus
IDA
PMID:21991325
RSPO1/Ξ²-catenin signaling pathway regulates oogonia differen... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:21991325
RSPO1/Ξ²-catenin signaling pathway regulates oogonia differentiation and entry into meiosis in the mouse fetal ovary.
GO:0005634 nucleus
IDA
PMID:22665494
mrhl RNA, a long noncoding RNA, negatively regulates Wnt sig... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:22665494
mrhl RNA, a long noncoding RNA, negatively regulates Wnt signaling through its protein partner Ddx5/p68 in mouse spermatogonial cells.
GO:0005634 nucleus
IDA
PMID:23266329
Kruppel-like factor 5 controls villus formation and initiati... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:23266329
Kruppel-like factor 5 controls villus formation and initiation of cytodifferentiation in the embryonic intestinal epithelium.
GO:0005634 nucleus
IDA
PMID:23610556
A positive feedback loop involving Gcm1 and Fzd5 directs cho... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:23610556
A positive feedback loop involving Gcm1 and Fzd5 directs chorionic branching morphogenesis in the placenta.
GO:0005634 nucleus
IDA
PMID:23740243
Activation of the transcription factor GLI1 by WNT signaling... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:23740243
Activation of the transcription factor GLI1 by WNT signaling underlies the role of SULFATASE 2 as a regulator of tissue regeneration.
GO:0005634 nucleus
IDA
PMID:25535395
Notch inhibition induces mitotically generated hair cells in... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:25535395
Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway.
GO:0005634 nucleus
IDA
PMID:30659184
Hematopoietic PBX-interacting protein mediates cartilage deg... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:30659184
Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis.
GO:0005634 nucleus
IDA
PMID:31222549
The Shisa3 knockout mouse exhibits normal bone phenotype. 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:31222549
The Shisa3 knockout mouse exhibits normal bone phenotype.
GO:0005667 transcription regulator complex
IDA
PMID:12464179
Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway m... 		ACCEPT
Summary: Beta-catenin is a component of transcription regulator complexes (with TCF/LEF and coactivators) that drive Wnt target gene expression.
Reason: Core nuclear Wnt effector complex; IDA-supported.
Supporting Evidence:
PMID:12464179
Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.
GO:0005667 transcription regulator complex
IDA
PMID:12861022
T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, s... 		ACCEPT
Summary: Beta-catenin is a component of transcription regulator complexes (with TCF/LEF and coactivators) that drive Wnt target gene expression.
Reason: Core nuclear Wnt effector complex; IDA-supported.
Supporting Evidence:
PMID:12861022
T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors.
GO:0005667 transcription regulator complex
IDA
PMID:16678101
Homeodomain-mediated beta-catenin-dependent switching events... 		ACCEPT
Summary: Beta-catenin is a component of transcription regulator complexes (with TCF/LEF and coactivators) that drive Wnt target gene expression.
Reason: Core nuclear Wnt effector complex; IDA-supported.
Supporting Evidence:
PMID:16678101
Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
GO:0005737 cytoplasm
IPI
PMID:30659184
Hematopoietic PBX-interacting protein mediates cartilage deg... 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:30659184
Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis.
GO:0005737 cytoplasm
IDA
PMID:11731231
Dynamic expression and nuclear accumulation of beta-catenin ... 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:11731231
Dynamic expression and nuclear accumulation of beta-catenin during the development of hair follicle-derived structures.
GO:0005737 cytoplasm
IDA
PMID:11731265
Expression of Tcf/Lef and sFrp and localization of beta-cate... 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:11731265
Expression of Tcf/Lef and sFrp and localization of beta-catenin in the developing mouse lung.
GO:0005737 cytoplasm
IDA
PMID:12235125
Beta-catenin-induced melanoma growth requires the downstream... 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:12235125
Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor.
GO:0005737 cytoplasm
IDA
PMID:12923052
Genetic interaction between Wnt/beta-catenin and BMP recepto... 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:12923052
Genetic interaction between Wnt/beta-catenin and BMP receptor signaling during formation of the AER and the dorsal-ventral axis in the limb.
GO:0005737 cytoplasm
IDA
PMID:14981260
Nuclear-cytoplasmic shuttling of Axin regulates subcellular ... 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:14981260
Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of beta-catenin.
GO:0005737 cytoplasm
IDA
PMID:15525667
Stabilization of beta-catenin in the mouse zygote leads to p... 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:15525667
Stabilization of beta-catenin in the mouse zygote leads to premature epithelial-mesenchymal transition in the epiblast.
GO:0005737 cytoplasm
IDA
PMID:15574752
Role of a BCL9-related beta-catenin-binding protein, B9L, in... 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:15574752
Role of a BCL9-related beta-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling.
GO:0005737 cytoplasm
IDA
PMID:16489008
Patched1 functions as a gatekeeper by promoting cell cycle p... 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:16489008
Patched1 functions as a gatekeeper by promoting cell cycle progression.
GO:0005737 cytoplasm
IDA
PMID:17128274
Wnt-beta-catenin signaling initiates taste papilla developme... 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:17128274
Wnt-beta-catenin signaling initiates taste papilla development.
GO:0005737 cytoplasm
IDA
PMID:19213727
Wnt11 promotes osteoblast maturation and mineralization thro... 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:19213727
Wnt11 promotes osteoblast maturation and mineralization through R-spondin 2.
GO:0005737 cytoplasm
IDA
PMID:30659184
Hematopoietic PBX-interacting protein mediates cartilage deg... 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:30659184
Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis.
GO:0005829 cytosol
IDA
PMID:12055200
Regulation of Wnt signaling during adipogenesis. 		ACCEPT
Summary: Beta-catenin has a cytosolic pool subject to destruction-complex regulation and Wnt-dependent stabilization.
Reason: Genuine pool; IDA/TAS-supported.
Supporting Evidence:
PMID:12055200
Regulation of Wnt signaling during adipogenesis.
GO:0005829 cytosol
IDA
PMID:15673614
Wnt10b deficiency promotes coexpression of myogenic and adip... 		ACCEPT
Summary: Beta-catenin has a cytosolic pool subject to destruction-complex regulation and Wnt-dependent stabilization.
Reason: Genuine pool; IDA/TAS-supported.
Supporting Evidence:
PMID:15673614
Wnt10b deficiency promotes coexpression of myogenic and adipogenic programs in myoblasts.
GO:0005886 plasma membrane
IDA
PMID:12040017
Mouse mammary epithelial cells express the Na-K-Cl cotranspo... 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
Supporting Evidence:
PMID:12040017
Mouse mammary epithelial cells express the Na-K-Cl cotransporter, NKCC1: characterization, localization, and involvement in ductal development and morphogenesis.
GO:0005886 plasma membrane
IDA
PMID:16418220
Desmocollin 3 is required for pre-implantation development o... 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
Supporting Evidence:
PMID:16418220
Desmocollin 3 is required for pre-implantation development of the mouse embryo.
GO:0005886 plasma membrane
IDA
PMID:16740478
Apc tumor suppressor gene is the "zonation-keeper" of mouse ... 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
Supporting Evidence:
PMID:16740478
Apc tumor suppressor gene is the "zonation-keeper" of mouse liver.
GO:0005886 plasma membrane
IDA
PMID:16858399
C3G regulates the size of the cerebral cortex neural precurs... 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
Supporting Evidence:
PMID:16858399
C3G regulates the size of the cerebral cortex neural precursor population.
GO:0005886 plasma membrane
IDA
PMID:16962386
Tissue, cellular and sub-cellular localization of the Vangl2... 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
Supporting Evidence:
PMID:16962386
Tissue, cellular and sub-cellular localization of the Vangl2 protein during embryonic development: effect of the Lp mutation.
GO:0005886 plasma membrane
IDA
PMID:17596282
Unique mechanisms of growth regulation and tumor suppression... 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
Supporting Evidence:
PMID:17596282
Unique mechanisms of growth regulation and tumor suppression upon Apc inactivation in the pancreas.
GO:0005886 plasma membrane
IDA
PMID:19966784
Sec24b selectively sorts Vangl2 to regulate planar cell pola... 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
Supporting Evidence:
PMID:19966784
Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closure.
GO:0005886 plasma membrane
IDA
PMID:23266329
Kruppel-like factor 5 controls villus formation and initiati... 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
Supporting Evidence:
PMID:23266329
Kruppel-like factor 5 controls villus formation and initiation of cytodifferentiation in the embryonic intestinal epithelium.
GO:0005886 plasma membrane
IDA
PMID:8853988
Expression and cell membrane localization of catenins during... 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
Supporting Evidence:
PMID:8853988
Expression and cell membrane localization of catenins during mouse preimplantation development.
GO:0005911 cell-cell junction
IDA
PMID:12181493
TCL1 participates in early embryonic development and is over... 		ACCEPT
Summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
Reason: Core junctional localization; IDA.
Supporting Evidence:
PMID:12181493
TCL1 participates in early embryonic development and is overexpressed in human seminomas.
GO:0005911 cell-cell junction
IDA
PMID:14597196
Overexpression of Sonic Hedgehog suppresses embryonic hair f... 		ACCEPT
Summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
Reason: Core junctional localization; IDA.
Supporting Evidence:
PMID:14597196
Overexpression of Sonic Hedgehog suppresses embryonic hair follicle morphogenesis.
GO:0005911 cell-cell junction
IDA
PMID:18816447
Diverse roles of E-cadherin in the morphogenesis of the subm... 		ACCEPT
Summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
Reason: Core junctional localization; IDA.
Supporting Evidence:
PMID:18816447
Diverse roles of E-cadherin in the morphogenesis of the submandibular gland: insights into the formation of acinar and ductal structures.
GO:0005911 cell-cell junction
ISO
PMID:19151727
Regulation of cardiovascular development and integrity by th... 		ACCEPT
Summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
Reason: Core junctional localization; IDA.
Supporting Evidence:
PMID:19151727
Regulation of cardiovascular development and integrity by the heart of glass-cerebral cavernous malformation protein pathway.
GO:0005911 cell-cell junction
IDA
PMID:20089884
Milk secretion and ejection are impaired in the mammary glan... 		ACCEPT
Summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
Reason: Core junctional localization; IDA.
Supporting Evidence:
PMID:20089884
Milk secretion and ejection are impaired in the mammary gland of mice harboring a Cx43 mutant while expression and localization of tight and adherens junction proteins remain unchanged.
GO:0005911 cell-cell junction
IDA
PMID:21377456
Grainyhead-like 2 regulates neural tube closure and adhesion... 		ACCEPT
Summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
Reason: Core junctional localization; IDA.
Supporting Evidence:
PMID:21377456
Grainyhead-like 2 regulates neural tube closure and adhesion molecule expression during neural fold fusion.
GO:0005911 cell-cell junction
IDA
PMID:24191021
Sox9 plays multiple roles in the lung epithelium during bran... 		ACCEPT
Summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
Reason: Core junctional localization; IDA.
Supporting Evidence:
PMID:24191021
Sox9 plays multiple roles in the lung epithelium during branching morphogenesis.
GO:0005911 cell-cell junction
IDA
PMID:9950951
Nuclear localization of beta-catenin and loss of apical brus... 		ACCEPT
Summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
Reason: Core junctional localization; IDA.
Supporting Evidence:
PMID:9950951
Nuclear localization of beta-catenin and loss of apical brush border actin in cystic tubules of bcl-2 -/- mice.
GO:0005912 adherens junction
IDA
PMID:11731229
FAM deubiquitylating enzyme is essential for preimplantation... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:11731229
FAM deubiquitylating enzyme is essential for preimplantation mouse embryo development.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005912 adherens junction
IDA
PMID:12203715
Localization of the novel Xin protein to the adherens juncti... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:12203715
Localization of the novel Xin protein to the adherens junction complex in cardiac and skeletal muscle during development.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005912 adherens junction
IDA
PMID:12695331
NF2 deficiency promotes tumorigenesis and metastasis by dest... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:12695331
NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005912 adherens junction
IDA
PMID:14657280
Lamellipodium extension and cadherin adhesion: two cell resp... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:14657280
Lamellipodium extension and cadherin adhesion: two cell responses to cadherin activation relying on distinct signalling pathways.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005912 adherens junction
IDA
PMID:15148305
Mammalian Fat1 cadherin regulates actin dynamics and cell-ce... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:15148305
Mammalian Fat1 cadherin regulates actin dynamics and cell-cell contact.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005912 adherens junction
IDA
PMID:15292239
Defects in cell adhesion and the visceral endoderm following... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:15292239
Defects in cell adhesion and the visceral endoderm following ablation of nonmuscle myosin heavy chain II-A in mice.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005912 adherens junction
IDA
PMID:15645444
Gene expression profile analysis of mouse colon embryonic de... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:15645444
Gene expression profile analysis of mouse colon embryonic development.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005912 adherens junction
IDA
PMID:15775979
E-cadherin is essential for in vivo epidermal barrier functi... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:15775979
E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005912 adherens junction
IDA
PMID:16199027
Vezatin, a protein associated to adherens junctions, is requ... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:16199027
Vezatin, a protein associated to adherens junctions, is required for mouse blastocyst morphogenesis.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005912 adherens junction
IDA
PMID:16892058
The Rho-GTPase cdc42 regulates neural progenitor fate at the... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:16892058
The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005912 adherens junction
IDA
PMID:17544522
Targeted disruption of the murine large nuclear KIAA1440/Int... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:17544522
Targeted disruption of the murine large nuclear KIAA1440/Ints1 protein causes growth arrest in early blastocyst stage embryos and eventual apoptotic cell death.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005912 adherens junction
IDA
PMID:21991385
Adhesion protein VSIG1 is required for the proper differenti... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:21991385
Adhesion protein VSIG1 is required for the proper differentiation of glandular gastric epithelia.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005912 adherens junction
IDA
PMID:23824574
Wnt/Ξ²-catenin signalling regulates Sox17 expression and is e... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:23824574
Wnt/Ξ²-catenin signalling regulates Sox17 expression and is essential for organizer and endoderm formation in the mouse.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005912 adherens junction
IDA
PMID:26787558
SPECC1L deficiency results in increased adherens junction st... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:26787558
SPECC1L deficiency results in increased adherens junction stability and reduced cranial neural crest cell delamination.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005912 adherens junction
IDA
PMID:29211732
The mouse Jhy gene regulates ependymal cell differentiation ... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:29211732
The mouse Jhy gene regulates ependymal cell differentiation and ciliogenesis.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005916 fascia adherens
IDA
PMID:16481394
The transitional junction: a new functional subcellular doma... 		ACCEPT
Summary: Beta-catenin is a core structural component of the fascia adherens, linking N-cadherin to actin at cardiac intercalated-disc junctions (IDA); a direct adhesion-structure localization.
Reason: direct structural localization at adherens junction
Supporting Evidence:
PMID:16481394
The transitional junction: a new functional subcellular domain at the intercalated disc.
GO:0005923 bicellular tight junction
IDA
PMID:17130295
Distinct subdomain organization and molecular composition of... 		KEEP AS NON CORE
Summary: Beta-catenin is detected near tight junctions through junctional crosstalk, but tight junctions are not its primary structural site (adherens junctions are).
Reason: Adjacent-junction localization; IDA but non-core.
Supporting Evidence:
PMID:17130295
Distinct subdomain organization and molecular composition of a tight junction with adherens junction features.
GO:0014704 intercalated disc
IDA
PMID:17535849
A unique and specific interaction between alphaT-catenin and... 		ACCEPT
Summary: Beta-catenin is a core structural component of the cardiac intercalated disc, anchoring N-cadherin to the actin cytoskeleton (IDA/ISO); a direct adhesion-structure localization.
Reason: direct structural localization at cardiac junction
Supporting Evidence:
PMID:17535849
A unique and specific interaction between alphaT-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs.
GO:0016020 membrane
IDA
PMID:11731231
Dynamic expression and nuclear accumulation of beta-catenin ... 		KEEP AS NON CORE
Summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
Reason: Over-general CC parent.
Supporting Evidence:
PMID:11731231
Dynamic expression and nuclear accumulation of beta-catenin during the development of hair follicle-derived structures.
GO:0016020 membrane
IDA
PMID:12055200
Regulation of Wnt signaling during adipogenesis. 		KEEP AS NON CORE
Summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
Reason: Over-general CC parent.
Supporting Evidence:
PMID:12055200
Regulation of Wnt signaling during adipogenesis.
GO:0016020 membrane
IDA
PMID:12432063
Protein kinase CKII regulates the interaction of beta-cateni... 		KEEP AS NON CORE
Summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
Reason: Over-general CC parent.
Supporting Evidence:
PMID:12432063
Protein kinase CKII regulates the interaction of beta-catenin with alpha-catenin and its protein stability.
GO:0016020 membrane
IDA
PMID:12611902
Regulation of the SHP-2 tyrosine phosphatase by a novel chol... 		KEEP AS NON CORE
Summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
Reason: Over-general CC parent.
Supporting Evidence:
PMID:12611902
Regulation of the SHP-2 tyrosine phosphatase by a novel cholesterol- and cell confluence-dependent mechanism.
GO:0016020 membrane
IDA
PMID:14657280
Lamellipodium extension and cadherin adhesion: two cell resp... 		KEEP AS NON CORE
Summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
Reason: Over-general CC parent.
Supporting Evidence:
PMID:14657280
Lamellipodium extension and cadherin adhesion: two cell responses to cadherin activation relying on distinct signalling pathways.
GO:0016020 membrane
IDA
PMID:15987773
Forkhead box A1 regulates prostate ductal morphogenesis and ... 		KEEP AS NON CORE
Summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
Reason: Over-general CC parent.
Supporting Evidence:
PMID:15987773
Forkhead box A1 regulates prostate ductal morphogenesis and promotes epithelial cell maturation.
GO:0016020 membrane
IDA
PMID:16364283
Hex homeobox gene controls the transition of the endoderm to... 		KEEP AS NON CORE
Summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
Reason: Over-general CC parent.
Supporting Evidence:
PMID:16364283
Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development.
GO:0016020 membrane
IDA
PMID:21991325
RSPO1/Ξ²-catenin signaling pathway regulates oogonia differen... 		KEEP AS NON CORE
Summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
Reason: Over-general CC parent.
Supporting Evidence:
PMID:21991325
RSPO1/Ξ²-catenin signaling pathway regulates oogonia differentiation and entry into meiosis in the mouse fetal ovary.
GO:0016020 membrane
IDA
PMID:22139371
Bardet-Biedl syndrome 3 (Bbs3) knockout mouse model reveals ... 		KEEP AS NON CORE
Summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
Reason: Over-general CC parent.
Supporting Evidence:
PMID:22139371
Bardet-Biedl syndrome 3 (Bbs3) knockout mouse model reveals common BBS-associated phenotypes and Bbs3 unique phenotypes.
GO:0016020 membrane
IDA
PMID:8821035
Expression of catenins during mouse embryonic development an... 		KEEP AS NON CORE
Summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
Reason: Over-general CC parent.
Supporting Evidence:
PMID:8821035
Expression of catenins during mouse embryonic development and in adult tissues.
GO:0016323 basolateral plasma membrane
IDA
PMID:12885771
beta-Catenin is required for specification of proximal/dista... 		ACCEPT
Summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
Reason: Genuine junctional pool; IDA-supported.
Supporting Evidence:
PMID:12885771
beta-Catenin is required for specification of proximal/distal cell fate during lung morphogenesis.
GO:0016323 basolateral plasma membrane
IDA
PMID:14625387
Foxj1 is required for apical localization of ezrin in airway... 		ACCEPT
Summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
Reason: Genuine junctional pool; IDA-supported.
Supporting Evidence:
PMID:14625387
Foxj1 is required for apical localization of ezrin in airway epithelial cells.
GO:0016323 basolateral plasma membrane
IDA
PMID:15226261
Orpk mouse model of polycystic kidney disease reveals essent... 		ACCEPT
Summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
Reason: Genuine junctional pool; IDA-supported.
Supporting Evidence:
PMID:15226261
Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization.
GO:0016323 basolateral plasma membrane
IDA
PMID:17671182
Haploinsufficiency of KrΓΌppel-like factor 4 promotes adenoma... 		ACCEPT
Summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
Reason: Genuine junctional pool; IDA-supported.
Supporting Evidence:
PMID:17671182
Haploinsufficiency of KrΓΌppel-like factor 4 promotes adenomatous polyposis coli dependent intestinal tumorigenesis.
GO:0016323 basolateral plasma membrane
IDA
PMID:20016102
The small GTPase Rac1 regulates auditory hair cell morphogen... 		ACCEPT
Summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
Reason: Genuine junctional pool; IDA-supported.
Supporting Evidence:
PMID:20016102
The small GTPase Rac1 regulates auditory hair cell morphogenesis.
GO:0016323 basolateral plasma membrane
IDA
PMID:20089884
Milk secretion and ejection are impaired in the mammary glan... 		ACCEPT
Summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
Reason: Genuine junctional pool; IDA-supported.
Supporting Evidence:
PMID:20089884
Milk secretion and ejection are impaired in the mammary gland of mice harboring a Cx43 mutant while expression and localization of tight and adherens junction proteins remain unchanged.
GO:0016323 basolateral plasma membrane
IDA
PMID:9950951
Nuclear localization of beta-catenin and loss of apical brus... 		ACCEPT
Summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
Reason: Genuine junctional pool; IDA-supported.
Supporting Evidence:
PMID:9950951
Nuclear localization of beta-catenin and loss of apical brush border actin in cystic tubules of bcl-2 -/- mice.
GO:0016327 apicolateral plasma membrane
IDA
PMID:29211732
The mouse Jhy gene regulates ependymal cell differentiation ... 		ACCEPT
Summary: Beta-catenin concentrates at the apicolateral membrane where adherens junctions form between polarized epithelial cells.
Reason: Genuine junctional membrane localization; IDA.
Supporting Evidence:
PMID:29211732
The mouse Jhy gene regulates ependymal cell differentiation and ciliogenesis.
GO:0016328 lateral plasma membrane
ISO
GO_REF:0000008 		ACCEPT
Summary: Beta-catenin concentrates at the lateral membrane of epithelia where cadherin-based cell-cell junctions assemble.
Reason: Genuine core junctional membrane pool; IDA.
GO:0016328 lateral plasma membrane
IDA
PMID:15645444
Gene expression profile analysis of mouse colon embryonic de... 		ACCEPT
Summary: Beta-catenin concentrates at the lateral membrane of epithelia where cadherin-based cell-cell junctions assemble.
Reason: Genuine core junctional membrane pool; IDA.
Supporting Evidence:
PMID:15645444
Gene expression profile analysis of mouse colon embryonic development.
GO:0016342 catenin complex
IDA
PMID:8853988
Expression and cell membrane localization of catenins during... 		ACCEPT
Summary: Beta-catenin is a defining member of the catenin (cadherin-catenin) complex linking cadherins to alpha-catenin/actin.
Reason: Core complex; broadly supported (IBA/IDA/IMP/ISS).
Supporting Evidence:
PMID:8853988
Expression and cell membrane localization of catenins during mouse preimplantation development.
GO:0030018 Z disc
IDA
PMID:8821035
Expression of catenins during mouse embryonic development an... 		KEEP AS NON CORE
Summary: Beta-catenin localizes to the cardiomyocyte Z disc/intercalated-disc region, a muscle-specific adhesion structure secondary to its general adherens-junction role.
Reason: Tissue-specific (muscle) localization; IDA but non-core.
Supporting Evidence:
PMID:8821035
Expression of catenins during mouse embryonic development and in adult tissues.
GO:0030027 lamellipodium
IDA
PMID:14657280
Lamellipodium extension and cadherin adhesion: two cell resp... 		KEEP AS NON CORE
Summary: A lamellipodial pool reflects beta-catenin at dynamic actin-rich protrusions, secondary to its stable junctional localization.
Reason: Context-specific localization; IDA, non-core.
Supporting Evidence:
PMID:14657280
Lamellipodium extension and cadherin adhesion: two cell responses to cadherin activation relying on distinct signalling pathways.
GO:0030877 beta-catenin destruction complex
IDA
PMID:10318824
Functional domains of axin. Importance of the C terminus as ... 		ACCEPT
Summary: In the absence of Wnt, beta-catenin is the substrate within the AXIN/APC/GSK3B/CK1 destruction complex that drives its phosphorylation and degradation.
Reason: Core Wnt regulation; defining complex membership (IDA/ISS).
Supporting Evidence:
PMID:10318824
Functional domains of axin. Importance of the C terminus as an oligomerization domain.
GO:0031253 cell projection membrane
IDA
PMID:16621792
Membrane localization of adenomatous polyposis coli protein ... 		KEEP AS NON CORE
Summary: Localization to cell-projection membranes (e.g. neuronal processes) is a specialized pool secondary to beta-catenin's epithelial junction role.
Reason: Context-specific membrane pool; IDA but peripheral.
Supporting Evidence:
PMID:16621792
Membrane localization of adenomatous polyposis coli protein at cellular protrusions: targeting sequences and regulation by beta-catenin.
GO:0031528 microvillus membrane
IDA
PMID:16439479
Foxf1 and Foxf2 control murine gut development by limiting m... 		KEEP AS NON CORE
Summary: A microvillus-membrane pool is a specialized apical localization in particular epithelia, secondary to core junctional pools.
Reason: Tissue-specific localization; IDA, non-core.
Supporting Evidence:
PMID:16439479
Foxf1 and Foxf2 control murine gut development by limiting mesenchymal Wnt signaling and promoting extracellular matrix production.
GO:0032991 protein-containing complex
ISO
PMID:22083958
Histone H1 recruitment by CHD8 is essential for suppression ... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein-containing complex' is uninformative; beta-catenin's specific complexes (catenin, TCF, destruction) are annotated separately.
Reason: Generic CC over-annotation.
Supporting Evidence:
PMID:22083958
Histone H1 recruitment by CHD8 is essential for suppression of the Wnt-Ξ²-catenin signaling pathway.
GO:0043296 apical junction complex
IDA
PMID:16249236
Shroom regulates epithelial cell shape via the apical positi... 		ACCEPT
Summary: Beta-catenin is a component of the epithelial apical junction complex via the cadherin-catenin adhesion system.
Reason: Core epithelial junction localization; IDA.
Supporting Evidence:
PMID:16249236
Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network.
GO:0043296 apical junction complex
IDA
PMID:17130295
Distinct subdomain organization and molecular composition of... 		ACCEPT
Summary: Beta-catenin is a component of the epithelial apical junction complex via the cadherin-catenin adhesion system.
Reason: Core epithelial junction localization; IDA.
Supporting Evidence:
PMID:17130295
Distinct subdomain organization and molecular composition of a tight junction with adherens junction features.
GO:0043296 apical junction complex
IDA
PMID:17666436
Shroom2, a myosin-VIIa- and actin-binding protein, directly ... 		ACCEPT
Summary: Beta-catenin is a component of the epithelial apical junction complex via the cadherin-catenin adhesion system.
Reason: Core epithelial junction localization; IDA.
Supporting Evidence:
PMID:17666436
Shroom2, a myosin-VIIa- and actin-binding protein, directly interacts with ZO-1 at tight junctions.
GO:0045177 apical part of cell
IDA
PMID:14758363
The hyh mutation uncovers roles for alpha Snap in apical pro... 		ACCEPT
Summary: Beta-catenin localizes apically in polarized epithelia where adherens junctions concentrate near the apical pole.
Reason: Genuine epithelial pool; IDA-supported.
Supporting Evidence:
PMID:14758363
The hyh mutation uncovers roles for alpha Snap in apical protein localization and control of neural cell fate.
GO:0045177 apical part of cell
IDA
PMID:15037549
Loss of cell polarity causes severe brain dysplasia in Lgl1 ... 		ACCEPT
Summary: Beta-catenin localizes apically in polarized epithelia where adherens junctions concentrate near the apical pole.
Reason: Genuine epithelial pool; IDA-supported.
Supporting Evidence:
PMID:15037549
Loss of cell polarity causes severe brain dysplasia in Lgl1 knockout mice.
GO:0045177 apical part of cell
IDA
PMID:16249236
Shroom regulates epithelial cell shape via the apical positi... 		ACCEPT
Summary: Beta-catenin localizes apically in polarized epithelia where adherens junctions concentrate near the apical pole.
Reason: Genuine epithelial pool; IDA-supported.
Supporting Evidence:
PMID:16249236
Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network.
GO:0045177 apical part of cell
IDA
PMID:23863479
Tumor suppressor Nf2 limits expansion of the neural progenit... 		ACCEPT
Summary: Beta-catenin localizes apically in polarized epithelia where adherens junctions concentrate near the apical pole.
Reason: Genuine epithelial pool; IDA-supported.
Supporting Evidence:
PMID:23863479
Tumor suppressor Nf2 limits expansion of the neural progenitor pool by inhibiting Yap/Taz transcriptional coactivators.
GO:0045294 alpha-catenin binding
IDA
PMID:12432063
Protein kinase CKII regulates the interaction of beta-cateni... 		ACCEPT
Summary: Beta-catenin binds alpha-catenin via its N-terminal region, the key linkage coupling the cadherin-catenin complex to the actin cytoskeleton.
Reason: Core structural MF; crystallographically defined, IPI/IDA.
Supporting Evidence:
PMID:12432063
Protein kinase CKII regulates the interaction of beta-catenin with alpha-catenin and its protein stability.
GO:0045296 cadherin binding
ISO
PMID:10330403
Domains of axin involved in protein-protein interactions, Wn... 		ACCEPT
Summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
Reason: Core structural MF; crystallographically defined, IPI/IBA.
Supporting Evidence:
PMID:10330403
Domains of axin involved in protein-protein interactions, Wnt pathway inhibition, and intracellular localization.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0045296 cadherin binding
IPI
PMID:15023525
Ksp-cadherin is a functional cell-cell adhesion molecule rel... 		ACCEPT
Summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
Reason: Core structural MF; crystallographically defined, IPI/IBA.
Supporting Evidence:
PMID:15023525
Ksp-cadherin is a functional cell-cell adhesion molecule related to LI-cadherin.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0045296 cadherin binding
IPI
PMID:15057752
Beta-catenin is temporally regulated during normal liver dev... 		ACCEPT
Summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
Reason: Core structural MF; crystallographically defined, IPI/IBA.
Supporting Evidence:
PMID:15057752
Beta-catenin is temporally regulated during normal liver development.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0045296 cadherin binding
IPI
PMID:8853988
Expression and cell membrane localization of catenins during... 		ACCEPT
Summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
Reason: Core structural MF; crystallographically defined, IPI/IBA.
Supporting Evidence:
PMID:8853988
Expression and cell membrane localization of catenins during mouse preimplantation development.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
IDA
PMID:16678101
Homeodomain-mediated beta-catenin-dependent switching events... 		ACCEPT
Summary: Beta-catenin directly binds Pol II-specific DNA-binding transcription factors (TCF/LEF) to drive Wnt-responsive transcription.
Reason: Core Wnt coactivation; IDA-supported specific TF binding.
Supporting Evidence:
PMID:16678101
Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
IDA
PMID:22665494
mrhl RNA, a long noncoding RNA, negatively regulates Wnt sig... 		ACCEPT
Summary: Beta-catenin directly binds Pol II-specific DNA-binding transcription factors (TCF/LEF) to drive Wnt-responsive transcription.
Reason: Core Wnt coactivation; IDA-supported specific TF binding.
Supporting Evidence:
PMID:22665494
mrhl RNA, a long noncoding RNA, negatively regulates Wnt signaling through its protein partner Ddx5/p68 in mouse spermatogonial cells.
GO:0140677 molecular function activator activity
EXP
PMID:21075118
Biochemical and structural characterization of Ξ²-catenin int... 		ACCEPT
Summary: Beta-catenin's nuclear role is to act as a transcriptional coactivator (activator) for TCF/LEF factors; this captures its direct molecular-activator function in the Wnt output.
Reason: Direct: as a TCF/LEF coactivator it activates a partner's molecular function, a genuine core MF of beta-catenin.
Supporting Evidence:
PMID:21075118
Biochemical and structural characterization of Ξ²-catenin interactions with nonphosphorylated and CK2-phosphorylated Lef-1.
GO:0021854 hypothalamus development
IMP
PMID:32868762
The cellular and molecular landscape of hypothalamic pattern... 		KEEP AS NON CORE
Summary: Beta-catenin supports hypothalamic neuronal specification via Wnt-driven transcription; a CNS developmental outcome downstream of signaling.
Reason: downstream Wnt-driven hypothalamus development
Supporting Evidence:
PMID:32868762
The cellular and molecular landscape of hypothalamic patterning and differentiation from embryonic to late postnatal development.
GO:0060070 canonical Wnt signaling pathway
IMP
PMID:32868762
The cellular and molecular landscape of hypothalamic pattern... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:32868762
The cellular and molecular landscape of hypothalamic patterning and differentiation from embryonic to late postnatal development.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005886 plasma membrane
TAS
Reactome:R-MMU-9773219 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
GO:0005886 plasma membrane
TAS
Reactome:R-MMU-9860515 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
GO:0005886 plasma membrane
TAS
Reactome:R-MMU-9860560 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
GO:0005886 plasma membrane
TAS
Reactome:R-MMU-9860569 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
GO:0005886 plasma membrane
TAS
Reactome:R-MMU-9863577 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
GO:0005886 plasma membrane
TAS
Reactome:R-NUL-9761463 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
GO:0005634 nucleus
IDA
PMID:30389919
ARTS mediates apoptosis and regeneration of the intestinal s... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:30389919
ARTS mediates apoptosis and regeneration of the intestinal stem cell niche.
GO:0005737 cytoplasm
IDA
PMID:30389919
ARTS mediates apoptosis and regeneration of the intestinal s... 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:30389919
ARTS mediates apoptosis and regeneration of the intestinal stem cell niche.
GO:0005654 nucleoplasm
TAS
Reactome:R-MMU-9735211 		ACCEPT
Summary: Stabilized beta-catenin accumulates in the nucleoplasm to act as the Wnt transcriptional coactivator.
Reason: Genuine nuclear pool; TAS.
GO:0005654 nucleoplasm
TAS
Reactome:R-MMU-9754284 		ACCEPT
Summary: Stabilized beta-catenin accumulates in the nucleoplasm to act as the Wnt transcriptional coactivator.
Reason: Genuine nuclear pool; TAS.
GO:0005654 nucleoplasm
TAS
Reactome:R-MMU-9793864 		ACCEPT
Summary: Stabilized beta-catenin accumulates in the nucleoplasm to act as the Wnt transcriptional coactivator.
Reason: Genuine nuclear pool; TAS.
GO:0005654 nucleoplasm
TAS
Reactome:R-MMU-9794042 		ACCEPT
Summary: Stabilized beta-catenin accumulates in the nucleoplasm to act as the Wnt transcriptional coactivator.
Reason: Genuine nuclear pool; TAS.
GO:0005654 nucleoplasm
TAS
Reactome:R-MMU-9823738 		ACCEPT
Summary: Stabilized beta-catenin accumulates in the nucleoplasm to act as the Wnt transcriptional coactivator.
Reason: Genuine nuclear pool; TAS.
GO:0005654 nucleoplasm
TAS
Reactome:R-MMU-9824206 		ACCEPT
Summary: Stabilized beta-catenin accumulates in the nucleoplasm to act as the Wnt transcriptional coactivator.
Reason: Genuine nuclear pool; TAS.
GO:0005654 nucleoplasm
TAS
Reactome:R-MMU-9824277 		ACCEPT
Summary: Stabilized beta-catenin accumulates in the nucleoplasm to act as the Wnt transcriptional coactivator.
Reason: Genuine nuclear pool; TAS.
GO:0005654 nucleoplasm
TAS
Reactome:R-MMU-9824278 		ACCEPT
Summary: Stabilized beta-catenin accumulates in the nucleoplasm to act as the Wnt transcriptional coactivator.
Reason: Genuine nuclear pool; TAS.
GO:0140297 DNA-binding transcription factor binding
IPI
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells a... 		ACCEPT
Summary: Beta-catenin binds TCF/LEF DNA-binding transcription factors to coactivate Wnt target genes; core to its nuclear Wnt-effector role.
Reason: Core Wnt: direct TCF/LEF coactivation (IPI); foundational MF for the transcriptional arm.
Supporting Evidence:
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
GO:0005912 adherens junction
IDA
PMID:20399730
The apical complex couples cell fate and cell survival to ce... 		ACCEPT
Summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
Reason: Core structural localization; strongly supported (IBA/IDA).
Supporting Evidence:
PMID:20399730
The apical complex couples cell fate and cell survival to cerebral cortical development.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005886 plasma membrane
IDA
PMID:17920587
FERM protein EPB41L5 is a novel member of the mammalian CRB-... 		ACCEPT
Summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
Reason: Core localization; IDA/TAS-supported.
Supporting Evidence:
PMID:17920587
FERM protein EPB41L5 is a novel member of the mammalian CRB-MPP5 polarity complex.
GO:1990907 beta-catenin-TCF complex
IDA
PMID:20371816
LEF1/beta-catenin complex regulates transcription of the Cav... 		ACCEPT
Summary: The nuclear beta-catenin-TCF complex is the central transcriptional effector unit of canonical Wnt signaling.
Reason: Core Wnt effector complex; IDA-supported.
Supporting Evidence:
PMID:20371816
LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1g) in thalamic neurons of the adult brain.
GO:0032968 positive regulation of transcription elongation by RNA polymerase II
IMP
PMID:30478225
TBX2 and TBX3 act downstream of canonical WNT signaling in p... 		KEEP AS NON CORE
Summary: IMP annotation; beta-catenin can promote elongation (e.g. via TNIK/PAF1c at Wnt targets), a specific mechanistic facet that is secondary to its core coactivator recruitment role.
Reason: Specific mechanistic facet; experimental, downgrade not remove.
Supporting Evidence:
PMID:30478225
TBX2 and TBX3 act downstream of canonical WNT signaling in patterning and differentiation of the mouse ureteric mesenchyme.
GO:0060070 canonical Wnt signaling pathway
IMP
PMID:30478225
TBX2 and TBX3 act downstream of canonical WNT signaling in p... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:30478225
TBX2 and TBX3 act downstream of canonical WNT signaling in patterning and differentiation of the mouse ureteric mesenchyme.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005515 protein binding
IPI
PMID:15110721
Sox1 acts through multiple independent pathways to promote n... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:15110721
Sox1 acts through multiple independent pathways to promote neurogenesis.
GO:0045944 positive regulation of transcription by RNA polymerase II
IMP
PMID:15110721
Sox1 acts through multiple independent pathways to promote n... 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
Supporting Evidence:
PMID:15110721
Sox1 acts through multiple independent pathways to promote neurogenesis.
GO:0005515 protein binding
IPI
PMID:31073040
LMBR1L regulates lymphopoiesis through Wnt/Ξ²-catenin signali... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:31073040
LMBR1L regulates lymphopoiesis through Wnt/Ξ²-catenin signaling.
GO:0005911 cell-cell junction
IDA
PMID:24338362
POPX2 phosphatase regulates the KIF3 kinesin motor complex. 		ACCEPT
Summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
Reason: Core junctional localization; IDA.
Supporting Evidence:
PMID:24338362
POPX2 phosphatase regulates the KIF3 kinesin motor complex.
GO:0060070 canonical Wnt signaling pathway
IDA
PMID:15314168
Cyclin D1 genetic heterozygosity regulates colonic epithelia... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:15314168
Cyclin D1 genetic heterozygosity regulates colonic epithelial cell differentiation and tumor number in ApcMin mice.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0003713 transcription coactivator activity
IMP
PMID:26371318
Lhx2 regulates the timing of Ξ²-catenin-dependent cortical ne... 		ACCEPT
Summary: The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.
Reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
Supporting Evidence:
PMID:26371318
Lhx2 regulates the timing of Ξ²-catenin-dependent cortical neurogenesis.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0005634 nucleus
IMP
PMID:26371318
Lhx2 regulates the timing of Ξ²-catenin-dependent cortical ne... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:26371318
Lhx2 regulates the timing of Ξ²-catenin-dependent cortical neurogenesis.
GO:0045944 positive regulation of transcription by RNA polymerase II
IMP
PMID:26371318
Lhx2 regulates the timing of Ξ²-catenin-dependent cortical ne... 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
Supporting Evidence:
PMID:26371318
Lhx2 regulates the timing of Ξ²-catenin-dependent cortical neurogenesis.
GO:0050768 negative regulation of neurogenesis
IMP
PMID:26371318
Lhx2 regulates the timing of Ξ²-catenin-dependent cortical ne... 		KEEP AS NON CORE
Summary: Beta-catenin can suppress neuronal differentiation by maintaining neural progenitors (Wnt stemness targets); a downstream CNS-development phenotype.
Reason: Neurogenesis suppression downstream of Wnt progenitor-maintenance transcription.
Supporting Evidence:
PMID:26371318
Lhx2 regulates the timing of Ξ²-catenin-dependent cortical neurogenesis.
GO:2000179 positive regulation of neural precursor cell proliferation
IMP
PMID:26371318
Lhx2 regulates the timing of Ξ²-catenin-dependent cortical ne... 		KEEP AS NON CORE
Summary: Beta-catenin enlarges the neural precursor pool by activating Wnt cell-cycle genes; a downstream CNS-development phenotype.
Reason: Neural-precursor expansion downstream of Wnt mitogenic targets.
Supporting Evidence:
PMID:26371318
Lhx2 regulates the timing of Ξ²-catenin-dependent cortical neurogenesis.
GO:0003682 chromatin binding
IDA
PMID:20371816
LEF1/beta-catenin complex regulates transcription of the Cav... 		ACCEPT
Summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
Reason: Core nuclear Wnt role; IDA/IGI-supported.
Supporting Evidence:
PMID:20371816
LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1g) in thalamic neurons of the adult brain.
GO:1990907 beta-catenin-TCF complex
IDA
PMID:9488439
Two members of the Tcf family implicated in Wnt/beta-catenin... 		ACCEPT
Summary: The nuclear beta-catenin-TCF complex is the central transcriptional effector unit of canonical Wnt signaling.
Reason: Core Wnt effector complex; IDA-supported.
Supporting Evidence:
PMID:9488439
Two members of the Tcf family implicated in Wnt/beta-catenin signaling during embryogenesis in the mouse.
GO:1990138 neuron projection extension
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Ortholog/electronic-inferred role in axon/dendrite outgrowth, plausibly via cadherin-junction and Wnt-transcriptional inputs; a downstream neuronal phenotype.
Reason: Neurite extension downstream of adhesion/Wnt roles; non-core (electronic).
GO:0005515 protein binding
IPI
PMID:25232112
Dlg5 regulates dendritic spine formation and synaptogenesis ... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:25232112
Dlg5 regulates dendritic spine formation and synaptogenesis by controlling subcellular N-cadherin localization.
GO:0045202 synapse
IDA
PMID:25232112
Dlg5 regulates dendritic spine formation and synaptogenesis ... 		KEEP AS NON CORE
Summary: Synaptic localization supports cadherin-based synaptic adhesion in neurons, a tissue-specific pool.
Reason: Synapse localization; IDA/IEA, non-core.
Supporting Evidence:
PMID:25232112
Dlg5 regulates dendritic spine formation and synaptogenesis by controlling subcellular N-cadherin localization.
GO:0016525 negative regulation of angiogenesis
IMP
PMID:25961718
Resveratrol-Induced Vascular Progenitor Differentiation towa... 		KEEP AS NON CORE
Summary: Endothelial Wnt/beta-catenin signaling can restrain vessel sprouting through transcriptional targets; a context-dependent downstream vascular phenotype.
Reason: Angiogenesis regulation downstream of endothelial Wnt-transcriptional output.
Supporting Evidence:
PMID:25961718
Resveratrol-Induced Vascular Progenitor Differentiation towards Endothelial Lineage via MiR-21/Akt/Ξ²-Catenin Is Protective in Vessel Graft Models.
GO:0005634 nucleus
IDA
PMID:24681597
Kindlin-1 controls Wnt and TGF-Ξ² availability to regulate cu... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:24681597
Kindlin-1 controls Wnt and TGF-Ξ² availability to regulate cutaneous stem cell proliferation.
GO:0005737 cytoplasm
IDA
PMID:24681597
Kindlin-1 controls Wnt and TGF-Ξ² availability to regulate cu... 		ACCEPT
Summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
Reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:24681597
Kindlin-1 controls Wnt and TGF-Ξ² availability to regulate cutaneous stem cell proliferation.
GO:0051884 regulation of timing of anagen
IDA
PMID:24681597
Kindlin-1 controls Wnt and TGF-Ξ² availability to regulate cu... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt activity initiates the hair-follicle growth (anagen) phase; an IDA developmental-timing phenotype downstream of transcription.
Reason: Hair-cycle anagen timing downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:24681597
Kindlin-1 controls Wnt and TGF-Ξ² availability to regulate cutaneous stem cell proliferation.
GO:0060070 canonical Wnt signaling pathway
IDA
PMID:24681597
Kindlin-1 controls Wnt and TGF-Ξ² availability to regulate cu... 		ACCEPT
Summary: The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).
Reason: Central, multiply-supported core function of the gene.
Supporting Evidence:
PMID:24681597
Kindlin-1 controls Wnt and TGF-Ξ² availability to regulate cutaneous stem cell proliferation.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0016342 catenin complex
IMP
PMID:11121423
The cadherin cytoplasmic domain is unstructured in the absen... 		ACCEPT
Summary: Beta-catenin is a defining member of the catenin (cadherin-catenin) complex linking cadherins to alpha-catenin/actin.
Reason: Core complex; broadly supported (IBA/IDA/IMP/ISS).
Supporting Evidence:
PMID:11121423
The cadherin cytoplasmic domain is unstructured in the absence of beta-catenin. A possible mechanism for regulating cadherin turnover.
GO:0045296 cadherin binding
IPI
PMID:11121423
The cadherin cytoplasmic domain is unstructured in the absen... 		ACCEPT
Summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
Reason: Core structural MF; crystallographically defined, IPI/IBA.
Supporting Evidence:
PMID:11121423
The cadherin cytoplasmic domain is unstructured in the absence of beta-catenin. A possible mechanism for regulating cadherin turnover.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0097718 disordered domain specific binding
IPI
PMID:11121423
The cadherin cytoplasmic domain is unstructured in the absen... 		KEEP AS NON CORE
Summary: Binding to intrinsically disordered regions of partners (e.g. cadherin/APC tails) is a real biophysical mode but a generic descriptor of specific interactions captured elsewhere.
Reason: Generic-ish MF; IPI but peripheral to named partner terms.
Supporting Evidence:
PMID:11121423
The cadherin cytoplasmic domain is unstructured in the absence of beta-catenin. A possible mechanism for regulating cadherin turnover.
GO:0005634 nucleus
IDA
PMID:20371816
LEF1/beta-catenin complex regulates transcription of the Cav... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:20371816
LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1g) in thalamic neurons of the adult brain.
GO:0005829 cytosol
IDA
PMID:20371816
LEF1/beta-catenin complex regulates transcription of the Cav... 		ACCEPT
Summary: Beta-catenin has a cytosolic pool subject to destruction-complex regulation and Wnt-dependent stabilization.
Reason: Genuine pool; IDA/TAS-supported.
Supporting Evidence:
PMID:20371816
LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1g) in thalamic neurons of the adult brain.
GO:0016020 membrane
IDA
PMID:20371816
LEF1/beta-catenin complex regulates transcription of the Cav... 		KEEP AS NON CORE
Summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
Reason: Over-general CC parent.
Supporting Evidence:
PMID:20371816
LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1g) in thalamic neurons of the adult brain.
GO:0045944 positive regulation of transcription by RNA polymerase II
IGI
PMID:20371816
LEF1/beta-catenin complex regulates transcription of the Cav... 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
Supporting Evidence:
PMID:20371816
LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1g) in thalamic neurons of the adult brain.
GO:0005634 nucleus
IDA
PMID:25979161
Transmembrane protein 64 reciprocally regulates osteoblast a... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:25979161
Transmembrane protein 64 reciprocally regulates osteoblast and adipocyte differentiation by modulating Wnt/Ξ²-catenin signaling.
GO:1904948 midbrain dopaminergic neuron differentiation
IMP
PMID:19122665
Wnt antagonism of Shh facilitates midbrain floor plate neuro... 		KEEP AS NON CORE
Summary: Beta-catenin drives midbrain dopaminergic neuron differentiation via Wnt1/TCF transcription; a neuronal cell-fate outcome downstream of signaling.
Reason: downstream Wnt-driven midbrain DA neuron fate
Supporting Evidence:
PMID:19122665
Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis.
GO:0005634 nucleus
IDA
PMID:22645310
Prolyl isomerase Pin1 regulates neuronal differentiation via... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:22645310
Prolyl isomerase Pin1 regulates neuronal differentiation via Ξ²-catenin.
GO:0005829 cytosol
IDA
PMID:22645310
Prolyl isomerase Pin1 regulates neuronal differentiation via... 		ACCEPT
Summary: Beta-catenin has a cytosolic pool subject to destruction-complex regulation and Wnt-dependent stabilization.
Reason: Genuine pool; IDA/TAS-supported.
Supporting Evidence:
PMID:22645310
Prolyl isomerase Pin1 regulates neuronal differentiation via Ξ²-catenin.
GO:0019899 enzyme binding
IPI
PMID:22645310
Prolyl isomerase Pin1 regulates neuronal differentiation via... 		MARK AS OVER ANNOTATED
Summary: Bare 'enzyme binding' is uninformative; beta-catenin's relevant enzyme contacts (GSK3B, CK1, kinases) are captured by specific kinase/phosphatase terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:22645310
Prolyl isomerase Pin1 regulates neuronal differentiation via Ξ²-catenin.
GO:1904888 cranial skeletal system development
IMP
PMID:11262227
Inactivation of the beta-catenin gene by Wnt1-Cre-mediated d... 		KEEP AS NON CORE
Summary: Beta-catenin patterns craniofacial skeleton via Wnt-driven osteochondral fate decisions; a skeletal developmental outcome, not core function.
Reason: downstream Wnt-driven craniofacial skeletogenesis
Supporting Evidence:
PMID:11262227
Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
GO:0030901 midbrain development
IMP
PMID:11262227
Inactivation of the beta-catenin gene by Wnt1-Cre-mediated d... 		KEEP AS NON CORE
Summary: Beta-catenin patterns midbrain via Wnt/TCF transcription and progenitor control; a CNS developmental outcome, not core function.
Reason: downstream Wnt-driven midbrain development
Supporting Evidence:
PMID:11262227
Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
GO:0030902 hindbrain development
IMP
PMID:11262227
Inactivation of the beta-catenin gene by Wnt1-Cre-mediated d... 		KEEP AS NON CORE
Summary: Beta-catenin patterns hindbrain via Wnt/TCF transcription and progenitor control; a CNS developmental outcome, not core function.
Reason: downstream Wnt-driven hindbrain development
Supporting Evidence:
PMID:11262227
Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
GO:0061550 cranial ganglion development
IMP
PMID:11262227
Inactivation of the beta-catenin gene by Wnt1-Cre-mediated d... 		KEEP AS NON CORE
Summary: Beta-catenin supports cranial ganglion/placode development through Wnt/TCF transcription; a neural-crest/placode outcome downstream of signaling.
Reason: downstream Wnt role in cranial ganglion development
Supporting Evidence:
PMID:11262227
Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
GO:1990403 embryonic brain development
IMP
PMID:11262227
Inactivation of the beta-catenin gene by Wnt1-Cre-mediated d... 		KEEP AS NON CORE
Summary: Beta-catenin supports embryonic brain growth/patterning via Wnt/TCF neural transcription; a CNS developmental outcome, not core function.
Reason: downstream Wnt-driven embryonic brain development
Supporting Evidence:
PMID:11262227
Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
GO:1990791 dorsal root ganglion development
IMP
PMID:11262227
Inactivation of the beta-catenin gene by Wnt1-Cre-mediated d... 		KEEP AS NON CORE
Summary: Beta-catenin supports DRG formation from neural crest via Wnt/TCF transcription; a peripheral-nervous-system developmental outcome, not core function.
Reason: downstream Wnt-driven DRG development
Supporting Evidence:
PMID:11262227
Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
GO:1990909 Wnt signalosome
IDA
PMID:22899650
LRRK2 functions as a Wnt signaling scaffold, bridging cytoso... 		ACCEPT
Summary: IDA-supported: stabilized beta-catenin is a component of the Wnt signalosome where it escapes destruction-complex phosphorylation. Core to its Wnt-effector role.
Reason: Experimental component annotation central to canonical Wnt signaling.
Supporting Evidence:
PMID:22899650
LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6.
GO:0019901 protein kinase binding
IPI
PMID:22899650
LRRK2 functions as a Wnt signaling scaffold, bridging cytoso... 		KEEP AS NON CORE
Summary: Protein-kinase binding reflects regulatory contacts (GSK3B, CK1, CDKs) governing beta-catenin stability; specific destruction-complex terms are more informative.
Reason: Semi-generic regulatory MF; IPI, non-core.
Supporting Evidence:
PMID:22899650
LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6.
GO:0005515 protein binding
IPI
PMID:15908431
MAGI1 recruits Dll1 to cadherin-based adherens junctions and... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:15908431
MAGI1 recruits Dll1 to cadherin-based adherens junctions and stabilizes it on the cell surface.
GO:0010629 negative regulation of gene expression
IMP
PMID:19122665
Wnt antagonism of Shh facilitates midbrain floor plate neuro... 		MARK AS OVER ANNOTATED
Summary: Generic negative-regulation-of-expression parent; beta-catenin's specific repressive effects act at the level of Pol II transcription of particular targets.
Reason: Uninformative broad parent; specific Pol II transcription terms preferred.
Supporting Evidence:
PMID:19122665
Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis.
GO:0030182 neuron differentiation
IMP
PMID:25009587
Depletion of canonical Wnt signaling components has a neurop... 		KEEP AS NON CORE
Summary: Beta-catenin influences neuronal differentiation timing via Wnt-target transcription; a downstream neurodevelopmental process.
Reason: Neuronal differentiation downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:25009587
Depletion of canonical Wnt signaling components has a neuroprotective effect on midbrain dopaminergic neurons in an MPTP-induced mouse model of Parkinson's disease.
GO:0016600 flotillin complex
IDA
PMID:24046456
Flotillin microdomains stabilize cadherins at cell-cell junc... 		KEEP AS NON CORE
Summary: A reported flotillin-complex association reflects a membrane microdomain pool, peripheral to beta-catenin's core junction/Wnt functions.
Reason: Specialized complex; IDA but non-core.
Supporting Evidence:
PMID:24046456
Flotillin microdomains stabilize cadherins at cell-cell junctions.
GO:0000791 euchromatin
IDA
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells a... 		KEEP AS NON CORE
Summary: beta-catenin localizes with active TCF/LEF target loci in euchromatin, consistent with its coactivator role, but this CC term is contextual rather than a core function statement.
Reason: Localization term supporting, but not equal to, its coactivator function.
Supporting Evidence:
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
GO:0005667 transcription regulator complex
IDA
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells a... 		ACCEPT
Summary: Beta-catenin is a component of transcription regulator complexes (with TCF/LEF and coactivators) that drive Wnt target gene expression.
Reason: Core nuclear Wnt effector complex; IDA-supported.
Supporting Evidence:
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
GO:0002052 positive regulation of neuroblast proliferation
IMP
PMID:21325504
Frizzled3 is required for neurogenesis and target innervatio... 		KEEP AS NON CORE
Summary: Beta-catenin positively drives neuroblast expansion through Wnt cell-cycle targets; a downstream neurodevelopmental proliferative role.
Reason: Pro-neuroblast proliferation downstream of Wnt transcription.
Supporting Evidence:
PMID:21325504
Frizzled3 is required for neurogenesis and target innervation during sympathetic nervous system development.
GO:0045976 negative regulation of mitotic cell cycle, embryonic
IMP
PMID:21325504
Frizzled3 is required for neurogenesis and target innervatio... 		KEEP AS NON CORE
Summary: Beta-catenin restrains embryonic mitotic cycling in specific contexts via Wnt cell-cycle target genes; a downstream developmental phenotype.
Reason: Embryonic cell-cycle restraint downstream of Wnt transcription.
Supporting Evidence:
PMID:21325504
Frizzled3 is required for neurogenesis and target innervation during sympathetic nervous system development.
GO:0061549 sympathetic ganglion development
IMP
PMID:21325504
Frizzled3 is required for neurogenesis and target innervatio... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling supports sympathetic neuron lineage development; a downstream peripheral-nervous-system phenotype.
Reason: Sympathetic ganglion development downstream of Wnt transcription.
Supporting Evidence:
PMID:21325504
Frizzled3 is required for neurogenesis and target innervation during sympathetic nervous system development.
GO:0005515 protein binding
IPI
PMID:23856522
Jmjd3 controls mesodermal and cardiovascular differentiation... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:23856522
Jmjd3 controls mesodermal and cardiovascular differentiation of embryonic stem cells.
GO:0005634 nucleus
IDA
PMID:23856522
Jmjd3 controls mesodermal and cardiovascular differentiation... 		ACCEPT
Summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
Reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
Supporting Evidence:
PMID:23856522
Jmjd3 controls mesodermal and cardiovascular differentiation of embryonic stem cells.
GO:0016922 nuclear receptor binding
IPI
PMID:14687547
RORalpha coordinates reciprocal signaling in cerebellar deve... 		KEEP AS NON CORE
Summary: Beta-catenin coactivates several nuclear receptors (e.g. NR5A2, AR/ER), broadening its transcriptional crosstalk beyond the core TCF/LEF axis.
Reason: Crosstalk coactivation; non-core relative to TCF.
Supporting Evidence:
PMID:14687547
RORalpha coordinates reciprocal signaling in cerebellar development through sonic hedgehog and calcium-dependent pathways.
GO:0033234 negative regulation of protein sumoylation
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Ortholog/electronic-inferred negative effect on SUMOylation; an indirect downstream activity unrelated to beta-catenin's core adhesion/Wnt functions.
Reason: SUMOylation suppression, electronic-inferred and indirect; non-core.
GO:0048643 positive regulation of skeletal muscle tissue development
IMP
PMID:23460868
Ξ²-catenin is essential for efficient in vitro premyogenic me... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling supports skeletal muscle tissue formation by driving myogenic gene programs; a downstream tissue-development role.
Reason: Skeletal muscle development downstream of Wnt/beta-catenin transcription.
Supporting Evidence:
PMID:23460868
Ξ²-catenin is essential for efficient in vitro premyogenic mesoderm formation but can be partially compensated by retinoic acid signalling.
GO:0005515 protein binding
IPI
PMID:11590244
alphaT-catenin: a novel tissue-specific beta-catenin-binding... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:11590244
alphaT-catenin: a novel tissue-specific beta-catenin-binding protein mediating strong cell-cell adhesion.
GO:0036023 embryonic skeletal limb joint morphogenesis
IGI
PMID:21262216
The zinc finger transcription factors Osr1 and Osr2 control ... 		KEEP AS NON CORE
Summary: Beta-catenin specifies limb joint interzones via Wnt/TCF transcription (IGI); a skeletal morphogenetic outcome downstream of its signaling role.
Reason: downstream Wnt-driven limb joint morphogenesis
Supporting Evidence:
PMID:21262216
The zinc finger transcription factors Osr1 and Osr2 control synovial joint formation.
GO:0045294 alpha-catenin binding
IPI
PMID:21393547
A polarized epithelium organized by beta- and alpha-catenin ... 		ACCEPT
Summary: Beta-catenin binds alpha-catenin via its N-terminal region, the key linkage coupling the cadherin-catenin complex to the actin cytoskeleton.
Reason: Core structural MF; crystallographically defined, IPI/IDA.
Supporting Evidence:
PMID:21393547
A polarized epithelium organized by beta- and alpha-catenin predates cadherin and metazoan origins.
GO:0005515 protein binding
IPI
PMID:18636119
Coxsackievirus and adenovirus receptor (CAR) mediates atriov... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:18636119
Coxsackievirus and adenovirus receptor (CAR) mediates atrioventricular-node function and connexin 45 localization in the murine heart.
GO:0072182 regulation of nephron tubule epithelial cell differentiation
IMP
PMID:19112489
Gata3 acts downstream of beta-catenin signaling to prevent e... 		KEEP AS NON CORE
Summary: Beta-catenin tunes nephron epithelial cell fate during kidney development via Wnt targets; a downstream renal phenotype.
Reason: Nephron epithelial differentiation control downstream of Wnt transcription.
Supporting Evidence:
PMID:19112489
Gata3 acts downstream of beta-catenin signaling to prevent ectopic metanephric kidney induction.
GO:0045893 positive regulation of DNA-templated transcription
IMP
PMID:19112489
Gata3 acts downstream of beta-catenin signaling to prevent e... 		MODIFY
Summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
Reason: Generic parent; specialize to Pol II-specific positive regulation.
Supporting Evidence:
PMID:19112489
Gata3 acts downstream of beta-catenin signaling to prevent ectopic metanephric kidney induction.
GO:0071944 cell periphery
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Beta-catenin localizes to the cell periphery at adherens junctions linking cadherins to actin; a broad location term consistent with its structural role but less specific than the junction terms.
Reason: electronic broad location subsumed by adherens-junction terms
GO:0005938 cell cortex
ISS
GO_REF:0000024 		ACCEPT
Summary: Beta-catenin associates with the actin-rich cell cortex via the cadherin-catenin complex at cell-cell contacts.
Reason: Genuine cortical pool at junctions.
GO:0007155 cell adhesion
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Generic cell adhesion is subsumed by the more specific cadherin-mediated cell-cell adhesion terms that capture beta-catenin's actual mechanism.
Reason: Over-general parent; electronic; specific child preferred.
GO:0008285 negative regulation of cell population proliferation
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Electronic/ortholog-inferred anti-proliferative effect in some lineages, downstream of context-specific Wnt transcriptional output.
Reason: Context anti-proliferation downstream of transcription; non-core (electronic).
GO:0010909 positive regulation of heparan sulfate proteoglycan biosynthetic process
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Ortholog/electronic-inferred up-regulation of HSPG biosynthesis, plausibly via Wnt transcriptional targets; a downstream biosynthetic effect.
Reason: HSPG biosynthesis upregulation downstream of transcription; non-core (electronic).
GO:0016342 catenin complex
ISS
GO_REF:0000024 		ACCEPT
Summary: Beta-catenin is a defining member of the catenin (cadherin-catenin) complex linking cadherins to alpha-catenin/actin.
Reason: Core complex; broadly supported (IBA/IDA/IMP/ISS).
GO:0030054 cell junction
ISS
GO_REF:0000024 		ACCEPT
Summary: Beta-catenin is a core cell-junction protein, concentrated at cadherin-based cell-cell junctions.
Reason: Core localization (junction parent).
GO:0030877 beta-catenin destruction complex
ISS
GO_REF:0000024 		ACCEPT
Summary: In the absence of Wnt, beta-catenin is the substrate within the AXIN/APC/GSK3B/CK1 destruction complex that drives its phosphorylation and degradation.
Reason: Core Wnt regulation; defining complex membership (IDA/ISS).
GO:0030997 regulation of centriole-centriole cohesion
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Beta-catenin has a reported centrosomal moonlighting role in centriole cohesion; ortholog/electronic-inferred and distinct from its core adhesion/Wnt roles.
Reason: Centrosomal moonlighting role, electronic-inferred; non-core.
GO:0032355 response to estradiol
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Ortholog/electronic-inferred responsiveness to estradiol, reflecting hormone crosstalk with Wnt/beta-catenin transcription in reproductive tissues; a downstream response.
Reason: Estradiol response downstream/crosstalk with Wnt transcription; non-core (electronic).
GO:0032993 protein-DNA complex
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Beta-catenin is part of protein-DNA complexes only indirectly via TCF/LEF; the specific beta-catenin-TCF complex terms capture this better.
Reason: Indirect/over-general; electronic.
GO:0034333 adherens junction assembly
ISS
GO_REF:0000024 		ACCEPT
Summary: By linking cadherin to the catenin/actin machinery, beta-catenin is required for adherens junction assembly.
Reason: Core adhesion process; mechanistically central even if evidence is electronic/ISS.
GO:0034394 protein localization to cell surface
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Beta-catenin promotes surface delivery/retention of cadherin (e.g. via vinculin), a supporting trafficking role secondary to its structural function.
Reason: Peripheral process; electronic.
GO:0043065 positive regulation of apoptotic process
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: In some contexts beta-catenin promotes apoptosis; this electronic/ortholog-inferred bidirectional effect is a downstream consequence of context-specific transcription.
Reason: Context-dependent pro-apoptotic output downstream of transcription; non-core (electronic).
GO:0045944 positive regulation of transcription by RNA polymerase II
ISS
GO_REF:0000024 		ACCEPT
Summary: Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.
Reason: Central coactivator function, multiply and experimentally supported.
GO:0048471 perinuclear region of cytoplasm
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: A perinuclear cytoplasmic pool may reflect shuttling/staging intermediates, secondary to functional junctional and nuclear pools.
Reason: Secondary localization; electronic.
GO:0048660 regulation of smooth muscle cell proliferation
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Modulation of vascular/visceral smooth muscle proliferation reflects Wnt/beta-catenin mitogenic target genes; ortholog/electronic-inferred downstream process.
Reason: Downstream proliferative control via Wnt transcriptional targets; non-core.
GO:0061154 endothelial tube morphogenesis
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Beta-catenin supports endothelial tube formation via junctional integrity and Wnt transcription; a vascular morphogenetic outcome (electronic) downstream of its dual role.
Reason: electronic; downstream of junction/Wnt vascular roles
GO:0070369 beta-catenin-TCF7L2 complex
ISS
GO_REF:0000024 		ACCEPT
Summary: Beta-catenin forms the specific transcriptional complex with TCF7L2/TCF4 that activates Wnt target genes.
Reason: Core Wnt effector complex (specific TCF member).
GO:0071363 cellular response to growth factor stimulus
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Beta-catenin participates in growth-factor-responsive transcription via Wnt crosstalk; a broad, electronically inferred response, kept as non-core given indirect linkage.
Reason: electronic/generic; indirect crosstalk, not core
GO:0071681 cellular response to indole-3-methanol
ISS
GO_REF:0000024 		REMOVE
Summary: No credible biological basis for beta-catenin as a responder to indole-3-methanol; an electronically propagated (IEA/ISO/ISS) annotation with no support.
Reason: electronic annotation biologically unsupported for this gene
GO:0090279 regulation of calcium ion import
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Ortholog/electronic-inferred influence on calcium import, distinct from beta-catenin's core Wnt/adhesion roles; a downstream/indirect effect.
Reason: Calcium-import regulation, electronic-inferred and indirect; non-core.
GO:2000008 regulation of protein localization to cell surface
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: Beta-catenin modulates cadherin surface levels, a regulatory trafficking role secondary to its structural junction function.
Reason: Peripheral regulatory process; electronic.
GO:0005515 protein binding
IPI
PMID:20802155
Sox17 modulates Wnt3A/beta-catenin-mediated transcriptional ... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:20802155
Sox17 modulates Wnt3A/beta-catenin-mediated transcriptional activation of the Lef-1 promoter.
GO:0034750 Scrib-APC-beta-catenin complex
IDA
PMID:16611247
Human scribble, a novel tumor suppressor identified as a tar... 		KEEP AS NON CORE
Summary: Beta-catenin participates in a Scrib-APC complex linked to synaptic vesicle localization and polarity, a specialized assembly beyond core adhesion/Wnt complexes.
Reason: Specialized complex (IDA); peripheral, neuronal-polarity context.
Supporting Evidence:
PMID:16611247
Human scribble, a novel tumor suppressor identified as a target of high-risk HPV E6 for ubiquitin-mediated degradation, interacts with adenomatous polyposis coli.
GO:0005813 centrosome
IDA
PMID:20300119
Conductin/axin2 and Wnt signalling regulates centrosome cohe... 		KEEP AS NON CORE
Summary: Beta-catenin has a reported centrosomal pool acting in centrosome cohesion/separation, distinct from its core adhesion and Wnt roles.
Reason: Secondary localization; IDA but non-core moonlighting.
Supporting Evidence:
PMID:20300119
Conductin/axin2 and Wnt signalling regulates centrosome cohesion.
GO:0070602 regulation of centromeric sister chromatid cohesion
IMP
PMID:20300119
Conductin/axin2 and Wnt signalling regulates centrosome cohe... 		KEEP AS NON CORE
Summary: A reported beta-catenin role at centromeric cohesion is a moonlighting function separate from its Wnt/adhesion core; supported by IMP plus electronic inference.
Reason: Sister-chromatid cohesion moonlighting role; non-core to Wnt/adhesion.
Supporting Evidence:
PMID:20300119
Conductin/axin2 and Wnt signalling regulates centrosome cohesion.
GO:0003713 transcription coactivator activity
IDA
PMID:12949260
Wnt4 overexpression disrupts normal testicular vasculature a... 		ACCEPT
Summary: The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.
Reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
Supporting Evidence:
PMID:12949260
Wnt4 overexpression disrupts normal testicular vasculature and inhibits testosterone synthesis by repressing steroidogenic factor 1/beta-catenin synergy.
file:mouse/Ctnnb1/Ctnnb1-deep-research.md
Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
GO:0045893 positive regulation of DNA-templated transcription
IDA
PMID:12949260
Wnt4 overexpression disrupts normal testicular vasculature a... 		MODIFY
Summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
Reason: Generic parent; specialize to Pol II-specific positive regulation.
Supporting Evidence:
PMID:12949260
Wnt4 overexpression disrupts normal testicular vasculature and inhibits testosterone synthesis by repressing steroidogenic factor 1/beta-catenin synergy.
GO:0005515 protein binding
IPI
PMID:20413591
The TRPV4 channel contributes to intercellular junction form... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:20413591
The TRPV4 channel contributes to intercellular junction formation in keratinocytes.
GO:0003223 ventricular compact myocardium morphogenesis
TAS
PMID:20299672
Epicardial-myocardial signaling directing coronary vasculoge... 		KEEP AS NON CORE
Summary: Beta-catenin Wnt signaling contributes to compact-layer ventricular wall formation; a TAS downstream cardiac-morphogenesis phenotype.
Reason: Compact myocardium morphogenesis downstream of Wnt transcription (TAS).
Supporting Evidence:
PMID:20299672
Epicardial-myocardial signaling directing coronary vasculogenesis.
GO:0010718 positive regulation of epithelial to mesenchymal transition
TAS
PMID:20299672
Epicardial-myocardial signaling directing coronary vasculoge... 		KEEP AS NON CORE
Summary: Nuclear beta-catenin drives EMT transcriptional programs (Snail/Twist targets) while loss of its junctional pool also promotes EMT; the process is downstream of both core roles.
Reason: EMT is a transcriptional/adhesion downstream output, not beta-catenin's direct molecular function.
Supporting Evidence:
PMID:20299672
Epicardial-myocardial signaling directing coronary vasculogenesis.
GO:0060038 cardiac muscle cell proliferation
TAS
PMID:20299672
Epicardial-myocardial signaling directing coronary vasculoge... 		KEEP AS NON CORE
Summary: Beta-catenin supports cardiomyocyte proliferation via Wnt/TCF transcription; a cardiac-growth outcome downstream of its signaling effector role (TAS).
Reason: downstream Wnt-driven cardiomyocyte proliferation
Supporting Evidence:
PMID:20299672
Epicardial-myocardial signaling directing coronary vasculogenesis.
GO:0060485 mesenchyme development
TAS
PMID:20299672
Epicardial-myocardial signaling directing coronary vasculoge... 		KEEP AS NON CORE
Summary: Beta-catenin supports mesenchymal tissue development via Wnt-driven transcription; a connective-tissue developmental outcome (TAS) downstream of signaling.
Reason: downstream Wnt-driven mesenchyme development
Supporting Evidence:
PMID:20299672
Epicardial-myocardial signaling directing coronary vasculogenesis.
GO:0060947 cardiac vascular smooth muscle cell differentiation
TAS
PMID:20299672
Epicardial-myocardial signaling directing coronary vasculoge... 		KEEP AS NON CORE
Summary: Beta-catenin promotes cardiac vascular SMC differentiation through Wnt-driven transcription; a cardiovascular cell-fate outcome, not core function (TAS).
Reason: downstream Wnt-driven cardiac SMC fate
Supporting Evidence:
PMID:20299672
Epicardial-myocardial signaling directing coronary vasculogenesis.
GO:0060982 coronary artery morphogenesis
TAS
PMID:20299672
Epicardial-myocardial signaling directing coronary vasculoge... 		KEEP AS NON CORE
Summary: Beta-catenin shapes coronary artery formation via epicardial/endothelial Wnt transcription; a cardiovascular morphogenetic outcome (TAS), not core function.
Reason: downstream Wnt-driven coronary morphogenesis
Supporting Evidence:
PMID:20299672
Epicardial-myocardial signaling directing coronary vasculogenesis.
GO:0060983 epicardium-derived cardiac vascular smooth muscle cell differentiation
TAS
PMID:20299672
Epicardial-myocardial signaling directing coronary vasculoge... 		KEEP AS NON CORE
Summary: Beta-catenin drives epicardium-derived SMC differentiation through Wnt transcription; a cardiovascular cell-fate outcome (TAS), not core function.
Reason: downstream Wnt-driven epicardial SMC fate
Supporting Evidence:
PMID:20299672
Epicardial-myocardial signaling directing coronary vasculogenesis.
GO:0072132 mesenchyme morphogenesis
TAS
PMID:20299672
Epicardial-myocardial signaling directing coronary vasculoge... 		KEEP AS NON CORE
Summary: Beta-catenin shapes mesenchymal tissue morphogenesis via Wnt transcription and adhesion; a morphogenetic outcome (TAS) of its dual role.
Reason: downstream of Wnt/adhesion mesenchyme morphogenesis
Supporting Evidence:
PMID:20299672
Epicardial-myocardial signaling directing coronary vasculogenesis.
GO:0140297 DNA-binding transcription factor binding
IPI
PMID:17331723
Inhibitory Gli3 activity negatively regulates Wnt/beta-caten... 		ACCEPT
Summary: Beta-catenin binds TCF/LEF DNA-binding transcription factors to coactivate Wnt target genes; core to its nuclear Wnt-effector role.
Reason: Core Wnt: direct TCF/LEF coactivation (IPI); foundational MF for the transcriptional arm.
Supporting Evidence:
PMID:17331723
Inhibitory Gli3 activity negatively regulates Wnt/beta-catenin signaling.
GO:0005515 protein binding
IPI
PMID:16611247
Human scribble, a novel tumor suppressor identified as a tar... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:16611247
Human scribble, a novel tumor suppressor identified as a target of high-risk HPV E6 for ubiquitin-mediated degradation, interacts with adenomatous polyposis coli.
GO:0005515 protein binding
IPI
PMID:19458197
Scribble interacts with beta-catenin to localize synaptic ve... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:19458197
Scribble interacts with beta-catenin to localize synaptic vesicles to synapses.
GO:0005515 protein binding
IPI
PMID:10954424
The mammalian homologue of the Caenorhabditis elegans polari... 		MARK AS OVER ANNOTATED
Summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
Reason: Generic MF over-annotation.
Supporting Evidence:
PMID:10954424
The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1.
GO:0019903 protein phosphatase binding
IPI
PMID:16973135
Intracellular substrates of brain-enriched receptor protein ... 		KEEP AS NON CORE
Summary: Protein-phosphatase binding (e.g. PTPN6/PTPRJ) regulates tyrosine-phosphorylation of junctional beta-catenin, a regulatory interaction.
Reason: Regulatory partner; IBA/IPI, non-core.
Supporting Evidence:
PMID:16973135
Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT).
GO:0005829 cytosol
TAS
Reactome:R-MMU-209096 		ACCEPT
Summary: Beta-catenin has a cytosolic pool subject to destruction-complex regulation and Wnt-dependent stabilization.
Reason: Genuine pool; IDA/TAS-supported.

Core Functions

Beta-catenin binds cadherins and alpha-catenin in adherens junctions to support cadherin-mediated cell-cell adhesion.

Molecular Function:
cadherin binding
Directly Involved In:
cell-cell adhesion cell-cell adhesion mediated by cadherin
Cellular Locations:
adherens junction cell-cell junction plasma membrane
In Complex:
catenin complex
Supporting Evidence:
  • file:mouse/Ctnnb1/Ctnnb1-deep-research.md
    Beta-catenin is a key cytoplasmic component of the cadherin-catenin complex at adherens junctions
  • file:mouse/Ctnnb1/Ctnnb1-deep-research-falcon.md
    beta-catenin supports adherens junction integrity by binding the cytoplasmic tail of E-cadherin and linking to alpha-catenin/actin-associated structures.

Stabilized beta-catenin acts with TCF/LEF transcription factors as a transcriptional coactivator in canonical Wnt signaling.

Molecular Function:
transcription coactivator activity
Directly Involved In:
canonical Wnt signaling pathway positive regulation of transcription by RNA polymerase II
Cellular Locations:
nucleus nucleoplasm
In Complex:
beta-catenin-TCF complex
Supporting Evidence:
  • file:mouse/Ctnnb1/Ctnnb1-deep-research.md
    In the nucleus, beta-catenin acts as a co-activator for TCF/LEF transcription factors
  • file:mouse/Ctnnb1/Ctnnb1-deep-research-falcon.md
    beta-catenin acts as the central transcriptional effector of canonical Wnt/beta-catenin signaling, accumulating and entering the nucleus when stabilized to co-activate TCF/LEF-dependent transcription.

References

GO_REF:0000008
Gene Ontology annotation by the MGI curatorial staff, curated orthology
PMID:10662781
Requirement for beta-catenin in anterior-posterior axis formation in mice.
PMID:11371349
beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin.
PMID:12194849
Formation of multiple hearts in mice following deletion of beta-catenin in the embryonic endoderm.
PMID:12235125
Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor.
PMID:12464179
Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.
PMID:12717450
A role for Wnt signalling in self-renewal of haematopoietic stem cells.
PMID:12813461
Activation of beta-catenin in prostate epithelium induces hyperplasias and squamous transdifferentiation.
PMID:12885771
beta-Catenin is required for specification of proximal/distal cell fate during lung morphogenesis.
PMID:12923052
Genetic interaction between Wnt/beta-catenin and BMP receptor signaling during formation of the AER and the dorsal-ventral axis in the limb.
PMID:12975353
The conditional inactivation of the beta-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility.
PMID:14608382
Deletion of beta-catenin impairs T cell development.
PMID:14622577
Role of beta-catenin in synaptic vesicle localization and presynaptic assembly.
PMID:15131783
Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin.
PMID:15708565
Effects of canonical Wnt signaling on dorso-ventral specification of the mouse telencephalon.
PMID:15866163
Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
PMID:15866165
Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
PMID:15907834
Wnt/beta-catenin signaling acts upstream of N-myc, BMP4, and FGF signaling to regulate proximal-distal patterning in the lung.
PMID:16040629
Beta-catenin regulates differentiation of respiratory epithelial cells in vivo.
PMID:16102745
The duality of beta-catenin function: a requirement in lens morphogenesis and signaling suppression of lens fate in periocular ectoderm.
PMID:16478791
APC inhibits ERK pathway activation and cellular proliferation induced by RAS.
PMID:16621792
Membrane localization of adenomatous polyposis coli protein at cellular protrusions: targeting sequences and regulation by beta-catenin.
PMID:16818445
Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis.
PMID:17537789
Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development.
PMID:17706960
Persistent expression of stabilized beta-catenin delays maturation of radial glial cells into intermediate progenitors.
PMID:18231602
Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
PMID:18533146
An FGF-WNT gene regulatory network controls lung mesenchyme development.
PMID:18635608
Tissue-specific requirements of beta-catenin in external genitalia development.
PMID:19023080
Canonical Wnt signaling regulates organ-specific assembly and differentiation of CNS vasculature.
PMID:19060336
A Wnt7b-dependent pathway regulates the orientation of epithelial cell division and establishes the cortico-medullary axis of the mammalian kidney.
PMID:19129494
Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis.
PMID:19154719
Nrarp coordinates endothelial Notch and Wnt signaling to control vessel density in angiogenesis.
PMID:19204372
Both the RGS domain and the six C-terminal amino acids of mouse Axin are required for normal embryogenesis.
PMID:19503085
HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction.
PMID:19619491
Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
PMID:19620969
A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate.
PMID:19690384
Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.
PMID:20043884
Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling within the Apical Ectodermal Ridge (AER) regulates interdigit formation.
PMID:20454446
WNT4/beta-catenin pathway maintains female germ cell survival by inhibiting activin betaB in the mouse fetal ovary.
PMID:20503375
Expression analysis of an evolutionarily conserved metallophosphodiesterase gene, Mpped1, in the normal and beta-catenin-deficient malformed dorsal telencephalon.
PMID:21937711
ASPM regulates Wnt signaling pathway activity in the developing brain.
PMID:22102609
Increased Ξ²-catenin activity in the anterior neural plate induces ectopic mid-hindbrain characteristics.
PMID:22723415
Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
PMID:23824574
Wnt/Ξ²-catenin signalling regulates Sox17 expression and is essential for organizer and endoderm formation in the mouse.
PMID:25083995
Canonical WNT signaling components in vascular development and barrier formation.
PMID:28463231
Disruption of lineage specification in adult pulmonary mesenchymal progenitor cells promotes microvascular dysfunction.
PMID:8582267
Lack of beta-catenin affects mouse development at gastrulation.
PMID:9230313
The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara.
GO_REF:0000119
Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs.
PMID:10631168
Hippocampus development and generation of dentate gyrus granule cells is regulated by LEF1.
PMID:12551949
Lymphoid enhancer factor-1 and beta-catenin inhibit Runx2-dependent transcriptional activation of the osteocalcin promoter.
PMID:12569130
Ectodermal Wnt3/beta-catenin signaling is required for the establishment and maintenance of the apical ectodermal ridge.
PMID:15024079
Brn-2 expression controls melanoma proliferation and is directly regulated by beta-catenin.
PMID:15371327
Wnt/beta-catenin signaling is sufficient and necessary for synovial joint formation.
PMID:15576404
Sequential roles of Hedgehog and Wnt signaling in osteoblast development.
PMID:15729346
Pax3 functions at a nodal point in melanocyte stem cell differentiation.
PMID:15778706
Wnt signalling induces maturation of Paneth cells in intestinal crypts.
PMID:15781477
Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation.
PMID:15802266
Essential role of beta-catenin in postnatal bone acquisition.
PMID:16025118
Loss of adenomatous polyposis coli gene function disrupts thymic development.
PMID:16192304
Beta-catenin is essential for pancreatic acinar but not islet development.
PMID:16581771
CCN1/Cyr61 is regulated by the canonical Wnt signal and plays an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells.
PMID:16678101
Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
PMID:16936075
The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 expression during somitogenesis.
PMID:17055474
The stabilization of beta-catenin leads to impaired primordial germ cell development via aberrant cell cycle progression.
PMID:17128274
Wnt-beta-catenin signaling initiates taste papilla development.
PMID:17532316
Essential roles of mesenchyme-derived beta-catenin in mouse MΓΌllerian duct morphogenesis.
PMID:17767158
Modulation of morphogenesis by noncanonical Wnt signaling requires ATF/CREB family-mediated transcriptional activation of TGFbeta2.
PMID:18316368
Protein encoded by the Axin(Fu) allele effectively down-regulates Wnt signaling but exerts a dominant negative effect on c-Jun N-terminal kinase signaling.
PMID:18692041
Bmp4 is required for tracheal formation: a novel mouse model for tracheal agenesis.
PMID:19056892
A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors.
PMID:19282366
Genetic interactions of the androgen and Wnt/beta-catenin pathways for the masculinization of external genitalia.
PMID:19515974
Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS.
PMID:19686689
Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut.
PMID:19718027
Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia.
PMID:19805295
beta-Catenin promotes respiratory progenitor identity in mouse foregut.
PMID:20159597
Characterization and in vivo pharmacological rescue of a Wnt2-Gata6 pathway required for cardiac inflow tract development.
PMID:20627076
The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/Notch signaling.
PMID:21075118
Biochemical and structural characterization of Ξ²-catenin interactions with nonphosphorylated and CK2-phosphorylated Lef-1.
PMID:21750544
The Wnt3a/Ξ²-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program.
PMID:22956852
Integration of Ξ²-catenin, sirtuin, and FOXO signaling protects from mutant huntingtin toxicity.
PMID:24309208
Wnt/Ξ²-catenin signaling in dermal condensates is required for hair follicle formation.
PMID:27713508
Conditional Knockout of Breast Carcinoma Amplified Sequence 2 (BCAS2) in Mouse Forebrain Causes Dendritic Malformation via Ξ²-catenin.
PMID:31222549
The Shisa3 knockout mouse exhibits normal bone phenotype.
GO_REF:0000024
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GO_REF:0000033
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GO_REF:0000043
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GO_REF:0000044
TODO: Fetch title
GO_REF:0000096
TODO: Fetch title
GO_REF:0000117
TODO: Fetch title
GO_REF:0000120
TODO: Fetch title
PMID:10318824
Functional domains of axin. Importance of the C terminus as an oligomerization domain.
PMID:10330403
Domains of axin involved in protein-protein interactions, Wnt pathway inhibition, and intracellular localization.
PMID:10481074
A GSK3-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed phosphorylation of axin and beta-catenin.
PMID:10873669
Identification of a novel beta-catenin-interacting protein.
PMID:10882138
Structure of the dimerization and beta-catenin-binding region of alpha-catenin.
PMID:10898789
Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein.
PMID:10954424
The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1.
PMID:11104755
Substitution of a glycogen synthase kinase-3beta phosphorylation site in presenilin 1 separates presenilin function from beta-catenin signaling.
PMID:11121423
The cadherin cytoplasmic domain is unstructured in the absence of beta-catenin. A possible mechanism for regulating cadherin turnover.
PMID:11262227
Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
PMID:11348595
The structure of the beta-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by beta-catenin.
PMID:11590244
alphaT-catenin: a novel tissue-specific beta-catenin-binding protein mediating strong cell-cell adhesion.
PMID:11731229
FAM deubiquitylating enzyme is essential for preimplantation mouse embryo development.
PMID:11731231
Dynamic expression and nuclear accumulation of beta-catenin during the development of hair follicle-derived structures.
PMID:11731265
Expression of Tcf/Lef and sFrp and localization of beta-catenin in the developing mouse lung.
PMID:11872843
Colorectal cancer in mice genetically deficient in the mucin Muc2.
PMID:12040017
Mouse mammary epithelial cells express the Na-K-Cl cotransporter, NKCC1: characterization, localization, and involvement in ductal development and morphogenesis.
PMID:12055200
Regulation of Wnt signaling during adipogenesis.
PMID:12181493
TCL1 participates in early embryonic development and is overexpressed in human seminomas.
PMID:12203715
Localization of the novel Xin protein to the adherens junction complex in cardiac and skeletal muscle during development.
PMID:12408825
ICAT inhibits beta-catenin binding to Tcf/Lef-family transcription factors and the general coactivator p300 using independent structural modules.
PMID:12421363
Axin negatively affects tau phosphorylation by glycogen synthase kinase 3beta.
PMID:12432063
Protein kinase CKII regulates the interaction of beta-catenin with alpha-catenin and its protein stability.
PMID:12494996
Loss of desmoglein 2 suggests essential functions for early embryonic development and proliferation of embryonal stem cells.
PMID:12611902
Regulation of the SHP-2 tyrosine phosphatase by a novel cholesterol- and cell confluence-dependent mechanism.
PMID:12695331
NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions.
PMID:12861022
T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors.
PMID:12874278
The PDZ protein tax-interacting protein-1 inhibits beta-catenin transcriptional activity and growth of colorectal cancer cells.
PMID:12949260
Wnt4 overexpression disrupts normal testicular vasculature and inhibits testosterone synthesis by repressing steroidogenic factor 1/beta-catenin synergy.
PMID:14597196
Overexpression of Sonic Hedgehog suppresses embryonic hair follicle morphogenesis.
PMID:14625387
Foxj1 is required for apical localization of ezrin in airway epithelial cells.
PMID:14647292
Mammalian formin-1 participates in adherens junctions and polymerization of linear actin cables.
PMID:14657280
Lamellipodium extension and cadherin adhesion: two cell responses to cadherin activation relying on distinct signalling pathways.
PMID:14687547
RORalpha coordinates reciprocal signaling in cerebellar development through sonic hedgehog and calcium-dependent pathways.
PMID:14691142
alpha3beta1 integrin-CD151, a component of the cadherin-catenin complex, regulates PTPmu expression and cell-cell adhesion.
PMID:14758363
The hyh mutation uncovers roles for alpha Snap in apical protein localization and control of neural cell fate.
PMID:14960280
Ozz-E3, a muscle-specific ubiquitin ligase, regulates beta-catenin degradation during myogenesis.
PMID:14981260
Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of beta-catenin.
PMID:15023525
Ksp-cadherin is a functional cell-cell adhesion molecule related to LI-cadherin.
PMID:15037549
Loss of cell polarity causes severe brain dysplasia in Lgl1 knockout mice.
PMID:15057752
Beta-catenin is temporally regulated during normal liver development.
PMID:15110721
Sox1 acts through multiple independent pathways to promote neurogenesis.
PMID:15148305
Mammalian Fat1 cadherin regulates actin dynamics and cell-cell contact.
PMID:15226261
Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization.
PMID:15292239
Defects in cell adhesion and the visceral endoderm following ablation of nonmuscle myosin heavy chain II-A in mice.
PMID:15314168
Cyclin D1 genetic heterozygosity regulates colonic epithelial cell differentiation and tumor number in ApcMin mice.
PMID:15327768
Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation.
PMID:15525667
Stabilization of beta-catenin in the mouse zygote leads to premature epithelial-mesenchymal transition in the epiblast.
PMID:15574752
Role of a BCL9-related beta-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling.
PMID:15645444
Gene expression profile analysis of mouse colon embryonic development.
PMID:15673614
Wnt10b deficiency promotes coexpression of myogenic and adipogenic programs in myoblasts.
PMID:15775979
E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions.
PMID:15834408
The KIF3 motor transports N-cadherin and organizes the developing neuroepithelium.
PMID:15905404
Functional interaction between beta-catenin and FOXO in oxidative stress signaling.
PMID:15908431
MAGI1 recruits Dll1 to cadherin-based adherens junctions and stabilizes it on the cell surface.
PMID:15987773
Forkhead box A1 regulates prostate ductal morphogenesis and promotes epithelial cell maturation.
PMID:16199027
Vezatin, a protein associated to adherens junctions, is required for mouse blastocyst morphogenesis.
PMID:16249236
Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network.
PMID:16293619
Thermodynamics of beta-catenin-ligand interactions: the roles of the N- and C-terminal tails in modulating binding affinity.
PMID:16364283
Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development.
PMID:16368433
Deficient E-cadherin adhesion in C57BL/6J-Min/+ mice is associated with increased tyrosine kinase activity and RhoA-dependent actomyosin contractility.
PMID:16418220
Desmocollin 3 is required for pre-implantation development of the mouse embryo.
PMID:16439479
Foxf1 and Foxf2 control murine gut development by limiting mesenchymal Wnt signaling and promoting extracellular matrix production.
PMID:16481394
The transitional junction: a new functional subcellular domain at the intercalated disc.
PMID:16489008
Patched1 functions as a gatekeeper by promoting cell cycle progression.
PMID:16611247
Human scribble, a novel tumor suppressor identified as a target of high-risk HPV E6 for ubiquitin-mediated degradation, interacts with adenomatous polyposis coli.
PMID:16678815
Lef1 is required for the transition of Wnt signaling from mesenchymal to epithelial cells in the mouse embryonic mammary gland.
PMID:16740478
Apc tumor suppressor gene is the "zonation-keeper" of mouse liver.
PMID:16858399
C3G regulates the size of the cerebral cortex neural precursor population.
PMID:16892058
The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface.
PMID:16962386
Tissue, cellular and sub-cellular localization of the Vangl2 protein during embryonic development: effect of the Lp mutation.
PMID:16973135
Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT).
PMID:16989802
Levels of mesenchymal FGFR2 signaling modulate smooth muscle progenitor cell commitment in the lung.
PMID:17130295
Distinct subdomain organization and molecular composition of a tight junction with adherens junction features.
PMID:17331723
Inhibitory Gli3 activity negatively regulates Wnt/beta-catenin signaling.
PMID:17535849
A unique and specific interaction between alphaT-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs.
PMID:17544522
Targeted disruption of the murine large nuclear KIAA1440/Ints1 protein causes growth arrest in early blastocyst stage embryos and eventual apoptotic cell death.
PMID:17560563
Fgf10 dosage is critical for the amplification of epithelial cell progenitors and for the formation of multiple mesenchymal lineages during lung development.
PMID:17596282
Unique mechanisms of growth regulation and tumor suppression upon Apc inactivation in the pancreas.
PMID:17615359
Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88.
PMID:17666436
Shroom2, a myosin-VIIa- and actin-binding protein, directly interacts with ZO-1 at tight junctions.
PMID:17671182
Haploinsufficiency of KrΓΌppel-like factor 4 promotes adenomatous polyposis coli dependent intestinal tumorigenesis.
PMID:17920587
FERM protein EPB41L5 is a novel member of the mammalian CRB-MPP5 polarity complex.
PMID:18202148
Cooperative control via lymphoid enhancer factor 1/T cell factor 3 and estrogen receptor-alpha for uterine gene regulation by estrogen.
PMID:18632848
SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability.
PMID:18636119
Coxsackievirus and adenovirus receptor (CAR) mediates atrioventricular-node function and connexin 45 localization in the murine heart.
PMID:18816447
Diverse roles of E-cadherin in the morphogenesis of the submandibular gland: insights into the formation of acinar and ductal structures.
PMID:18978355
Overexpression of TEAD-1 in transgenic mouse striated muscles produces a slower skeletal muscle contractile phenotype.
PMID:19107203
Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling.
PMID:19112489
Gata3 acts downstream of beta-catenin signaling to prevent ectopic metanephric kidney induction.
PMID:19122665
Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis.
PMID:19151727
Regulation of cardiovascular development and integrity by the heart of glass-cerebral cavernous malformation protein pathway.
PMID:19213727
Wnt11 promotes osteoblast maturation and mineralization through R-spondin 2.
PMID:19458197
Scribble interacts with beta-catenin to localize synaptic vesicles to synapses.
PMID:19497282
Wnt7a activates the planar cell polarity pathway to drive the symmetric expansion of satellite stem cells.
PMID:19725955
Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification.
PMID:19796622
Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors.
PMID:19850029
A critical role for sFRP proteins in maintaining caudal neural tube closure in mice via inhibition of BMP signaling.
PMID:19966784
Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closure.
PMID:20016102
The small GTPase Rac1 regulates auditory hair cell morphogenesis.
PMID:20089884
Milk secretion and ejection are impaired in the mammary gland of mice harboring a Cx43 mutant while expression and localization of tight and adherens junction proteins remain unchanged.
PMID:20299672
Epicardial-myocardial signaling directing coronary vasculogenesis.
PMID:20300119
Conductin/axin2 and Wnt signalling regulates centrosome cohesion.
PMID:20371816
LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1g) in thalamic neurons of the adult brain.
PMID:20399730
The apical complex couples cell fate and cell survival to cerebral cortical development.
PMID:20413591
The TRPV4 channel contributes to intercellular junction formation in keratinocytes.
PMID:20531388
Mutant huntingtin-impaired degradation of beta-catenin causes neurotoxicity in Huntington's disease.
PMID:20802155
Sox17 modulates Wnt3A/beta-catenin-mediated transcriptional activation of the Lef-1 promoter.
PMID:20837657
Abelson family kinases regulate Frizzled planar cell polarity signaling via Dsh phosphorylation.
PMID:21103407
The leukemia-associated Mllt10/Af10-Dot1l are Tcf4/Ξ²-catenin coactivators essential for intestinal homeostasis.
PMID:21262216
The zinc finger transcription factors Osr1 and Osr2 control synovial joint formation.
PMID:21325504
Frizzled3 is required for neurogenesis and target innervation during sympathetic nervous system development.
PMID:21350016
Canonical Wnt9b signaling balances progenitor cell expansion and differentiation during kidney development.
PMID:21377456
Grainyhead-like 2 regulates neural tube closure and adhesion molecule expression during neural fold fusion.
PMID:21393547
A polarized epithelium organized by beta- and alpha-catenin predates cadherin and metazoan origins.
PMID:21512031
Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size.
PMID:21552260
Nemo kinase phosphorylates Ξ²-catenin to promote ommatidial rotation and connects core PCP factors to E-cadherin-Ξ²-catenin.
PMID:21730140
Ezrin-mediated apical integrity is required for intestinal homeostasis.
PMID:21751375
Functional analysis of novel phosphorylation sites of CREB-binding protein using mass spectrometry and mammalian two-hybrid assays.
PMID:21752258
A Wnt1 regulated Frizzled-1/Ξ²-Catenin signaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: Therapeutical relevance for neuron survival and neuroprotection.
PMID:21991325
RSPO1/Ξ²-catenin signaling pathway regulates oogonia differentiation and entry into meiosis in the mouse fetal ovary.
PMID:21991385
Adhesion protein VSIG1 is required for the proper differentiation of glandular gastric epithelia.
PMID:22083958
Histone H1 recruitment by CHD8 is essential for suppression of the Wnt-Ξ²-catenin signaling pathway.
PMID:22139371
Bardet-Biedl syndrome 3 (Bbs3) knockout mouse model reveals common BBS-associated phenotypes and Bbs3 unique phenotypes.
PMID:22645310
Prolyl isomerase Pin1 regulates neuronal differentiation via Ξ²-catenin.
PMID:22665494
mrhl RNA, a long noncoding RNA, negatively regulates Wnt signaling through its protein partner Ddx5/p68 in mouse spermatogonial cells.
PMID:22899650
LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6.
PMID:23266329
Kruppel-like factor 5 controls villus formation and initiation of cytodifferentiation in the embryonic intestinal epithelium.
PMID:23273993
Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties.
PMID:23377854
Physiological role of Ξ²-catenin/TCF signaling in neurons of the adult brain.
PMID:23460868
Ξ²-catenin is essential for efficient in vitro premyogenic mesoderm formation but can be partially compensated by retinoic acid signalling.
PMID:23610556
A positive feedback loop involving Gcm1 and Fzd5 directs chorionic branching morphogenesis in the placenta.
PMID:23740243
Activation of the transcription factor GLI1 by WNT signaling underlies the role of SULFATASE 2 as a regulator of tissue regeneration.
PMID:23856522
Jmjd3 controls mesodermal and cardiovascular differentiation of embryonic stem cells.
PMID:23863479
Tumor suppressor Nf2 limits expansion of the neural progenitor pool by inhibiting Yap/Taz transcriptional coactivators.
PMID:24046456
Flotillin microdomains stabilize cadherins at cell-cell junctions.
PMID:24191021
Sox9 plays multiple roles in the lung epithelium during branching morphogenesis.
PMID:24338362
POPX2 phosphatase regulates the KIF3 kinesin motor complex.
PMID:24681597
Kindlin-1 controls Wnt and TGF-Ξ² availability to regulate cutaneous stem cell proliferation.
PMID:24847765
From inception to output, Tcf1 and Lef1 safeguard development of T cells and innate immune cells.
PMID:25009587
Depletion of canonical Wnt signaling components has a neuroprotective effect on midbrain dopaminergic neurons in an MPTP-induced mouse model of Parkinson's disease.
PMID:25232112
Dlg5 regulates dendritic spine formation and synaptogenesis by controlling subcellular N-cadherin localization.
PMID:25535395
Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway.
PMID:25873176
TGIF governs a feed-forward network that empowers Wnt signaling to drive mammary tumorigenesis.
PMID:25961718
Resveratrol-Induced Vascular Progenitor Differentiation towards Endothelial Lineage via MiR-21/Akt/Ξ²-Catenin Is Protective in Vessel Graft Models.
PMID:25979161
Transmembrane protein 64 reciprocally regulates osteoblast and adipocyte differentiation by modulating Wnt/Ξ²-catenin signaling.
PMID:26371318
Lhx2 regulates the timing of Ξ²-catenin-dependent cortical neurogenesis.
PMID:26787558
SPECC1L deficiency results in increased adherens junction stability and reduced cranial neural crest cell delamination.
PMID:26893351
The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis.
PMID:27015268
Plakophilin-1, a Novel Wnt Signaling Regulator, Is Critical for Tooth Development and Ameloblast Differentiation.
PMID:27375112
Antagonistic Regulation of Intercellular Cohesion by Plakophilins 1 and 3.
PMID:28641114
A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Complexes in Stabilizing Spines and Functional Synapses in the Neocortex.
PMID:29148101
Homeobox protein MSX-1 inhibits expression of bone morphogenetic protein 2, bone morphogenetic protein 4, and lymphoid enhancer-binding factor 1 via Wnt/Ξ²-catenin signaling to prevent differentiation of dental mesenchymal cells during the late bell stage.
PMID:29211732
The mouse Jhy gene regulates ependymal cell differentiation and ciliogenesis.
PMID:30389919
ARTS mediates apoptosis and regeneration of the intestinal stem cell niche.
PMID:30478225
TBX2 and TBX3 act downstream of canonical WNT signaling in patterning and differentiation of the mouse ureteric mesenchyme.
PMID:30659184
Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis.
PMID:31073040
LMBR1L regulates lymphopoiesis through Wnt/Ξ²-catenin signaling.
PMID:32533114
ADNP promotes neural differentiation by modulating Wnt/Ξ²-catenin signaling.
PMID:32868762
The cellular and molecular landscape of hypothalamic patterning and differentiation from embryonic to late postnatal development.
PMID:8555428
Immunotoxicologic effects of ethylene dibromide in the mouse and their modulation by the estrous cycle.
PMID:8821035
Expression of catenins during mouse embryonic development and in adult tissues.
PMID:8853988
Expression and cell membrane localization of catenins during mouse preimplantation development.
PMID:8909549
The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones.
PMID:9264463
A specific domain in alpha-catenin mediates binding to beta-catenin or plakoglobin.
PMID:9488439
Two members of the Tcf family implicated in Wnt/beta-catenin signaling during embryogenesis in the mouse.
PMID:9554852
Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta.
PMID:9950951
Nuclear localization of beta-catenin and loss of apical brush border actin in cystic tubules of bcl-2 -/- mice.
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file:mouse/Ctnnb1/Ctnnb1-deep-research-falcon.md
Falcon deep research synthesis for mouse Ctnnb1
  • Beta-catenin has two core molecular roles: cadherin-catenin adhesion at adherens junctions and canonical Wnt/TCF transcriptional coactivation.
    "beta-catenin is widely characterized as a multifunctional protein that supports adherens junction integrity by binding the cytoplasmic tail of E-cadherin and acts as the central transcriptional effector of canonical Wnt/beta-catenin signaling."
  • Ctnnb1 is a non-enzymatic adaptor and transcriptional coactivator whose functions are driven by partner-specific protein interactions.
    "Ctnnb1/beta-catenin is best annotated as a non-enzymatic adaptor and transcriptional co-activator whose primary molecular functions arise from protein-protein interactions rather than catalytic activity."

Suggested Questions for Experts

Q: How does Ξ²-catenin coordinate its dual roles in cell adhesion and Wnt signaling, and what mechanisms prevent crosstalk?

Q: What determines the tissue-specific requirements for Ξ²-catenin in development versus homeostasis?

Q: How do different Ξ²-catenin mutations lead to distinct developmental disorders and cancer types?

Q: What role does Ξ²-catenin play in stem cell maintenance and differentiation across different tissue types?

Suggested Experiments

Experiment: Single-cell RNA sequencing of tissues with conditional Ξ²-catenin knockout to map cell-type-specific transcriptional programs

Experiment: Super-resolution microscopy to study Ξ²-catenin dynamics between adherens junctions and the nucleus during Wnt signaling

Experiment: Cryo-EM structural determination of Ξ²-catenin in complex with different binding partners like cadherins and TCF/LEF

Experiment: Lineage tracing in mouse models to study Ξ²-catenin function in stem cell fate decisions during development and regeneration

Deep Research

Falcon

(Ctnnb1-deep-research-falcon.md)
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 25 citations 2026-05-03T17:13:45.301144

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research Report: Functional Annotation of mouse Ctnnb1 (Ξ²-catenin) (UniProt: Q02248)

1) Gene/protein identity verification (mandatory)

The UniProt accession Q02248 corresponds to Mus musculus Ctnnb1, encoding Ξ²-catenin, an armadillo-repeat protein with dual roles in cell–cell adhesion and canonical Wnt signaling (jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2, zhuang2023ctnnb1inneurodevelopmental pages 1-2). Recent reviews and primary studies describe Ξ²-catenin as a ~781-aa, ~88 kDa protein with an armadillo-repeat core and flexible terminal regions, consistent with UniProt’s β€œbelongs to Ξ²-catenin family” and ARM-like/Armadillo domain annotations (dev2023Ξ²catenininhibitorsin pages 1-2, dev2023Ξ²catenininhibitorsin pages 2-4).

2) Key concepts and definitions (current understanding)

2.1 Ξ²-catenin as a β€œmoonlighting” adhesion and signaling protein

Ξ²-catenin is widely characterized as a multifunctional (β€œmoonlighting”) protein that:
- Supports adherens junction (AJ) integrity by binding the cytoplasmic tail of E-cadherin (cadherin–catenin complex) and linking to Ξ±-catenin/actin-associated structures (dantzer2024specificfeaturesof pages 3-4, dev2023Ξ²catenininhibitorsin pages 1-2).
- Acts as the central transcriptional effector of canonical Wnt/Ξ²-catenin signaling, accumulating and entering the nucleus when stabilized to co-activate TCF/LEF-dependent transcription (dev2023Ξ²catenininhibitorsin pages 2-4, jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2).

2.2 Domain architecture and interaction logic

A recent 2023 synthesis breaks Ξ²-catenin into three principal regions:
- N-terminal regulatory domain (~aa 1–150), a major regulatory β€œhotspot” controlling stability (dev2023Ξ²catenininhibitorsin pages 2-4).
- Central armadillo repeat domain (~aa 141–664) with 12 ARM repeats, forming a binding groove for many partners (cadherins, APC, TCF/LEF, etc.) (dev2023Ξ²catenininhibitorsin pages 1-2, dev2023Ξ²catenininhibitorsin pages 2-4).
- C-terminal domain (~aa 665–781) that contributes transactivation/co-activator function and is structurally flexible/disordered (dev2023Ξ²catenininhibitorsin pages 2-4, dantzer2024specificfeaturesof pages 3-4).

A key functional implication is that overlapping binding surfaces in the ARM-repeat groove can enforce mutual exclusivity among interaction partners (e.g., cadherin binding at junctions versus transcriptional partners), providing a structural basis for switching between adhesion-associated and signaling-associated states (dev2023Ξ²catenininhibitorsin pages 1-2).

2.3 Canonical Wnt pathway: the destruction complex and Ξ²-catenin turnover

In the β€œWnt-off” state, cytoplasmic Ξ²-catenin is targeted for degradation by a destruction complex assembled from APC, AXIN, CK1Ξ±, and GSK3 kinases (dantzer2024specificfeaturesof pages 3-4, zhuang2023ctnnb1inneurodevelopmental pages 1-2). Sequential phosphorylation is a central mechanistic definition of Ξ²-catenin regulation:
- CK1Ξ± phosphorylates Ser45 (S45),
- followed by GSK3Ξ² phosphorylation at Thr41 (T41), Ser37 (S37), and Ser33 (S33),
- enabling recognition by Ξ²-TrCP (E3 ligase adaptor), ubiquitination, and proteasomal degradation (dev2023Ξ²catenininhibitorsin pages 2-4, dantzer2024specificfeaturesof pages 3-4).
Upon Wnt activation, this turnover is restrained, allowing Ξ²-catenin stabilization and nuclear transcriptional co-activation (zhuang2023ctnnb1inneurodevelopmental pages 1-2).

2.4 Subcellular localization

Ξ²-catenin is found at adherens junctions, in the cytoplasm, and in the nucleus, with the balance controlled by junctional binding and destruction-complex-mediated turnover (dantzer2024specificfeaturesof pages 3-4, jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2). In mouse retinal pigment epithelium (RPE), Ξ²-catenin is described as primarily AJ-localized but can dissociate and accumulate in the nucleus in remodeling contexts (jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2).

3) Recent developments and latest research (prioritizing 2023–2024)

3.1 2024: Discovery of an intestine-specific Ctnnb1 enhancer that controls Wnt dosage and tumorigenesis

Hua et al. (eLife, Sep 2024) identified a cis-regulatory element upstream of mouse Ctnnb1, termed ieCtnnb1 (intestinal enhancer of Ctnnb1), with activity concentrated at the base of small intestinal crypts and across the large-intestine epithelium (hua2024actnnb1enhancer pages 1-2, hua2024actnnb1enhancer pages 3-6). Key mechanistic and quantitative findings include:
- Ctnnb1Ξ”i.enh mice showed reduced crypt Ctnnb1 mRNA (βˆ’26.5% small intestine; βˆ’22.3% large intestine) and reduced Ξ²-catenin protein in crypts (nuclear βˆ’49.5%, cytosolic βˆ’29.8%) (hua2024actnnb1enhancer pages 6-8).
- Single-cell and marker analyses indicated altered epithelial composition, including a 49.2% decrease in Paneth cell proportion, alongside reduced expression of Paneth/secretory programs and reduced proliferation (Ki67+ βˆ’16.1%, EdU+ βˆ’21.9%) (hua2024actnnb1enhancer pages 6-8).
- In an ApcMin/+ intestinal tumor context, ieCtnnb1 enhancer deletion strongly suppressed Wnt-driven tumorigenesis and extended median survival from 165 to 255 days (hua2024actnnb1enhancer pages 8-9).
This work reframes Ctnnb1 regulation as not only post-translational (destruction complex) but also enhancer-controlled transcriptional dosage, with direct consequences for homeostasis and cancer risk (hua2024actnnb1enhancer pages 1-2, hua2024actnnb1enhancer pages 6-8).

URL/DOI: https://doi.org/10.7554/elife.98238 (Sep 2024) (hua2024actnnb1enhancer pages 1-2)

3.2 2024: Immune-cell-specific Ξ²-catenin activation rewires ILC3 chromatin and promotes intestinal inflammation

Hao et al. (Nature Communications, Apr 2024) report Ξ²-catenin increases in intestinal ILC3s from IBD/CRC patients and show that activating Wnt/Ξ²-catenin signaling in mouse ILC3s suppresses RORΞ³t and impairs ILC3 proliferation and cytokine function, leading to ILC3 deficiency and intestinal inflammation (hao2024dysregulationofwntΞ²catenin pages 1-2).

Mechanistically, Ξ²-catenin acts via its transcriptional partner TCF-1, but the pathway does not simply repress RORΞ³t directly; instead, it involves chromatin-level remodeling and suppression of JunB, which is essential for RORΞ³t expressionβ€”summarized as a TCF-1/JunB/RORΞ³t axis (hao2024dysregulationofwntΞ²catenin pages 1-2, hao2024dysregulationofwntΞ²catenin pages 7-8).

In vivo genetic activation used Ctnnb1 exon 3 stabilization alleles such as RorccreCtnnb1ex3fl/wt and inducible CreERT2Ctnnb1ex3fl/wt systems (hao2024dysregulationofwntΞ²catenin pages 5-7, hao2024dysregulationofwntΞ²catenin pages 11-12). In inducible settings, the authors report that nearly half of ILC3s became Ξ²-catenin+ by day 6 (hao2024dysregulationofwntΞ²catenin pages 4-5).

URL/DOI: https://doi.org/10.1038/s41467-024-45616-1 (Apr 2024) (hao2024dysregulationofwntΞ²catenin pages 1-2)

3.3 2024: Junctional mechanotransduction contextβ€”Ξ²-catenin dependence via Ξ±-catenin binding

Although force-sensing at adherens junctions is often attributed to Ξ±-catenin/vinculin mechanics, 2024 work reinforces that Ξ²-catenin binding is structurally prerequisite for Ξ±-catenin’s integration into the cadherin–catenin complex. Quinn et al. (MBoC, May 2024) report that an Ξ±-catenin form lacking the Ξ²-catenin-binding domain fails to associate with the cadherin–catenin complex and cannot directly participate in the cadherin–catenin catch-bond mechanism (quinn2024Ξ±cateninmiddleand pages 2-4). This positions Ξ²-catenin as a required adaptor for the mechanotransduction-competent junctional assembly.

URL/DOI: https://doi.org/10.1091/mbc.e23-01-0036 (May 2024) (quinn2024Ξ±cateninmiddleand pages 2-4)

3.4 2024: Direct chemical tractabilityβ€”covalent degraders of Ξ²-catenin

Gowans et al. (JACS, Jun 2024) demonstrate a chemoproteomic strategy for directly targeting Ξ²-catenin (CTNNB1) using a cysteine-reactive monovalent covalent ligand EN83 that induces Ξ²-catenin depletion via a ubiquitin–proteasome-dependent mechanism (gowans2024covalentdegraderof pages 1-4). They mapped covalent modification to armadillo-domain cysteines C439, C466, C520, and C619 by MS/MS, with functional dependence on C466/C520/C619 for degradation phenotypes (gowans2024covalentdegraderof pages 4-7). Chemoproteomic selectivity analysis quantified 8,251 cysteines, with EN83 engaging C619 on CTNNB1 and 139 other targets >50%, while not engaging core Wnt components such as AXIN1, BTRC, or GSK3A/B in that profiling (gowans2024covalentdegraderof pages 4-7).

URL/DOI: https://doi.org/10.1021/jacs.4c05174 (Jun 2024) (gowans2024covalentdegraderof pages 1-4)

4) Current applications and real-world implementations

4.1 Functional genetics in mice: conditional loss/activation of Ctnnb1

Current experimental practice heavily relies on tissue-specific genetic perturbations:
- Enhancer deletion (CRISPR/Cas9) to modulate Ctnnb1 transcriptional dosage in a tissue-restricted manner (intestinal ieCtnnb1) (hua2024actnnb1enhancer pages 3-6, hua2024actnnb1enhancer pages 6-8).
- Cre/lox tissue-specific activation via exon-3-stabilized alleles (e.g., RorccreCtnnb1ex3fl/wt, CreERT2Ctnnb1ex3fl/wt) to model persistent pathway activation in specific immune lineages and assess inflammation/host defense phenotypes (hao2024dysregulationofwntΞ²catenin pages 5-7, hao2024dysregulationofwntΞ²catenin pages 4-5).
- Cre/lox tissue-specific knockout in metabolic studies, including Ucp1-Cre;Ctnnb1flox/flox for adipose thermogenic biology (chen2023ctnnb1Ξ²catenininactivationin pages 2-5, chen2023ctnnb1Ξ²catenininactivationin pages 18-20).

4.2 Transcriptional readouts and pathway activity monitoring

Across 2023–2024 studies, pathway output is commonly operationalized by:
- Ξ²-catenin protein localization (nuclear/cytosolic) and immunostaining,
- and transcriptional readouts including Wnt targets such as Axin2 and Lgr5 (intestinal crypt/stem cell context), together with other Wnt-responsive genes (hua2024actnnb1enhancer pages 3-6, hua2024actnnb1enhancer pages 6-8).

4.3 Translational/biomedical implementation: targeting Wnt/Ξ²-catenin in cancer and immune contexts

Recent cancer-focused reviews emphasize that Ξ²-catenin’s nuclear accumulation drives oncogenic transcription (e.g., MYC, cyclin D1) and that its stability/localization are key therapeutic nodes (dev2023Ξ²catenininhibitorsin pages 2-4). The EN83 work provides a proof-of-concept that Ξ²-catenin can be destabilized by direct covalent targeting of ligandable cysteines, suggesting a potential route to overcome challenges of targeting a DNA-binding-deficient transcriptional co-activator (gowans2024covalentdegraderof pages 1-4, gowans2024covalentdegraderof pages 4-7).

5) Relevant statistics and data highlights (from recent studies)

Key quantitative datapoints useful for functional annotation include:
- Transcriptional dosage control (intestinal enhancer): Ctnnb1 mRNA decreased by 26.5% (SI crypts) and 22.3% (LI crypts); Ξ²-catenin protein decreased by 49.5% (nuclear) and 29.8% (cytosolic) (hua2024actnnb1enhancer pages 6-8).
- Cell-type composition and proliferation (intestinal crypts): Paneth cell proportion decreased 49.2%; Ki67+ cells decreased 16.1%; EdU+ cells decreased 21.9% (hua2024actnnb1enhancer pages 6-8).
- Tumorigenesis outcome: ApcMin/+ median survival increased from 165 to 255 days with ieCtnnb1 enhancer deletion (hua2024actnnb1enhancer pages 8-9).
- Adipose transcriptomics: Following CL-316,243 stimulation, eWAT showed 290 upregulated and 1607 downregulated genes (criterion: p<0.05, FC>1.5) in Ucp1-Cre Ctnnb1 knockout vs control (chen2023ctnnb1Ξ²catenininactivationin pages 5-8).
- Chemoproteomic targeting selectivity: EN83 profiling quantified 8,251 cysteines; 139 targets engaged >50%, with CTNNB1 C619 engagement and mapped covalent modifications to C439/C466/C520/C619 (gowans2024covalentdegraderof pages 4-7).

Expert synthesis (authoritative interpretation grounded in sources)

Ctnnb1/Ξ²-catenin is best annotated as a non-enzymatic adaptor and transcriptional co-activator whose primary molecular functions arise from protein–protein interactions rather than catalytic activity. Contemporary evidence supports a β€œtwo-pool” model: a junctional pool integrated into cadherin-mediated adhesion and a signaling pool whose abundance is governed by destruction-complex phosphorylation and, as shown recently in vivo, by tissue-specific transcriptional dosage control via enhancers (dev2023Ξ²catenininhibitorsin pages 2-4, hua2024actnnb1enhancer pages 6-8). Recent mouse genetics further illustrate that Ξ²-catenin’s transcriptional activity can dominate developmental specification (RPE) (jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2), while immune and metabolic systems show context-dependent Ξ²-catenin programs that reshape chromatin and lineage function (ILC3 inflammation axis) (hao2024dysregulationofwntΞ²catenin pages 1-2) or restrain thermogenic adipocyte differentiation (Ucp1-Cre knockout) (chen2023ctnnb1Ξ²catenininactivationin pages 2-5).

Summary tables

The following embedded tables provide a compact evidence map for functional annotation and recent applications.

Aspect Summary for mouse Ctnnb1 / Ξ²-catenin Representative mouse evidence Key 2023–2024 sources
Target identity Ctnnb1 in Mus musculus encodes Ξ²-catenin, an armadillo-repeat protein with dual adhesive and signaling roles; recent sources describe the protein as ~781 aa with a central ARM-repeat core, matching the UniProt Q02248 annotation and beta-catenin family assignment. (dev2023Ξ²catenininhibitorsin pages 1-2, jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2, zhuang2023ctnnb1inneurodevelopmental pages 1-2) Mouse RPE study explicitly refers to Ctnnb1 (Ξ²-catenin) and tests separation-of-function alleles in vivo. (jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2) Dev et al., 2023, Bioengineered, DOI: https://doi.org/10.1080/21655979.2023.2251696 (dev2023Ξ²catenininhibitorsin pages 1-2); Kim et al., 2023, Molecules and Cells, DOI: https://doi.org/10.14348/molcells.2023.0029 (jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2); Dantzer et al., 2024, Br J Cancer, DOI: https://doi.org/10.1038/s41416-024-02849-7 (dantzer2024specificfeaturesof pages 3-4)
Domain architecture N-terminal regulatory region (~aa 1–150) contains the major phospho-degron; central ARM-repeat core (~aa 141–664) has 12 armadillo repeats forming the interaction platform for cadherins, APC, TCF/LEF and other partners; C-terminal region (~aa 665–781) functions as a transcriptional activation/transactivation region and is structurally flexible/disordered. (dev2023Ξ²catenininhibitorsin pages 2-4, dantzer2024specificfeaturesof pages 3-4, dev2023Ξ²catenininhibitorsin pages 1-2) Mouse studies interpreting functionally distinct Ctnnb1 alleles rely on the separable transcriptional versus junctional activities encoded by these domains. (jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2) Dev et al., 2023, https://doi.org/10.1080/21655979.2023.2251696 (dev2023Ξ²catenininhibitorsin pages 2-4, dev2023Ξ²catenininhibitorsin pages 1-2); Dantzer et al., 2024, https://doi.org/10.1038/s41416-024-02849-7 (dantzer2024specificfeaturesof pages 3-4)
Key cellular localizations Ξ²-catenin localizes to adherens junctions at the plasma membrane, a cytoplasmic pool subject to destruction-complex control, and the nucleus where stabilized Ξ²-catenin acts as a transcriptional co-activator. Mouse RPE work notes predominant AJ localization with nuclear accumulation possible during epithelial remodeling/EMT-like contexts. (dantzer2024specificfeaturesof pages 3-4, jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2, zhuang2023ctnnb1inneurodevelopmental pages 1-2) In intestinal crypts, enhancer deletion lowered nuclear Ξ²-catenin by 49.5% and cytosolic Ξ²-catenin by 29.8%, providing direct localization-sensitive in vivo evidence in mouse tissue. (hua2024actnnb1enhancer pages 6-8) Kim et al., 2023, https://doi.org/10.14348/molcells.2023.0029 (jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2); Hua et al., 2024, eLife, https://doi.org/10.7554/elife.98238 (hua2024actnnb1enhancer pages 6-8); Dantzer et al., 2024, https://doi.org/10.1038/s41416-024-02849-7 (dantzer2024specificfeaturesof pages 3-4)
Core molecular function: adhesion At adherens junctions, Ξ²-catenin binds the cytoplasmic tail of E-cadherin and connects the cadherin complex to Ξ±-catenin and the actin cytoskeleton, supporting Ca2+-dependent cell-cell adhesion and epithelial integrity. Junctional release can contribute to the signaling-competent cytoplasmic pool. (dantzer2024specificfeaturesof pages 3-4, dev2023Ξ²catenininhibitorsin pages 1-2, dev2023Ξ²catenininhibitorsin pages 2-4) In mouse RPE, a junction-affinity–reduced mutant (Ctnnb1Y654E) could still substitute in specification assays, whereas a transcription-impaired mutant could not, helping distinguish adhesive from transcriptional requirements in vivo. (jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2) Dev et al., 2023, https://doi.org/10.1080/21655979.2023.2251696 (dev2023Ξ²catenininhibitorsin pages 2-4, dev2023Ξ²catenininhibitorsin pages 1-2); Kim et al., 2023, https://doi.org/10.14348/molcells.2023.0029 (jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2); Dantzer et al., 2024, https://doi.org/10.1038/s41416-024-02849-7 (dantzer2024specificfeaturesof pages 3-4)
Core molecular function: transcription In canonical Wnt signaling, stabilized Ξ²-catenin enters the nucleus, associates with TCF/LEF transcription factors, displaces Groucho/corepressors, and recruits co-activators such as BCL9, CBP, Pygopus, BRG1 to activate Wnt targets including MYC/c-Myc, CCND1/cyclin D1, LGR5, AXIN2. Ξ²-catenin itself does not bind DNA directly. (dev2023Ξ²catenininhibitorsin pages 2-4, farhat2024thebcatenininteractome pages 18-23, farhat2024thebcatenininteractome pages 6-12) Mouse RPE specification required transcriptionally competent Ctnnb1; constitutively active Ctnnb1Ξ”ex3 altered fate specification. In intestinal crypts, ieCtnnb1 enhancer loss reduced Wnt targets such as Axin2, Lgr5, Mmp7. (jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2, hua2024actnnb1enhancer pages 3-6, hua2024actnnb1enhancer pages 6-8) Dev et al., 2023, https://doi.org/10.1080/21655979.2023.2251696 (dev2023Ξ²catenininhibitorsin pages 2-4); Kim et al., 2023, https://doi.org/10.14348/molcells.2023.0029 (jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2); Hua et al., 2024, https://doi.org/10.7554/elife.98238 (hua2024actnnb1enhancer pages 3-6, hua2024actnnb1enhancer pages 6-8)
Core regulatory mechanism In the Wnt-off state, Ξ²-catenin is targeted by the destruction complex (APC, AXIN, CK1Ξ±, GSK3Ξ±/Ξ²) for sequential N-terminal phosphorylation: S45 by CK1Ξ±, then T41, S37, S33 by GSK3Ξ²; phosphorylated Ξ²-catenin is recognized by Ξ²-TrCP for ubiquitination and proteasomal degradation. Wnt activation suppresses this turnover, allowing accumulation and nuclear signaling. (dev2023Ξ²catenininhibitorsin pages 2-4, dantzer2024specificfeaturesof pages 3-4, zhuang2023ctnnb1inneurodevelopmental pages 1-2) Mouse experimental systems use pathway-activating alleles that remove exon 3 or otherwise stabilize Ξ²-catenin, and tissue-specific enhancer perturbation that lowers Ctnnb1 dosage and Wnt output in vivo. (hua2024actnnb1enhancer pages 6-8, hao2024dysregulationofwntΞ²catenin pages 1-2, hao2024dysregulationofwntΞ²catenin pages 11-12) Dev et al., 2023, https://doi.org/10.1080/21655979.2023.2251696 (dev2023Ξ²catenininhibitorsin pages 2-4); Dantzer et al., 2024, https://doi.org/10.1038/s41416-024-02849-7 (dantzer2024specificfeaturesof pages 3-4); Zhuang et al., 2023, https://doi.org/10.3389/fpsyt.2023.1143328 (zhuang2023ctnnb1inneurodevelopmental pages 1-2)
Representative mouse model: intestinal enhancer dosage control A newly defined ieCtnnb1 enhancer, active at the base of small-intestinal crypts and across large-intestinal epithelium, fine-tunes Ctnnb1 transcription and Wnt dosage. Homozygous enhancer knockout reduced crypt Ctnnb1 mRNA by 26.5% in small intestine and 22.3% in large intestine, reduced Ξ²-catenin protein, downregulated Wnt targets, decreased Paneth-cell proportion by 49.2%, and lowered Ki67+ and EdU+ proliferative cells by 16.1% and 21.9%, respectively. (hua2024actnnb1enhancer pages 1-2, hua2024actnnb1enhancer pages 3-6, hua2024actnnb1enhancer pages 6-8, hua2024actnnb1enhancer pages 2-3) In ApcMin/+ mice, enhancer loss markedly suppressed Wnt-driven tumorigenesis and prolonged median survival from 165 to 255 days. (hua2024actnnb1enhancer pages 8-9) Hua et al., 2024, https://doi.org/10.7554/elife.98238 (hua2024actnnb1enhancer pages 8-9, hua2024actnnb1enhancer pages 1-2, hua2024actnnb1enhancer pages 3-6, hua2024actnnb1enhancer pages 6-8, hua2024actnnb1enhancer pages 2-3)
Representative mouse model: RPE separation of function In mouse retinal pigment epithelium, Ctnnb1’s transcriptional activity was required for RPE specification, whereas reduced junctional affinity alone was tolerated. This supports a context where the pathway role dominates over the adhesive role during lineage specification. (jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2) Ctnnb1dm (transcription-impaired) failed to replace endogenous Ctnnb1 in RPE, Ctnnb1Y654E (reduced junction affinity) could substitute, and constitutively active Ctnnb1Ξ”ex3 redirected cell fate. (jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2) Kim et al., 2023, https://doi.org/10.14348/molcells.2023.0029 (jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2)
Representative mouse model: immune-cell-specific activation In ILC3 lineage cells, activated Ctnnb1 suppresses the TCF-1/JunB/RORΞ³t axis, impairing ILC3 proliferation/function and aggravating intestinal inflammation, illustrating a highly context-dependent transcriptional program downstream of Ξ²-catenin. (hao2024dysregulationofwntΞ²catenin pages 1-2, hao2024dysregulationofwntΞ²catenin pages 7-8, hao2024dysregulationofwntΞ²catenin pages 5-7, hao2024dysregulationofwntΞ²catenin pages 11-12) RorccreCtnnb1ex3fl/wt and CreERT2Ctnnb1ex3fl/wt models caused reduced ILC3 numbers, decreased IL-22/IL-17A-related function, and worsened DSS colitis; in inducible cultures, nearly half of ILC3s became Ξ²-catenin+ by day 6. (hao2024dysregulationofwntΞ²catenin pages 1-2, hao2024dysregulationofwntΞ²catenin pages 4-5) Hao et al., 2024, Nature Communications, https://doi.org/10.1038/s41467-024-45616-1 (hao2024dysregulationofwntΞ²catenin pages 1-2, hao2024dysregulationofwntΞ²catenin pages 5-7, hao2024dysregulationofwntΞ²catenin pages 11-12, hao2024dysregulationofwntΞ²catenin pages 4-5)
Representative mouse model: adipocyte-specific loss In Ucp1-Cre;Ctnnb1flox/flox mice, Ξ²-catenin loss in UCP1+ adipocytes promoted white-fat browning, increased thermogenic gene expression, and raised whole-body energy expenditure, indicating that Ctnnb1 restrains beige/thermogenic programs in this lineage. (chen2023ctnnb1Ξ²catenininactivationin pages 2-5, chen2023ctnnb1Ξ²catenininactivationin pages 5-8, chen2023ctnnb1Ξ²catenininactivationin pages 10-13, chen2023ctnnb1Ξ²catenininactivationin pages 18-20) UBKO mice showed more UCP1+ beige adipocytes, higher O2 consumption/energy expenditure, and improved later-life glucose metabolism; RNA-seq in eWAT found 290 upregulated and 1607 downregulated genes after CL-316,243 stimulation. (chen2023ctnnb1Ξ²catenininactivationin pages 5-8, chen2023ctnnb1Ξ²catenininactivationin pages 8-10) Chen et al., 2023, iScience, https://doi.org/10.1016/j.isci.2023.106552 (chen2023ctnnb1Ξ²catenininactivationin pages 2-5, chen2023ctnnb1Ξ²catenininactivationin pages 5-8, chen2023ctnnb1Ξ²catenininactivationin pages 10-13, chen2023ctnnb1Ξ²catenininactivationin pages 8-10, chen2023ctnnb1Ξ²catenininactivationin pages 18-20)

Table: This table summarizes the verified identity, domain structure, localization, core functions, regulation, and representative mouse-model evidence for mouse Ctnnb1/Ξ²-catenin. It is useful as a compact evidence map linking molecular annotation to recent in vivo studies and quantitative phenotypes.

Development/Application System/Model Key finding Quantitative data Implementation notes Source
Intestinal ieCtnnb1 enhancer dosage control Mouse intestinal epithelium; CRISPR/Cas9 deletion of upstream ieCtnnb1 enhancer to generate Ctnnb1Ξ”i.enh mice; crossed with ApcMin/+ for tumor studies A gut-specific enhancer upstream of Ctnnb1 tunes Ξ²-catenin dosage in crypts; enhancer loss lowers Ctnnb1 transcription, suppresses canonical Wnt output, alters crypt-cell composition, slows epithelial turnover, and strongly suppresses Wnt-driven intestinal tumorigenesis Ctnnb1 mRNA decreased 26.5% in small-intestinal crypts and 22.3% in large-intestinal crypts; nuclear Ξ²-catenin decreased 49.5% and cytosolic Ξ²-catenin 29.8%; Paneth-cell proportion decreased 49.2%; Ki67+ cells decreased 16.1% and EdU+ cells 21.9%; median survival in tumor model increased from 165 to 255 days CRISPR enhancer deletion, LacZ enhancer-reporter mice, scRNA-seq of crypt cells, RT-qPCR/RNA-seq, ApcMin/+ tumor model Hua et al., eLife, Sep 2024, https://doi.org/10.7554/elife.98238 (hua2024actnnb1enhancer pages 8-9, hua2024actnnb1enhancer pages 1-2, hua2024actnnb1enhancer pages 3-6, hua2024actnnb1enhancer pages 6-8, hua2024actnnb1enhancer pages 2-3)
ILC3 Ξ²-catenin activation and intestinal inflammation Mouse ILC3 lineage models including RorccreCtnnb1ex3fl/wt, CreERT2Ctnnb1ex3fl/wt, and Rag-deficient/chimera settings Constitutive or inducible Ξ²-catenin activation in ILC3s reduces ILC3 abundance and function, worsens colitis, and acts through a TCF-1/JunB/RORΞ³t regulatory axis with altered chromatin accessibility and reduced effector programs Inducible cultures yielded ~50% Ξ²-catenin+ ILC3s by day 6; study reports dramatic reduction in ILC3s, reduced Ki-67, impaired CFSE proliferation, decreased IL-22/IL-17A, and worsened DSS colitis, though most exact fold-changes are not stated in extracted text Cre/lox exon-3 stabilization allele, tamoxifen/4-OHT induction, CUT&Tag, ATAC-seq, luciferase reporters, siRNA against Junb/Nfatc2 Hao et al., Nature Communications, Apr 2024, https://doi.org/10.1038/s41467-024-45616-1 (hao2024dysregulationofwntΞ²catenin pages 1-2, hao2024dysregulationofwntΞ²catenin pages 7-8, hao2024dysregulationofwntΞ²catenin pages 8-9, hao2024dysregulationofwntΞ²catenin pages 5-7, hao2024dysregulationofwntΞ²catenin pages 11-12, hao2024dysregulationofwntΞ²catenin pages 4-5)
Ucp1-Cre adipocyte-specific Ctnnb1 knockout and WAT browning Ucp1-Cre;Ctnnb1flox/flox (UBKO) mice; cold exposure and CL-316,243 Ξ²3-adrenergic stimulation; adipocyte cultures Loss of Ξ²-catenin in UCP1+ adipocytes promotes beige-fat programming and whole-body energy expenditure, indicating Ctnnb1 restrains thermogenic WAT browning RNA-seq after CL-316,243 identified 290 upregulated and 1607 downregulated genes in eWAT; UBKO mice showed higher O2 consumption, CO2 production, and energy expenditure; long-term cohort sizes noted as n=25 controls and n=19 UBKO in metabolic analyses Cre/lox with Ucp1-Cre (JAX 024670), metabolic cages, cold challenge, CL-316,243 treatment, SVF-derived beige adipocyte assays, GEO dataset GSE227415 Chen et al., iScience, May 2023, https://doi.org/10.1016/j.isci.2023.106552 (chen2023ctnnb1Ξ²catenininactivationin pages 2-5, chen2023ctnnb1Ξ²catenininactivationin pages 5-8, chen2023ctnnb1Ξ²catenininactivationin pages 10-13, chen2023ctnnb1Ξ²catenininactivationin pages 8-10, chen2023ctnnb1Ξ²catenininactivationin pages 18-20)
RPE specification by separation-of-function Ctnnb1 alleles Mouse retinal pigment epithelium using Ctnnb1dm (transcription-impaired), Ctnnb1Y654E (reduced junction affinity), and constitutively active Ctnnb1Ξ”ex3 alleles During RPE specification, the transcriptional/Wnt role of Ξ²-catenin is more critical than its junctional role: transcription-impaired Ξ²-catenin cannot substitute for endogenous Ctnnb1, whereas a junction-weak allele can; excessive Ξ²-catenin activity redirects fate Primarily allele-based functional evidence rather than large quantitative metrics in extracted text; study concludes Wnt/Ξ²-catenin signaling is necessary for specification but not maintenance of mouse RPE Separation-of-function genetics in vivo, lineage-specific RPE manipulation, constitutively active exon-3 deletion allele Kim et al., Molecules and Cells, May 2023, https://doi.org/10.14348/molcells.2023.0029 (jongmyeong2023wntΞ²cateninsignalingpathway pages 1-2)
Chemical targeting via covalent degrader EN83 Mammalian cell systems including HiBiT-CTNNB1 HEK293 cells and colorectal cancer lines (HT29, COLO, SW480) EN83 directly and covalently modifies Ξ²-catenin, thermally destabilizes it, and promotes ubiquitin-proteasome-dependent degradation, demonstrating direct chemical tractability of CTNNB1 MS/MS mapped modification to C439, C466, C520, C619; mutational analysis showed C466, C520, C619 are functionally important for degradation; chemoproteomics found significant engagement of C619 and 139 other targets >50% among 8,251 quantified cysteines; active cellular concentrations included 10 Β΅M and 50 Β΅M in reported assays HiBiT screening, gel-based and isoDTB chemoproteomics, cysteine-mutant rescue, cellular thermal shift assay, proteasome and NEDDylation inhibitor rescue (bortezomib, MLN4924) Gowans et al., JACS, Jun 2024, https://doi.org/10.1021/jacs.4c05174 (gowans2024covalentdegraderof pages 1-4, gowans2024covalentdegraderof pages 4-7, gowans2024covalentdegraderof pages 14-19, gowans2024covalentdegraderof pages 7-10)

Table: This table summarizes major 2023–2024 mechanistic developments and practical applications involving mouse or mammalian Ctnnb1/Ξ²-catenin. It highlights experimental systems, quantitative outcomes, and implementation methods that are especially useful for functional annotation and translational context.

References

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Deep Research Report: Ctnnb1 (mouse)

(Ctnnb1-deep-research.md)

Deep Research Report: Ctnnb1 (mouse)

Generated using OpenAI Deep Research API

Ctnnb1 (Ξ²-Catenin) – Comprehensive Functional Profile

Gene Function and Molecular Mechanisms

Ctnnb1 encodes Ξ²-catenin, an 88 kDa protein that plays a dual role in cell adhesion and intracellular signaling (www.ncbi.nlm.nih.gov). In cell adhesion, Ξ²-catenin is a key cytoplasmic component of the cadherin-catenin complex at adherens junctions, linking the cytoplasmic tail of E-cadherin to Ξ±-catenin and the actin cytoskeleton (www.ncbi.nlm.nih.gov). This linkage is crucial for the adhesive function of classical cadherins in forming stable cell–cell contacts in epithelial and other tissues (www.ncbi.nlm.nih.gov). Ξ²-Catenin also serves as a central effector in the canonical Wnt signaling pathway, which controls cell proliferation, differentiation, and fate during development and tissue homeostasis (www.ncbi.nlm.nih.gov). In the absence of Wnt signal, free Ξ²-catenin (not bound at cell junctions) is rapidly targeted for destruction: it is phosphorylated on N-terminal serine/threonine residues by a β€œdestruction complex” consisting of AXIN, APC, casein kinase 1, and GSK3Ξ², followed by Ξ²-TrCP-mediated ubiquitination and proteasomal degradation (www.ncbi.nlm.nih.gov). However, when Wnt ligands are present, this destruction complex is inhibited, allowing Ξ²-catenin to stabilize and accumulate in the cytoplasm and eventually translocate into the nucleus (www.ncbi.nlm.nih.gov). In the nucleus, Ξ²-catenin acts as a co-activator for TCF/LEF transcription factors, forming a transcriptional complex that drives expression of Wnt target genes (www.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). Through these mechanisms, Ξ²-catenin links external Wnt signals to changes in gene expression, while also anchoring cell–cell adhesion complexes – a combination of functions that underscores its central role in signal transduction and cell structure (www.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov).

Cellular Localization and Subcellular Components

Ξ²-Catenin is predominantly found at the plasma membrane in cells, localized to adherens junctions (GO:0005912) where it complexes with cadherins and other catenins in the apicolateral and basolateral membrane regions of epithelial cells (www.informatics.jax.org). This membrane-associated pool of Ξ²-catenin is structural, contributing to cell junction assembly and maintenance. A significant portion of Ξ²-catenin also exists in the cytosol (GO:0005829), where it is either en route to degradation or poised for signaling. Cytosolic Ξ²-catenin participates in the Ξ²-catenin destruction complex (GO:1990907) (also referred to as the Axin-APC Wnt signalosome), a multi-protein complex that regulates Ξ²-catenin stability in the absence of Wnt signals (www.informatics.jax.org) (genular.atomic-lab.org). Upon Wnt pathway activation, stabilized Ξ²-catenin accumulates and translocates to the nucleus (GO:0005634) (www.ncbi.nlm.nih.gov). In the nucleus, Ξ²-catenin associates with chromatin (particularly euchromatin) as part of transcriptional complexes, co-activating gene expression programs (www.informatics.jax.org). Notably, Ξ²-catenin has been observed in specific subcellular structures: for example, it is a component of the Scribble-APC-Ξ²-catenin complex (implicated in cell polarity/signaling) and has been detected in neuronal synapses, including the postsynaptic density and synaptic membranes in hippocampal neurons (www.informatics.jax.org). This distribution reflects Ξ²-catenin’s ability to shuttle between the cell membrane, cytoplasm, and nucleus, acting in both structural cell adhesion contexts and gene regulatory contexts as needed.

Biological Processes Involvement

Ξ²-Catenin is involved in a wide array of biological processes, consistent with its structural and signaling functions. It is a pivotal mediator of the canonical Wnt signaling pathway (GO:0060070), driving cell fate specification and embryonic patterning. During embryogenesis, Ξ²-catenin is required for processes such as embryonic morphogenesis and axis specification, as initially shown by studies in model organisms where ectopic Ξ²-catenin can induce a secondary body axis (pubmed.ncbi.nlm.nih.gov). In organ development, Ξ²-catenin plays essential roles; for instance, it functions in nervous system development and the regulation of neurogenesis, as well as in the formation of organs like the kidney, lungs, and limbs (www.informatics.jax.org) (www.informatics.jax.org). At the cellular level, Ξ²-catenin is crucial for cell–cell adhesion (GO:0007155), working as part of adherens junctions that are necessary for maintaining epithelial layer integrity (www.proteinatlas.org). It also participates in the control of gene transcription by RNA polymerase II, reflecting its role as a transcriptional co-regulator in the nucleus (www.informatics.jax.org). Ξ²-Catenin activity influences processes like cell proliferation and differentiation, and it has been implicated in epithelial-to-mesenchymal transition (EMT), a process important in development and cancer metastasis (consistent with its Wnt signaling function). In the context of the nervous system, Ξ²-catenin contributes to synapse formation and plasticity; for example, it has been shown to affect synaptic signaling and neurotransmission in neuronal circuits (which may underlie some neurodevelopmental effects) (www.informatics.jax.org). Overall, Ctnnb1/Ξ²-catenin is annotated to numerous biological process terms, ranging from cell adhesion and signal transduction to tissue morphogenesis and regulation of cell cycle and apoptosis, highlighting its broad functional involvement (www.informatics.jax.org) (genular.atomic-lab.org).

Protein Domains and Structural Features

The Ξ²-catenin protein (781 amino acids in mouse) contains several defined regions that correspond to its functional domains. Its central portion (~~ residues 134–697) consists of a series of 12 tandem Armadillo repeats, a 42-amino-acid motif that classifies Ξ²-catenin as a member of the Armadillo repeat protein family (pubmed.ncbi.nlm.nih.gov). These Armadillo repeats fold together into a superhelical structure that forms a positively-charged groove, which serves as a versatile protein–protein interaction interface (pubmed.ncbi.nlm.nih.gov). Through this interface, Ξ²-catenin directly binds multiple partners, including the cytoplasmic tail of cadherins, TCF/LEF transcription factors, and the APC tumor suppressor protein (pubmed.ncbi.nlm.nih.gov). The N-terminal region of Ξ²-catenin contains several critical phosphorylation sites (Ser/Thr residues) that regulate its stability. In the absence of Wnt, these N-terminal residues (e.g. Ser33/37/Thr41 in human Ξ²-catenin) are phosphorylated by casein kinase 1 and GSK3Ξ², marking Ξ²-catenin for ubiquitin-mediated degradation (www.ncbi.nlm.nih.gov). This N-terminal β€œdegron” thus acts as a regulatory domain controlling Ξ²-catenin’s half-life. In contrast, the C-terminal region of Ξ²-catenin (approximately last 100 amino acids) is largely unstructured and is known as the transactivation domain. This C-terminal domain is necessary for Ξ²-catenin’s role in gene activation – it engages transcriptional co-activators and components of the basal transcription machinery. For example, experiments in Xenopus have shown that the C-terminal transactivation domain of Ξ²-catenin is required to drive Wnt target gene expression during axis formation (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). A fusion of Ξ²-catenin’s C-terminal domain to a DNA-binding protein can induce transcription and developmental effects, whereas Ξ²-catenin lacking the C-terminus cannot activate target genes effectively (pubmed.ncbi.nlm.nih.gov). Thus, structurally, Ξ²-catenin can be viewed as having a modular architecture: an N-terminal regulatory domain, a central Armadillo-repeat domain for protein interactions (scaffold for adhesion and signaling complexes), and a C-terminal domain for transcriptional activation. This architecture allows Ξ²-catenin to serve as both a scaffolding protein (at cell junctions and in multiprotein complexes) and a gene regulator, depending on context (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov).

Disease Associations and Phenotypes

Given its fundamental roles, it is not surprising that Ctnnb1/Ξ²-catenin is implicated in various diseases and developmental disorders. In humans, heterozygous loss-of-function mutations in CTNNB1 cause a rare autosomal dominant neurodevelopmental disorder (sometimes termed β€œCTNNB1 syndrome”), characterized by intellectual disability, spastic diplegia, and often congenital retinal dystrophy or exudative vitreoretinopathy due to impaired Wnt signaling in the eye (www.informatics.jax.org). Indeed, familial exudative vitreoretinopathy 7 (FEVR7) is caused by CTNNB1 mutations that disrupt Wnt-mediated vascular development in the retina (www.informatics.jax.org). Mouse models have been used to study autism spectrum disorder and other neuropsychiatric conditions, since alterations in Ξ²-catenin/ Wnt signaling or cell adhesion in the brain can lead to synaptic and behavioral defects (www.informatics.jax.org). On the other end of the spectrum, gain-of-function mutations in Ctnnb1 (especially those that stabilize Ξ²-catenin by preventing N-terminal phosphorylation) are oncogenic. Ξ²-Catenin is a well-known proto-oncogene: somatic CTNNB1 mutations or defects in its regulators (like APC) lead to excessive Wnt signaling, driving uncontrolled cell proliferation. Such activating mutations in CTNNB1 are found in a variety of cancers, notably colorectal cancer (CRC), hepatocellular carcinoma, medulloblastoma, ovarian cancer, and benign tumors like pilomatrixomas (www.informatics.jax.org) (www.proteinatlas.org). In fact, Ξ²-catenin’s involvement in colon cancer was first recognized through its binding to the APC protein, which is mutated in familial adenomatous polyposis coli – loss of APC leads to Ξ²-catenin accumulation and transcription of oncogenic Wnt targets (www.proteinatlas.org) (www.proteinatlas.org). Aside from cancer, tissue-specific Ctnnb1 mutations can cause developmental defects; for example, conditional deletion of Ctnnb1 in limb mesenchyme or other contexts results in failures of proper tissue development (due to loss of Wnt signaling in those cells). Germline knockout of Ctnnb1 in mice is embryonic lethal – embryos lacking Ξ²-catenin cannot complete pre-implantation development properly, partly because the blastomeres fail to remain adherent without Ξ²-catenin-mediated adhesion, causing embryo fragmentation (pubmed.ncbi.nlm.nih.gov). In chimeric or conditional settings, Ξ²-catenin–deficient embryos show severe gastrulation and patterning defects, underscoring its requirement in early embryonic cell fates. In summary, perturbations of Ξ²-catenin activity are associated with a spectrum of phenotypes: developmental disorders when Ξ²-catenin function is reduced, and oncogenesis when Ξ²-catenin function is hyperactive or unregulated.

Expression Patterns and Regulation

Ctnnb1 is expressed ubiquitously in the mouse, with particularly high expression in certain developing and adult tissues. During embryogenesis, Ξ²-catenin mRNA and protein are detected in many tissues, with notable levels in the central nervous system (e.g., embryonic brain) and in limb buds during mid-gestation (www.ncbi.nlm.nih.gov). As development progresses and in adult mice, Ctnnb1 continues to be broadly expressed. Ξ²-Catenin is highly expressed in self-renewing and progenitor cell populations – for instance, in the intestinal epithelium, which has a high turnover, Ξ²-catenin is expressed in crypt progenitor cells where Wnt signaling actively drives proliferation. A survey of CTNNB1 expression (human data, which parallels mouse) indicates it is widely expressed in multiple tissues and organs, with especially high levels observed in brain, uterus, lung, bladder, and kidney (pmc.ncbi.nlm.nih.gov). In the adult brain, Ξ²-catenin is enriched in regions like the cortex and hippocampus, consistent with its roles in synaptic function and neurogenesis (pmc.ncbi.nlm.nih.gov). The regulation of Ctnnb1 expression itself can be tissue-specific: recent studies have identified tissue-specific enhancers that modulate Ctnnb1 transcription in certain contexts (for example, an intestinal enhancer element that fine-tunes Ξ²-catenin levels to balance normal gut homeostasis versus tumorigenesis) (pmc.ncbi.nlm.nih.gov). Post-transcriptionally, the abundance of Ξ²-catenin protein in cells is chiefly regulated by the Wnt-dependent stabilization/degradation mechanism described earlier, rather than large changes in mRNA levels. Thus, while Ctnnb1 is constitutively expressed in most cell types (house-keeping role in adhesion), the activation state of Ξ²-catenin (and hence its function in signaling) is tightly controlled by upstream signals. Additionally, certain external factors and signaling pathways can influence Ξ²-catenin’s activity and localization – for instance, growth factors and hormones may modulate GSK3Ξ² activity or cadherin availability, indirectly affecting Ξ²-catenin. In summary, Ξ²-catenin is broadly and constitutively expressed in mammals, reflecting its fundamental role, and its activity is primarily regulated by protein stability and dynamic localization rather than on/off gene expression. This widespread expression pattern aligns with the diverse requirement for Ξ²-catenin in various cell types and organs throughout development and adulthood (www.informatics.jax.org) (pmc.ncbi.nlm.nih.gov).

Evolutionary Conservation

Ξ²-Catenin is highly conserved across metazoan species, underscoring its importance in essential cellular processes. The human CTNNB1 gene is orthologous to mouse Ctnnb1 with a high degree of sequence identity, and both encode Ξ²-catenin proteins with virtually identical domain structures (www.informatics.jax.org). Orthologs of Ξ²-catenin exist in all vertebrates and even in more distant animals. In Drosophila melanogaster, for example, the Ξ²-catenin homologue is called Armadillo (arm), which was originally discovered as a segment-polarity gene. Armadillo performs the same dual functions as vertebrate Ξ²-catenin: it is required for Wingless (Wnt) signaling and for assembly of adherens junctions in the fly (pubmed.ncbi.nlm.nih.gov). Studies in Drosophila have demonstrated that the molecular interactions are conserved – Armadillo binds to DE-cadherin and fly Ξ±-catenin for adhesion, and translocates to the nucleus to interact with Pangolin (fly TCF) for gene regulation (pubmed.ncbi.nlm.nih.gov). The conservation extends to the level of protein domains (the Armadillo repeat motifs are present in fly Armadillo and show high similarity to those in mouse Ξ²-catenin) and function. In Caenorhabditis elegans (nematode), the Ξ²-catenin functions are split between multiple paralogous proteins, due to an ancient gene duplication. C. elegans has at least two Ξ²-catenin-like proteins: HMP-2, which exclusively mediates cell–cell adhesion by partnering with the single worm cadherin (HMR-1), and BAR-1, which is dedicated to Wnt signaling, forming a complex with POP-1 (TCF) to activate Wnt target genes (pubmed.ncbi.nlm.nih.gov). This suggests that the ancestral Ξ²-catenin’s combined roles were partitioned in certain lineages (in worms and some insects) (pubmed.ncbi.nlm.nih.gov), whereas in vertebrates and fruit flies a single protein retains both functions. The core Wnt/Ξ²-catenin signaling pathway is thought to be ancient, as even primitive metazoans have Wnt ligands and Ξ²-catenin-like molecules to control developmental patterning. The cadherin–catenin cell adhesion complex is also an ancient invention of multicellular animals, indicating Ξ²-catenin has been a central player in multicellularity. Overall, the structure and function of Ξ²-catenin have been strongly conserved through evolution, from invertebrates to mammals, reflecting the essential and universal nature of Wnt signaling and cadherin-based adhesion in animal biology (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov).

Key Experimental Evidence and Literature

The functional understanding of Ξ²-catenin has been built through classic experiments in cell biology, developmental biology, and genetics. Early biochemical studies that co-immunoprecipitated E-cadherin complexes identified Ξ²-catenin (originally as an 88 kDa protein) as a cadherin-associated protein, linking cadherins to the cytoskeleton. This finding explained how cadherins, via catenins, transmit contact inhibition signals to stop cell division once an epithelial layer is confluent (www.proteinatlas.org). Genetic studies in Drosophila were pivotal: mutants in the armadillo gene were found to have disrupted segment development (due to failed Wingless signaling) and loss of epithelial integrity, highlighting both signaling and adhesion roles. A landmark Drosophila structure-function analysis used armadillo mutants to map Ξ²-catenin’s functional domains: it revealed that distinct regions of the protein mediate adhesion vs. Wnt signaling, and that these functions can be uncoupled (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). For example, the binding sites for DE-cadherin and Ξ±-catenin on Armadillo were mapped, and both interactions were shown to be required for adherens junction function (pubmed.ncbi.nlm.nih.gov). Separately, two regions crucial for Wingless/Wnt signaling were identified, and it was demonstrated that Armadillo protein accumulates in the nucleus to transmit the Wingless signal (pubmed.ncbi.nlm.nih.gov). These experiments provided direct evidence that Ξ²-catenin moves to the nucleus and that its roles in adhesion and signaling are molecularly separable (pubmed.ncbi.nlm.nih.gov). In vertebrates, a classic experiment in Xenopus laevis showed that microinjection of Ξ²-catenin mRNA into early embryos leads to the formation of a secondary body axis, effectively duplicating the embryonic organizer – a powerful demonstration that Ξ²-catenin activation is sufficient to induce major developmental programs (a hallmark of Wnt signaling) (pubmed.ncbi.nlm.nih.gov). Conversely, blockade of Ξ²-catenin (or its co-factor TCF) in embryos causes loss of dorsal structures, confirming its necessity in axis formation. In mouse models, Ctnnb1 knockout studies underscored the protein’s essential functions: embryos entirely lacking Ξ²-catenin arrest early in development. Notably, zygotic Ctnnb1 null embryos fail to complete blastocyst implantation, in part because their cells cannot adhere properly (blastomeres in Ξ²-catenin–deficient embryos tend to dissociate) (pubmed.ncbi.nlm.nih.gov). Conditional knockouts have further revealed tissue-specific requirements – for instance, deleting Ξ²-catenin in neural progenitors or in synaptic proteins has been shown to cause defects in synapse development and behavior, linking Ξ²-catenin to neurological phenotypes (e.g., autism-like behaviors in mice) (www.informatics.jax.org). In cancer biology, key evidence for Ξ²-catenin’s role came from the discovery of CTNNB1 mutations in tumors and from cell culture experiments: introducing stable, mutant Ξ²-catenin into normal cells drives them to adopt cancer-like traits, such as loss of contact inhibition and anchorage-independent growth. For example, one study showed that oncogenic Ξ²-catenin can block anoikis (detachment-induced cell death) in kidney and intestinal epithelial cells, promoting their survival and growth in suspension (www.proteinatlas.org). Structural biology has also contributed to our understanding: the crystal structure of Ξ²-catenin’s Armadillo repeat domain revealed how it forms a scaffold to accommodate various binding partners (pubmed.ncbi.nlm.nih.gov). This structural insight has guided the design of inhibitors that disrupt Ξ²-catenin’s interaction with TCF or other partners as potential therapeutic strategies in Wnt-driven cancers. Together, these experimental findings from diverse approaches provide a comprehensive picture of Ξ²-catenin as a protein that is indispensable for developmental processes and tissue architecture, and when dysregulated, a driver of disease.

Relevant Gene Ontology (GO) Terms

The multifaceted roles of Ctnnb1/Ξ²-catenin are captured by numerous Gene Ontology annotations, supported by experimental evidence in mouse and other species. Key GO terms associated with this gene include:

  • Molecular Function (MF):
  • Cadherin binding (GO:0045296) – Ξ²-catenin binds the cytoplasmic domain of cadherins at cell junctions (www.ncbi.nlm.nih.gov).
  • Alpha-catenin binding (GO:0034333) – interacts with Ξ±-catenin to link cadherin complexes to actin filaments (www.ncbi.nlm.nih.gov).
  • Transcription factor binding (GO:0008134) – binds TCF/LEF transcription factors in the nucleus to co-regulate gene expression (pubmed.ncbi.nlm.nih.gov).
  • Enzyme binding (GO:0019899) – associates with various enzymes (e.g., kinases like GSK3Ξ², or others in signaling complexes) (www.informatics.jax.org).

  • (Ξ²-Catenin has also been noted as a transcription co-activator, facilitating RNA polymerase II transcription, which corresponds to its role in transcription regulation.)

  • Biological Process (BP):

  • Canonical Wnt signaling pathway (GO:0060070) – mediates Wnt/Ξ²-catenin signal transduction leading to target gene activation (genular.atomic-lab.org).
  • Cell–cell adhesion (GO:0098609) – essential for adherens junction assembly and maintenance of tissue architecture (www.proteinatlas.org) (www.proteinatlas.org).
  • Regulation of transcription, DNA-templated (GO:0006355) – influences transcription of specific genes as part of the Ξ²-catenin/TCF complex (www.informatics.jax.org).
  • Neurogenesis (GO:0022008) – involved in nervous system development and generation of neurons (www.proteinatlas.org).
  • Embryonic morphogenesis (GO:0048598) – required for proper embryonic development and body plan formation (www.informatics.jax.org).
  • Epithelial to mesenchymal transition (GO:0001837) – participates in EMT during development and cancer progression (through Wnt signaling effects).

  • (Additional processes: Ξ²-catenin is also linked to cell proliferation, apoptosis regulation, stem cell maintenance, and axis specification as evidenced by various studies.)

  • Cellular Component (CC):

  • Adherens junction (GO:0005912) – localized at cadherin-based adherens junctions in the plasma membrane (www.proteinatlas.org).
  • Catenin complex (GO:0044338) – a component of the cadherin–catenin complex that mediates cell adhesion.
  • Cytosol (GO:0005829) – cytosolic pool where Ξ²-catenin is regulated by the destruction complex (genular.atomic-lab.org).
  • Nucleus (GO:0005634) – translocates to the nucleus to form transcriptional complexes on DNA (www.informatics.jax.org).
  • Ξ²-Catenin destruction complex (GO:1990907) – part of the Axin/APC/GSK3Ξ² complex that controls Ξ²-catenin stability (genular.atomic-lab.org).
  • Postsynaptic density (GO:0014069) – present at neuronal synapses, indicating a role in synaptic structure/function (www.informatics.jax.org).

Each of these GO terms is supported by experimental evidence (e.g., physical binding assays, localization studies, mutant phenotypes) from the literature. These annotations are useful for capturing the multi-functional nature of Ξ²-catenin in Gene Ontology, aiding curators and researchers in understanding the gene’s roles in a structured, searchable manner.

πŸ“š Additional Documentation

Notes

(Ctnnb1-notes.md)

Ctnnb1 Gene Review Notes

2025-01-14 - Major GOA Expansion Issue

Issue: Validation failure due to massive mismatch between review and current GOA file:
- 553 missing annotations from GOA
- 24 annotations not in GOA
- 190 new references needed

Root Cause: The Ctnnb1 GOA file has expanded dramatically from ~206 annotations to 816 lines since the original review. This represents one of the most significant updates in the dataset.

Action Taken: Used the GOA validator to seed all 553 missing annotations, which added 190 new references. However, this created a massive file (8099 lines) that may need manual curation.

Outstanding Issues:
1. Some annotations like GO:0019221 (cytokine-mediated signaling pathway) with PMID:19619491 appear to have been retired from GOA
2. The file now contains a mix of carefully reviewed annotations and newly seeded PENDING annotations
3. The validation is timing out due to the file size

Recommendation: This gene requires special attention in a future curation cycle to:
1. Review the 553 newly seeded annotations
2. Identify and mark retired annotations
3. Resolve evidence type mismatches
4. Streamline the review for better maintainability

Note: Beta-catenin is a highly studied protein involved in multiple pathways (Wnt signaling, cell adhesion, transcriptional regulation), which explains the extensive annotation expansion.

Bioreason Rl Predictions

(Ctnnb1-bioreason-rl-predictions.md)

BioReason Chat Export

Exported on March 22, 2026 at 01:25 AM

Organism: Mus musculus

Sequence:

MATQADLMELDMAMEPDRKAAVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTSQVLYEWEQGFSQSFTQEQVADIDGQYAMTRAQRVRAAMFPETLDEGMQIPSTQFDAAHPTNVQRLAEPSQMLKHAVVNLINYQDDAELATRAIPELTKLLNDEDQVVVNKAAVMVHQLSKKEASRHAIMRSPQMVSAIVRTMQNTNDVETARCTAGTLHNLSHHREGLLAIFKSGGIPALVKMLGSPVDSVLFYAITTLHNLLLHQEGAKMAVRLAGGLQKMVALLNKTNVKFLAITTDCLQILAYGNQESKLIILASGGPQALVNIMRTYTYEKLLWTTSRVLKVLSVCSSNKPAIVEAGGMQALGLHLTDPSQRLVQNCLWTLRNLSDAATKQEGMEGLLGTLVQLLGSDDINVVTCAAGILSNLTCNNYKNKMMVCQVGGIEALVRTVLRAGDREDITEPAICALRHLTSRHQEAEMAQNAVRLHYGLPVVVKLLHPPSHWPLIKATVGLIRNLALCPANHAPLREQGAIPRLVQLLVRAHQDTQRRTSMGGTQQQFVEGVRMEEIVEGCTGALHILARDVHNRIVIRGLNTIPLFVQLLYSPIENIQRVAAGVLCELAQDKEAAEAIEAEGATAPLTELLHSRNEGVATYAAAVLFRMSEDKPQDYKKRLSVELTSSLFRTEPMAWNETADLGLDIGAQGEALGYRQDDPSYRSFHSGGYGQDALGMDPMMEHEMGGHHPGADYPVDGLPDLGHAQDLMDGLPPGDSNQLAWFDTDL

Thinking Trace

I begin with the InterPro architecture. The sequence is assigned to IPR013284 (Beta-catenin family, residues 3–781), establishing membership in the beta-catenin/plakoglobin/plastin lineage that forms armadillo-repeat scaffolds. Nested within this, IPR011989 (Armadillo-like helical homologous superfamily, residues 123–666) and IPR016024 (Armadillo-type fold homologous superfamily, residues 135–664) define a central alpha-helical solenoid composed of tandem armadillo repeats. The repeat core is explicitly captured by IPR000225 (Armadillo repeat, residues 141–664). This ordered array of armadillo repeats creates an extended, positively charged groove that binds diverse partnersβ€”classically cadherin cytoplasmic tails and cateninsβ€”through multivalent, shape-complementary interactions. The N-terminal family signature and C-terminal tail together tune affinity and selectivity, causing robust protein–protein interaction capacity rather than catalysis.

This armadillo-repeat scaffold dictates molecular function as a binding hub. The repeat architecture generates high-affinity surfaces for assembling multiprotein complexes, supporting GO:0005515 protein binding as the primary molecular function. In beta-catenin family proteins, the same scaffold often coordinates junctional assemblies and transcriptional regulators; here, the absence of enzymatic motifs and the dominance of repeat-mediated interfaces argue that binding and scaffoldingβ€”not enzymatic activityβ€”are the core functions.

From function to process, the armadillo scaffold couples two major pathways. First, it nucleates adherens junctions by docking to cadherin cytoplasmic domains and recruiting other catenins, driving cell–cell adhesion and junction maturationβ€”central to adherens junction assembly and maintenance. Second, members of this family can shuttle to nuclear complexes and modulate transcriptional programs; although this isoform’s detailed roles are not fully resolved, the capacity of the armadillo core to assemble regulatory complexes rationalizes participation in signal-responsive gene control that coordinates with junctional signaling.

The cellular context follows directly from the scaffold’s role. The absence of transmembrane segments and the presence of extensive interaction surfaces predict a soluble cytoplasmic protein that concentrates at cell–cell junctions. This matches a junctional adaptor that operates at adherens junctions while remaining cytoplasmic when not bound, aligning with the observed cytoplasm/cytostroma and junctional enrichment.

Mechanistically, I hypothesize that this armadillo-repeat scaffold forms a high-avidity platform at adherens junctions, binding cadherin tails and recruiting alpha-catenin/plakophilins to stabilize the adhesion complex. Dynamic exchange with cytoplasmic pools likely allows regulated assembly with transcriptional co-regulators under signaling cues. Likely partners include classical cadherins and the catenin network at junctions, with transient associations to transcriptional regulators that tune adhesion-coupled gene expression.

Functional Summary

A cytoplasmic armadillo-repeat scaffold that concentrates at cell–cell junctions to organize multiprotein assemblies. By using a tandem helical repeat core, it binds cytoplasmic adhesion receptors and junctional adaptors to stabilize adherens junction architecture while dynamically exchanging with soluble pools. This binding-driven mechanism positions it to coordinate adhesion with signal-responsive gene regulation, operating predominantly at junctions within the cytoplasmic compartment.

UniProt Summary

Not yet known.

InterPro Domains

  • Beta-catenin (IPR013284, family) β€” residues 3-781
  • Armadillo-like helical (IPR011989, homologous_superfamily) β€” residues 123-666
  • Armadillo-type fold (IPR016024, homologous_superfamily) β€” residues 135-664
  • Armadillo (IPR000225, repeat) β€” residues 141-664

GO Terms

Molecular Function: molecular_function (GO:0003674), molecular function regulator activity (GO:0098772), binding (GO:0005488), transcription regulator activity (GO:0140110), molecular function activator activity (GO:0140677), heterocyclic compound binding (GO:1901363), chromatin binding (GO:0003682), organic cyclic compound binding (GO:0097159), transcription coregulator activity (GO:0003712), protein binding (GO:0005515), transcription factor binding (GO:0008134), nucleic acid binding (GO:0003676), alpha-catenin binding (GO:0045294), protein domain specific binding (GO:0019904), cell adhesion molecule binding (GO:0050839), enzyme binding (GO:0019899), transcription coactivator activity (GO:0003713), cadherin binding (GO:0045296), DNA-binding transcription factor binding (GO:0140297), kinase binding (GO:0019900), transcription coregulator binding (GO:0001221), disordered domain specific binding (GO:0097718), histone methyltransferase binding (GO:1990226), phosphatase binding (GO:0019902), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein kinase binding (GO:0019901), protein phosphatase binding (GO:0019903), nuclear receptor binding (GO:0016922)

Biological Process: biological_process (GO:0008150), biological regulation (GO:0065007), response to stimulus (GO:0050896), reproductive process (GO:0022414), regulation of biological process (GO:0050789), reproduction (GO:0000003), multicellular organismal process (GO:0032501), metabolic process (GO:0008152), homeostatic process (GO:0042592), immune system process (GO:0002376), localization (GO:0051179), signaling (GO:0023052), growth (GO:0040007), negative regulation of biological process (GO:0048519), positive regulation of biological process (GO:0048518), developmental process (GO:0032502), cellular process (GO:0009987), anatomical structure development (GO:0048856), negative regulation of signaling (GO:0023057), developmental process involved in reproduction (GO:0003006), multicellular organismal-level homeostasis (GO:0048871), anatomical structure formation involved in morphogenesis (GO:0048646), regulation of biological quality (GO:0065008), regulation of response to stimulus (GO:0048583), developmental maturation (GO:0021700), negative regulation of cellular process (GO:0048523), biosynthetic process (GO:0009058), establishment of localization (GO:0051234), macromolecule localization (GO:0033036), developmental growth (GO:0048589), leukocyte activation (GO:0045321), cell population proliferation (GO:0008283), nitrogen compound metabolic process (GO:0006807), negative regulation of multicellular organismal process (GO:0051241), cell death (GO:0008219), regulation of signaling (GO:0023051), negative regulation of developmental process (GO:0051093), signal transduction (GO:0007165), cell activation (GO:0001775), tissue remodeling (GO:0048771), immune system development (GO:0002520), developmental induction (GO:0031128), morphogenesis of a branching structure (GO:0001763), positive regulation of developmental process (GO:0051094), negative regulation of response to stimulus (GO:0048585), sexual reproduction (GO:0019953), cellular localization (GO:0051641), positive regulation of multicellular organismal process (GO:0051240), molting cycle (GO:0042303), pattern specification process (GO:0007389), cellular component organization or biogenesis (GO:0071840), regulation of multicellular organismal process (GO:0051239), negative regulation of metabolic process (GO:0009892), positive regulation of reproductive process (GO:2000243), cellular process involved in reproduction in multicellular organism (GO:0022412), regulation of cellular process (GO:0050794), cellular response to stimulus (GO:0051716), cellular developmental process (GO:0048869), organ growth (GO:0035265), regulation of metabolic process (GO:0019222), positive regulation of response to stimulus (GO:0048584), molting cycle process (GO:0022404), ossification (GO:0001503), regulation of molecular function (GO:0065009), cell communication (GO:0007154), positive regulation of cellular process (GO:0048522), anatomical structure morphogenesis (GO:0009653), cell motility (GO:0048870), regulation of reproductive process (GO:2000241), multicellular organism reproduction (GO:0032504), cell-cell signaling (GO:0007267), regulation of developmental process (GO:0050793), negative regulation of immune system process (GO:0002683), response to endogenous stimulus (GO:0009719), organelle localization (GO:0051640), positive regulation of signaling (GO:0023056), multicellular organism development (GO:0007275), cell adhesion (GO:0007155), regulation of immune system process (GO:0002682), organic substance metabolic process (GO:0071704), cellular metabolic process (GO:0044237), positive regulation of metabolic process (GO:0009893), multicellular organismal reproductive process (GO:0048609), primary metabolic process (GO:0044238), neural precursor cell proliferation (GO:0061351), hypothalamus development (GO:0021854), tube formation (GO:0035148), regulation of response to stress (GO:0080134), stem cell proliferation (GO:0072089), animal organ development (GO:0048513), regulation of hemopoiesis (GO:1903706), negative regulation of vasculature development (GO:1901343), negative regulation of hemopoiesis (GO:1903707), synaptic signaling (GO:0099536), regulation of anatomical structure morphogenesis (GO:0022603), negative regulation of cell cycle (GO:0045786), nephron development (GO:0072006), midbrain development (GO:0030901), positive regulation of nitrogen compound metabolic process (GO:0051173), positive regulation of cell differentiation (GO:0045597), appendage development (GO:0048736), germ cell development (GO:0007281), organic substance biosynthetic process (GO:1901576), animal organ formation (GO:0048645), cell-cell signaling by wnt (GO:0198738), positive regulation of muscle tissue development (GO:1901863), regulation of cellular response to stress (GO:0080135), hindbrain development (GO:0030902), cellular biosynthetic process (GO:0044249), macromolecule metabolic process (GO:0043170), positive regulation of biosynthetic process (GO:0009891), muscle structure development (GO:0061061), regulation of cell population proliferation (GO:0042127), regulation of cell death (GO:0010941), regionalization (GO:0003002), negative regulation of cell differentiation (GO:0045596), transport (GO:0006810), regulation of cellular metabolic process (GO:0031323), positive regulation of cell communication (GO:0010647), hair cycle process (GO:0022405), regulation of primary metabolic process (GO:0080090), ectodermal placode development (GO:0071696), negative regulation of signal transduction (GO:0009968), negative regulation of cell death (GO:0060548), cell differentiation (GO:0030154), negative regulation of nervous system development (GO:0051961), system development (GO:0048731), myoblast proliferation (GO:0051450), ectodermal placode formation (GO:0060788), regulation of leukocyte activation (GO:0002694), regulation of binding (GO:0051098), heart growth (GO:0060419), tube development (GO:0035295), cell morphogenesis (GO:0000902), regulation of cell cycle (GO:0051726), animal organ morphogenesis (GO:0009887), cell maturation (GO:0048469), regulation of myelination (GO:0031641), apoptotic signaling pathway (GO:0097190), pallium development (GO:0021543), cell surface receptor signaling pathway (GO:0007166), sex differentiation (GO:0007548), regulation of cellular component organization (GO:0051128), cranial skeletal system development (GO:1904888), cell-substrate adhesion (GO:0031589), positive regulation of cell population proliferation (GO:0008284), tube morphogenesis (GO:0035239), negative regulation of cell communication (GO:0010648), axis specification (GO:0009798), cell-cell adhesion (GO:0098609), hair follicle morphogenesis (GO:0031069), morphogenesis of a branching epithelium (GO:0061138), cardiac chamber development (GO:0003205), negative regulation of cellular metabolic process (GO:0031324), cell fate commitment (GO:0045165), cell fate determination (GO:0001709), embryonic morphogenesis (GO:0048598), lens development in camera-type eye (GO:0002088), tissue homeostasis (GO:0001894), hematopoietic or lymphoid organ development (GO:0048534), negative regulation of cartilage development (GO:0061037), hair cycle (GO:0042633), regulation of signal transduction (GO:0009966), foregut morphogenesis (GO:0007440), regulation of macromolecule metabolic process (GO:0060255), reproductive structure development (GO:0048608), cellular aromatic compound metabolic process (GO:0006725), vesicle localization (GO:0051648), positive regulation of epithelial to mesenchymal transition (GO:0010718), regulation of cellular component biogenesis (GO:0044087), establishment of organelle localization (GO:0051656), negative regulation of macromolecule metabolic process (GO:0010605), regulation of morphogenesis of a branching structure (GO:0060688), muscle cell proliferation (GO:0033002), embryo development (GO:0009790), regulation of cell cycle process (GO:0010564), regulation of cell activation (GO:0050865), nerve development (GO:0021675), regulation of catalytic activity (GO:0050790), negative regulation of nitrogen compound metabolic process (GO:0051172), cerebral cortex development (GO:0021987), positive regulation of molecular function (GO:0044093), positive regulation of macromolecule metabolic process (GO:0010604), blood vessel development (GO:0001568), telencephalon development (GO:0021537), heterocycle metabolic process (GO:0046483), establishment of localization in cell (GO:0051649), appendage morphogenesis (GO:0035107), cellular nitrogen compound metabolic process (GO:0034641), angiogenesis (GO:0001525), formation of primary germ layer (GO:0001704), regulation of multicellular organismal development (GO:2000026), diencephalon development (GO:0021536), positive regulation of cellular metabolic process (GO:0031325), bone remodeling (GO:0046849), regulation of DNA-binding transcription factor activity (GO:0051090), epithelial cell proliferation (GO:0050673), cellular macromolecule localization (GO:0070727), negative regulation of biosynthetic process (GO:0009890), male sex differentiation (GO:0046661), regulation of muscle tissue development (GO:1901861), regulation of cellular response to growth factor stimulus (GO:0090287), mesenchymal cell proliferation (GO:0010463), tissue morphogenesis (GO:0048729), programmed cell death (GO:0012501), cell development (GO:0048468), cardiac muscle tissue growth (GO:0055017), response to growth factor (GO:0070848), cell fate specification (GO:0001708), cellular response to endogenous stimulus (GO:0071495), regulation of synapse structure or activity (GO:0050803), lymphocyte activation (GO:0046649), anatomical structure maturation (GO:0071695), organic cyclic compound metabolic process (GO:1901360), genitalia morphogenesis (GO:0035112), lens morphogenesis in camera-type eye (GO:0002089), forebrain development (GO:0030900), regulation of nitrogen compound metabolic process (GO:0051171), hair follicle development (GO:0001942), nephron morphogenesis (GO:0072028), regulation of cell differentiation (GO:0045595), cellular component organization (GO:0016043), oocyte differentiation (GO:0009994), positive regulation of nervous system development (GO:0051962), cell migration (GO:0016477), positive regulation of animal organ morphogenesis (GO:0110110), positive regulation of signal transduction (GO:0009967), gamete generation (GO:0007276), intracellular signal transduction (GO:0035556), osteoblast differentiation (GO:0001649), cell surface receptor signaling pathway involved in cell-cell signaling (GO:1905114), positive regulation of cellular component organization (GO:0051130), embryonic pattern specification (GO:0009880), anatomical structure homeostasis (GO:0060249), tissue development (GO:0009888), nucleobase-containing compound metabolic process (GO:0006139), head development (GO:0060322), regulation of cell communication (GO:0010646), regulation of biosynthetic process (GO:0009889), cardiac chamber morphogenesis (GO:0003206), ectodermal placode morphogenesis (GO:0071697), positive regulation of morphogenesis of an epithelium (GO:1905332), endoderm development (GO:0007492), nephron epithelium development (GO:0072009), skeletal system morphogenesis (GO:0048705), regulation of synapse organization (GO:0050807), regulation of protein metabolic process (GO:0051246), cranial nerve development (GO:0021545), positive regulation of mesenchymal cell proliferation (GO:0002053), regulation of epithelial cell proliferation (GO:0050678), anterior/posterior axis specification (GO:0009948), cell-matrix adhesion (GO:0007160), synaptic vesicle cycle (GO:0099504), regulation of oxidative stress-induced cell death (GO:1903201), muscle cell differentiation (GO:0042692), neuron migration (GO:0001764), skeletal system development (GO:0001501), embryonic heart tube development (GO:0035050), cell surface receptor signaling pathway involved in heart development (GO:0061311), oocyte development (GO:0048599), circulatory system development (GO:0072359), regulation of response to oxidative stress (GO:1902882), forebrain cell migration (GO:0021885), cerebral cortex cell migration (GO:0021795), regulation of osteoblast differentiation (GO:0045667), regulation of cell proliferation involved in heart morphogenesis (GO:2000136), trachea development (GO:0060438), regulation of vasculature development (GO:1901342), positive regulation of epithelial cell differentiation (GO:0030858), response to fibroblast growth factor (GO:0071774), lung cell differentiation (GO:0060479), limb morphogenesis (GO:0035108), cell fate commitment involved in formation of primary germ layer (GO:0060795), epithelial tube formation (GO:0072175), positive regulation of macromolecule biosynthetic process (GO:0010557), chondrocyte differentiation (GO:0002062), positive regulation of histone methylation (GO:0031062), apoptotic process (GO:0006915), regulation of DNA binding (GO:0051101), I-kappaB kinase/NF-kappaB signaling (GO:0007249), regulation of nucleobase-containing compound metabolic process (GO:0019219), dorsal/ventral axis specification (GO:0009950), epithelium development (GO:0060429), positive regulation of organelle organization (GO:0010638), positive regulation of cellular biosynthetic process (GO:0031328), cellular response to growth factor stimulus (GO:0071363), regulation of animal organ formation (GO:0003156), regulation of epithelial cell differentiation (GO:0030856), respiratory system development (GO:0060541), regulation of mitotic cell cycle (GO:0007346), regulation of programmed cell death (GO:0043067), nephron epithelium morphogenesis (GO:0072088), gland development (GO:0048732), gastrulation (GO:0007369), cardiac ventricle development (GO:0003231), bone resorption (GO:0045453), morphogenesis of an epithelium (GO:0002009), positive regulation of neurogenesis (GO:0050769), skin development (GO:0043588), morphogenesis of embryonic epithelium (GO:0016331), coronary vasculature development (GO:0060976), branching morphogenesis of an epithelial tube (GO:0048754), cardiac ventricle morphogenesis (GO:0003208), regulation of myeloid cell differentiation (GO:0045637), embryonic organ development (GO:0048568), cell morphogenesis involved in differentiation (GO:0000904), renal tubule development (GO:0061326), regulation of skeletal muscle tissue development (GO:0048641), limbic system development (GO:0021761), negative regulation of myeloid cell differentiation (GO:0045638), nucleic acid metabolic process (GO:0090304), proximal/distal pattern formation (GO:0009954), branching involved in blood vessel morphogenesis (GO:0001569), regulation of chondrocyte differentiation (GO:0032330), negative regulation of cellular biosynthetic process (GO:0031327), negative regulation of Wnt signaling pathway (GO:0030178), regulation of animal organ morphogenesis (GO:2000027), negative regulation of nucleobase-containing compound metabolic process (GO:0045934), gene expression (GO:0010467), positive regulation of DNA-binding transcription factor activity (GO:0051091), renal system development (GO:0072001), glial cell fate commitment (GO:0021781), cardiac muscle cell proliferation (GO:0060038), neuroblast proliferation (GO:0007405), reproductive system development (GO:0061458), endoderm formation (GO:0001706), positive regulation of DNA metabolic process (GO:0051054), embryonic organ morphogenesis (GO:0048562), synaptic vesicle localization (GO:0097479), regulation of cell junction assembly (GO:1901888), positive regulation of cell development (GO:0010720), urogenital system development (GO:0001655), positive regulation of gene expression (GO:0010628), muscle organ morphogenesis (GO:0048644), regulation of mesenchymal cell proliferation (GO:0010464), negative regulation of oxidative stress-induced cell death (GO:1903202), regulation of apoptotic signaling pathway (GO:2001233), endodermal cell differentiation (GO:0035987), regulation of histone methylation (GO:0031060), positive regulation of binding (GO:0051099), positive regulation of nucleobase-containing compound metabolic process (GO:0045935), respiratory tube development (GO:0030323), prostate gland development (GO:0030850), glial cell migration (GO:0008347), trans-synaptic signaling (GO:0099537), negative regulation of macromolecule biosynthetic process (GO:0010558), cardiocyte differentiation (GO:0035051), regulation of epithelial to mesenchymal transition (GO:0010717), digestive tract development (GO:0048565), neuron differentiation (GO:0030182), cartilage development (GO:0051216), ganglion development (GO:0061548), epithelial tube morphogenesis (GO:0060562), embryonic digit morphogenesis (GO:0042733), regulation of macromolecule biosynthetic process (GO:0010556), sensory system development (GO:0048880), vasculature development (GO:0001944), connective tissue development (GO:0061448), glial cell differentiation (GO:0010001), telencephalon cell migration (GO:0022029), oviduct development (GO:0060066), establishment of vesicle localization (GO:0051650), kidney morphogenesis (GO:0060993), thymus development (GO:0048538), regulation of gene expression (GO:0010468), regulation of neural precursor cell proliferation (GO:2000177), regulation of cellular response to oxidative stress (GO:1900407), striated muscle cell proliferation (GO:0014855), regulation of embryonic development (GO:0045995), negative regulation of mitotic cell cycle (GO:0045930), synaptic vesicle transport (GO:0048489), positive regulation of intracellular signal transduction (GO:1902533), dorsal/ventral pattern formation (GO:0009953), mesonephric tubule development (GO:0072164), positive regulation of catalytic activity (GO:0043085), negative regulation of gene expression (GO:0010629), negative regulation of blood vessel morphogenesis (GO:2000181), heart development (GO:0007507), artery development (GO:0060840), autonomic nervous system development (GO:0048483), sympathetic nervous system development (GO:0048485), negative regulation of leukocyte differentiation (GO:1902106), leukocyte differentiation (GO:0002521), enzyme-linked receptor protein signaling pathway (GO:0007167), neuron fate commitment (GO:0048663), regulation of DNA metabolic process (GO:0051052), aromatic compound biosynthetic process (GO:0019438), regulation of cell development (GO:0060284), sensory organ development (GO:0007423), positive regulation of neural precursor cell proliferation (GO:2000179), genitalia development (GO:0048806), oogenesis (GO:0048477), regulation of neuron death (GO:1901214), negative regulation of apoptotic signaling pathway (GO:2001234), regulation of Wnt signaling pathway (GO:0030111), regulation of glial cell differentiation (GO:0045685), myeloid cell differentiation (GO:0030099), positive regulation of epithelial cell proliferation (GO:0050679), regulation of fibroblast growth factor receptor signaling pathway (GO:0040036), neurogenesis (GO:0022008), positive regulation of fibroblast growth factor receptor signaling pathway (GO:0045743), positive regulation of RNA metabolic process (GO:0051254), regulation of cartilage development (GO:0061035), trachea morphogenesis (GO:0060439), muscle tissue development (GO:0060537), regulation of cellular biosynthetic process (GO:0031326), regulation of stem cell proliferation (GO:0072091), embryonic axis specification (GO:0000578), regulation of organelle organization (GO:0033043), cellular nitrogen compound biosynthetic process (GO:0044271), positive regulation of stem cell proliferation (GO:2000648), embryonic appendage morphogenesis (GO:0035113), regulation of angiogenesis (GO:0045765), pancreas development (GO:0031016), protein localization (GO:0008104), regulation of transferase activity (GO:0051338), muscle organ development (GO:0007517), positive regulation of myoblast proliferation (GO:2000288), negative regulation of cell development (GO:0010721), cell junction organization (GO:0034330), embryo development ending in birth or egg hatching (GO:0009792), negative regulation of chondrocyte differentiation (GO:0032331), macromolecule biosynthetic process (GO:0009059), lung morphogenesis (GO:0060425), organic cyclic compound biosynthetic process (GO:1901362), digestive system development (GO:0055123), negative regulation of programmed cell death (GO:0043069), Wnt signaling pathway (GO:0016055), MAPK cascade (GO:0000165), odontogenesis (GO:0042476), sensory organ morphogenesis (GO:0090596), neuron fate determination (GO:0048664), positive regulation of osteoblast differentiation (GO:0045669), regulation of leukocyte proliferation (GO:0070663), lymphocyte differentiation (GO:0030098), brain development (GO:0007420), regulation of morphogenesis of an epithelium (GO:1905330), negative regulation of neurogenesis (GO:0050768), positive regulation of skeletal muscle tissue development (GO:0048643), nervous system development (GO:0007399), heart morphogenesis (GO:0003007), female gamete generation (GO:0007292), epidermis development (GO:0008544), heterocycle biosynthetic process (GO:0018130), vasculogenesis (GO:0001570), regulation of sister chromatid cohesion (GO:0007063), regulation of leukocyte differentiation (GO:1902105), central nervous system development (GO:0007417), ectoderm development (GO:0007398), regulation of RNA metabolic process (GO:0051252), regulation of lymphocyte activation (GO:0051249), negative regulation of angiogenesis (GO:0016525), hemopoiesis (GO:0030097), regulation of myoblast proliferation (GO:2000291), negative regulation of neuron death (GO:1901215), muscle tissue morphogenesis (GO:0060415), male genitalia development (GO:0030539), regulation of nervous system development (GO:0051960), mesenchyme development (GO:0060485), digestive tract morphogenesis (GO:0048546), epithelial cell differentiation (GO:0030855), nucleobase-containing compound biosynthetic process (GO:0034654), lung development (GO:0030324), stem cell differentiation (GO:0048863), mesenchyme morphogenesis (GO:0072132), blood vessel morphogenesis (GO:0048514), negative regulation of epithelial cell differentiation (GO:0030857), positive regulation of protein metabolic process (GO:0051247), T cell activation (GO:0042110), limb development (GO:0060173), vesicle-mediated transport (GO:0016192), negative regulation of RNA metabolic process (GO:0051253), kidney development (GO:0001822), regulation of intracellular signal transduction (GO:1902531), anterior/posterior pattern specification (GO:0009952), regulation of apoptotic process (GO:0042981), regulation of lymphocyte proliferation (GO:0050670), negative regulation of gliogenesis (GO:0014014), striated muscle tissue development (GO:0014706), mesonephros development (GO:0001823), regulation of mononuclear cell proliferation (GO:0032944), regulation of mitotic cell cycle, embryonic (GO:0009794), renal tubule morphogenesis (GO:0061333), regulation of histone H3-K4 methylation (GO:0051569), branching involved in ureteric bud morphogenesis (GO:0001658), regulation of oligodendrocyte differentiation (GO:0048713), positive regulation of RNA biosynthetic process (GO:1902680), tongue development (GO:0043586), artery morphogenesis (GO:0048844), negative regulation of myeloid leukocyte differentiation (GO:0002762), regulation of MAPK cascade (GO:0043408), positive regulation of transferase activity (GO:0051347), cardiac muscle tissue development (GO:0048738), kidney epithelium development (GO:0072073), positive regulation of histone H3-K4 methylation (GO:0051571), cranial ganglion development (GO:0061550), columnar/cuboidal epithelial cell differentiation (GO:0002065), gliogenesis (GO:0042063), neural plate development (GO:0001840), telencephalon glial cell migration (GO:0022030)

Cellular Component: cellular_component (GO:0005575), cellular anatomical entity (GO:0110165), protein-containing complex (GO:0032991), basal part of cell (GO:0045178), chromatin (GO:0000785), Z disc (GO:0030018), cell junction (GO:0030054), intracellular protein-containing complex (GO:0140535), postsynapse (GO:0098794), sarcomere (GO:0030017), extrinsic component of membrane (GO:0019898), I band (GO:0031674), transcription regulator complex (GO:0005667), membrane-enclosed lumen (GO:0031974), nucleoplasm (GO:0005654), supramolecular complex (GO:0099080), microtubule organizing center (GO:0005815), intracellular anatomical structure (GO:0005622), organelle (GO:0043226), cell projection (GO:0042995), lateral plasma membrane (GO:0016328), membrane (GO:0016020), cytosol (GO:0005829), presynapse (GO:0098793), cell periphery (GO:0071944), membrane protein complex (GO:0098796), cell leading edge (GO:0031252), apical part of cell (GO:0045177), Wnt signalosome (GO:1990909), presynaptic active zone (GO:0048786), catalytic complex (GO:1902494), cytoplasm (GO:0005737), nuclear protein-containing complex (GO:0140513), RNA polymerase II transcription repressor complex (GO:0090571), plasma membrane bounded cell projection (GO:0120025), intracellular organelle (GO:0043229), synapse (GO:0045202), cytoplasmic region (GO:0099568), plasma membrane protein complex (GO:0098797), anchoring junction (GO:0070161), membrane-bounded organelle (GO:0043227), plasma membrane (GO:0005886), postsynaptic specialization (GO:0099572), supramolecular polymer (GO:0099081), contractile fiber (GO:0043292), extrinsic component of plasma membrane (GO:0019897), euchromatin (GO:0000791), transcription repressor complex (GO:0017053), cell cortex (GO:0005938), lamellipodium (GO:0030027), RNA polymerase II transcription regulator complex (GO:0090575), non-membrane-bounded organelle (GO:0043228), centrosome (GO:0005813), postsynaptic membrane (GO:0045211), presynaptic membrane (GO:0042734), basal plasma membrane (GO:0009925), plasma membrane region (GO:0098590), organelle lumen (GO:0043233), membrane microdomain (GO:0098857), presynaptic active zone cytoplasmic component (GO:0098831), beta-catenin destruction complex (GO:0030877), apicolateral plasma membrane (GO:0016327), membrane raft (GO:0045121), Schaffer collateral - CA1 synapse (GO:0098685), cell projection membrane (GO:0031253), catenin complex (GO:0016342), intracellular non-membrane-bounded organelle (GO:0043232), postsynaptic density (GO:0014069), glutamatergic synapse (GO:0098978), beta-catenin-TCF complex (GO:1990907), neuron to neuron synapse (GO:0098984), supramolecular fiber (GO:0099512), myofibril (GO:0030016), plasma membrane raft (GO:0044853), intracellular organelle lumen (GO:0070013), actin-based cell projection (GO:0098858), synaptic membrane (GO:0097060), intracellular membrane-bounded organelle (GO:0043231), postsynaptic specialization, intracellular component (GO:0099091), basolateral plasma membrane (GO:0016323), cell-cell junction (GO:0005911), cell cortex region (GO:0099738), apical junction complex (GO:0043296), asymmetric synapse (GO:0032279), cytoskeleton (GO:0005856), cell-cell contact zone (GO:0044291), chromosome (GO:0005694), microvillus (GO:0005902), caveola (GO:0005901), postsynaptic density, intracellular component (GO:0099092), nucleus (GO:0005634), nuclear lumen (GO:0031981), tight junction (GO:0070160), adherens junction (GO:0005912), microvillus membrane (GO:0031528), bicellular tight junction (GO:0005923), microtubule cytoskeleton (GO:0015630), intercalated disc (GO:0014704)

Generated by BioReason

Bioreason Rl Review

(Ctnnb1-bioreason-rl-review.md)

BioReason-Pro RL Review: Ctnnb1 (mouse)

Source: Ctnnb1-bioreason-rl-predictions.md

  • Correctness: 4/5
  • Completeness: 3/5

Functional Summary Review

The BioReason functional summary captures the structural basis well but is incomplete on function:

A cytoplasmic armadillo-repeat scaffold that concentrates at cell-cell junctions to organize multiprotein assemblies. By using a tandem helical repeat core, it binds cytoplasmic adhesion receptors and junctional adaptors to stabilize adherens junction architecture while dynamically exchanging with soluble pools. This binding-driven mechanism positions it to coordinate adhesion with signal-responsive gene regulation, operating predominantly at junctions within the cytoplasmic compartment.

The adhesion role is correctly identified -- the curated review confirms beta-catenin "links cadherins to the actin cytoskeleton at adherens junctions to mediate cell-cell adhesion" (GO:0045296, cadherin binding; GO:0098609, cell-cell adhesion; GO:0005912, adherens junction). However, the summary significantly underweights the Wnt signaling / transcriptional co-activator function.

The curated review describes Ctnnb1 as having "dual roles in cell adhesion and Wnt signaling" and devotes equal emphasis to its nuclear function: "stabilized beta-catenin translocates to the nucleus where it acts as a transcriptional co-activator with TCF/LEF transcription factors." The BioReason summary only vaguely alludes to this as "signal-responsive gene regulation" without naming Wnt signaling, TCF/LEF, or the nuclear translocation. This is a major omission since the Wnt/beta-catenin transcriptional axis is arguably as important as the adhesion role.

The thinking trace hedges with "although this isoform's detailed roles are not fully resolved," which is incorrect -- Ctnnb1's role in Wnt signaling is extremely well-characterized in mouse. This appears to be a limitation of relying purely on domain architecture without literature context.

Comparison with interpro2go:

There are no GO_REF:0000002 annotations for Ctnnb1 in the curated review. BioReason's GO term predictions do include many Wnt-related terms (GO:0016055 Wnt signaling pathway, GO:0198738 cell-cell signaling by wnt) and transcriptional terms, suggesting the GO prediction module captures what the functional summary misses. This disconnect between the narrative summary and the predicted GO terms is notable -- the summary is more conservative than the GO predictions.

Notes on thinking trace

The trace correctly identifies the armadillo-repeat scaffold and cadherin-binding groove. However, it explicitly hedges on the transcriptional role ("this isoform's detailed roles are not fully resolved"), which is a significant error of caution -- Ctnnb1/beta-catenin's transcriptional co-activator function is one of the most studied signaling mechanisms in developmental biology.

πŸ“„ View Raw YAML

 
id: Q02248
gene_symbol: Ctnnb1
product_type: PROTEIN
status: COMPLETE
description: 'Beta-catenin is a multifunctional Armadillo-repeat protein with two conserved core roles: at adherens junctions it binds classical cadherins and alpha-catenin to support cadherin-mediated cell-cell adhesion, and in canonical Wnt signaling it accumulates in the nucleus and acts as a transcriptional coactivator with TCF/LEF-family DNA-binding transcription factors. These molecular roles explain the many developmental, proliferative, differentiation, and tissue-patterning phenotypes in mouse; those organismal processes are generally downstream context-specific consequences rather than separate core molecular functions.'
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
existing_annotations:
- term:
    id: GO:0001525
    label: angiogenesis
  evidence_type: IMP
  original_reference_id: PMID:28463231
  review:
    summary: Beta-catenin promotes angiogenesis via endothelial Wnt/TCF transcription and adherens-junction integrity; a vascular developmental consequence, not a core function.
    action: KEEP_AS_NON_CORE
    reason: downstream vascular outcome of Wnt and junction roles
    supported_by:
    - reference_id: PMID:28463231
      supporting_text: Disruption of lineage specification in adult pulmonary mesenchymal progenitor cells promotes microvascular dysfunction.
- term:
    id: GO:0001708
    label: cell fate specification
  evidence_type: IMP
  original_reference_id: PMID:28463231
  review:
    summary: Beta-catenin specifies cell fates via context-dependent Wnt target activation; a developmental specification outcome, not a proximal molecular mechanism.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven fate specification
    supported_by:
    - reference_id: PMID:28463231
      supporting_text: Disruption of lineage specification in adult pulmonary mesenchymal progenitor cells promotes microvascular dysfunction.
- term:
    id: GO:0019221
    label: cytokine-mediated signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:19619491
  review:
    summary: Beta-catenin intersects cytokine-responsive transcription via Wnt crosstalk in development/immunity; an indirect signaling outcome rather than a direct cytokine-pathway role.
    action: KEEP_AS_NON_CORE
    reason: indirect crosstalk; downgrade from UNDECIDED to non-core
    supported_by:
    - reference_id: PMID:19619491
      supporting_text: Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
  retired: true
- term:
    id: GO:0002064
    label: epithelial cell development
  evidence_type: IMP
  original_reference_id: PMID:16102745
  review:
    summary: Beta-catenin supports epithelial cell development via junction-mediated polarity and Wnt transcription; an epithelial differentiation outcome downstream of its dual role.
    action: KEEP_AS_NON_CORE
    reason: downstream of junction/Wnt epithelial roles
    supported_by:
    - reference_id: PMID:16102745
      supporting_text: 'The duality of beta-catenin function: a requirement in lens morphogenesis and signaling suppression of lens fate in periocular ectoderm.'
  retired: true
- term:
    id: GO:0001944
    label: vasculature development
  evidence_type: IMP
  original_reference_id: PMID:25083995
  review:
    summary: Whole-vasculature development depends on beta-catenin Wnt signaling in endothelium; a broad downstream organ-system phenotype.
    action: KEEP_AS_NON_CORE
    reason: System-level vascular development downstream of Wnt/beta-catenin output.
    supported_by:
    - reference_id: PMID:25083995
      supporting_text: Canonical WNT signaling components in vascular development and barrier formation.
- term:
    id: GO:0010467
    label: gene expression
  evidence_type: IMP
  original_reference_id: PMID:25083995
  review:
    summary: The broad 'gene expression' parent is uninformative; beta-catenin's specific role is coactivation of TCF/LEF target gene transcription by Pol II.
    action: MARK_AS_OVER_ANNOTATED
    reason: Overly broad parent superseded by specific Pol II transcription terms.
    supported_by:
    - reference_id: PMID:25083995
      supporting_text: Canonical WNT signaling components in vascular development and barrier formation.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:16040629
  review:
    summary: An IDA call; beta-catenin represses certain Pol II targets in specific contexts, but this should be downgraded relative to its core activating coactivator role, not removed.
    action: KEEP_AS_NON_CORE
    reason: Experimental (IDA); downgrade context-specific repression, do not REMOVE.
    supported_by:
    - reference_id: PMID:16040629
      supporting_text: Beta-catenin regulates differentiation of respiratory epithelial cells in vivo.
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: IGI
  original_reference_id: PMID:16478791
  review:
    summary: IGI evidence links beta-catenin to MAPK signaling, but this is signaling crosstalk and not a core function of the Wnt effector.
    action: KEEP_AS_NON_CORE
    reason: Crosstalk pathway, not the gene's central Wnt/transcription function.
    supported_by:
    - reference_id: PMID:16478791
      supporting_text: APC inhibits ERK pathway activation and cellular proliferation induced by RAS.
  retired: true
- term:
    id: GO:0000578
    label: embryonic axis specification
  evidence_type: IDA
  original_reference_id: PMID:9230313
  review:
    summary: Beta-catenin establishes the primary embryonic axis (organizer formation) via nuclear Wnt/TCF activation (IDA); a hallmark downstream developmental outcome of its signaling role.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven embryonic axis formation
    supported_by:
    - reference_id: PMID:9230313
      supporting_text: The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.
- term:
    id: GO:0000902
    label: cell morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:16102745
  review:
    summary: Beta-catenin shapes cell morphology via adherens-junction cytoskeletal linkage and Wnt transcription; a morphogenetic outcome of its dual structural/signaling roles.
    action: KEEP_AS_NON_CORE
    reason: downstream of junction and Wnt roles
    supported_by:
    - reference_id: PMID:16102745
      supporting_text: 'The duality of beta-catenin function: a requirement in lens morphogenesis and signaling suppression of lens fate in periocular ectoderm.'
- term:
    id: GO:0001501
    label: skeletal system development
  evidence_type: IMP
  original_reference_id: PMID:15866163
  review:
    summary: Beta-catenin Wnt signaling shapes skeletal patterning and ossification broadly; a high-level downstream organ-system phenotype.
    action: KEEP_AS_NON_CORE
    reason: System-level skeletal development downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:15866163
      supporting_text: Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
- term:
    id: GO:0001569
    label: branching involved in blood vessel morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:12975353
  review:
    summary: Endothelial beta-catenin drives vessel branching through Wnt/TCF transcription and junction remodeling; a vascular morphogenetic outcome downstream of its dual role.
    action: KEEP_AS_NON_CORE
    reason: downstream vascular branching from Wnt/junction roles
    supported_by:
    - reference_id: PMID:12975353
      supporting_text: The conditional inactivation of the beta-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility.
- term:
    id: GO:0001569
    label: branching involved in blood vessel morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:19154719
  review:
    summary: Endothelial beta-catenin drives vessel branching through Wnt/TCF transcription and junction remodeling; a vascular morphogenetic outcome downstream of its dual role.
    action: KEEP_AS_NON_CORE
    reason: downstream vascular branching from Wnt/junction roles
    supported_by:
    - reference_id: PMID:19154719
      supporting_text: Nrarp coordinates endothelial Notch and Wnt signaling to control vessel density in angiogenesis.
- term:
    id: GO:0001570
    label: vasculogenesis
  evidence_type: IMP
  original_reference_id: PMID:18231602
  review:
    summary: De novo vessel formation requires Wnt/beta-catenin transcriptional control of endothelial precursors; a downstream developmental process.
    action: KEEP_AS_NON_CORE
    reason: Vasculogenesis downstream of Wnt-driven endothelial transcription.
    supported_by:
    - reference_id: PMID:18231602
      supporting_text: Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
- term:
    id: GO:0001649
    label: osteoblast differentiation
  evidence_type: IMP
  original_reference_id: PMID:15866163
  review:
    summary: Wnt/beta-catenin is a master driver of osteoblast fate via Runx2/Osterix-linked targets; the differentiation outcome is downstream of that transcription.
    action: KEEP_AS_NON_CORE
    reason: Osteoblastogenesis downstream of Wnt/beta-catenin transcriptional program.
    supported_by:
    - reference_id: PMID:15866163
      supporting_text: Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
  retired: true
- term:
    id: GO:0001658
    label: branching involved in ureteric bud morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:17537789
  review:
    summary: Beta-catenin Wnt signaling drives ureteric bud branching in kidney development; a renal morphogenetic outcome downstream of TCF target activation.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven renal branching morphogenesis
    supported_by:
    - reference_id: PMID:17537789
      supporting_text: Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development.
- term:
    id: GO:0001701
    label: in utero embryonic development
  evidence_type: IMP
  original_reference_id: PMID:18231602
  review:
    summary: Beta-catenin is essential for embryonic viability/development in utero via Wnt signaling and adhesion (IGI/IMP); a broad developmental outcome of its dual role, not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream of Wnt/junction roles in embryogenesis
    supported_by:
    - reference_id: PMID:18231602
      supporting_text: Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
- term:
    id: GO:0001701
    label: in utero embryonic development
  evidence_type: IGI
  original_reference_id: PMID:19204372
  review:
    summary: Beta-catenin is essential for embryonic viability/development in utero via Wnt signaling and adhesion (IGI/IMP); a broad developmental outcome of its dual role, not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream of Wnt/junction roles in embryogenesis
    supported_by:
    - reference_id: PMID:19204372
      supporting_text: Both the RGS domain and the six C-terminal amino acids of mouse Axin are required for normal embryogenesis.
- term:
    id: GO:0001702
    label: gastrulation with mouth forming second
  evidence_type: IMP
  original_reference_id: PMID:8582267
  review:
    summary: Beta-catenin drives deuterostome gastrulation/germ-layer movements via Wnt-driven organizer transcription; an early morphogenetic outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven gastrulation
    supported_by:
    - reference_id: PMID:8582267
      supporting_text: Lack of beta-catenin affects mouse development at gastrulation.
- term:
    id: GO:0001706
    label: endoderm formation
  evidence_type: IMP
  original_reference_id: PMID:12194849
  review:
    summary: Beta-catenin promotes definitive endoderm formation through nuclear Wnt/TCF activation; a germ-layer developmental outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven endoderm formation
    supported_by:
    - reference_id: PMID:12194849
      supporting_text: Formation of multiple hearts in mice following deletion of beta-catenin in the embryonic endoderm.
- term:
    id: GO:0001706
    label: endoderm formation
  evidence_type: IMP
  original_reference_id: PMID:23824574
  review:
    summary: Beta-catenin promotes definitive endoderm formation through nuclear Wnt/TCF activation; a germ-layer developmental outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven endoderm formation
    supported_by:
    - reference_id: PMID:23824574
      supporting_text: Wnt/Ξ²-catenin signalling regulates Sox17 expression and is essential for organizer and endoderm formation in the mouse.
- term:
    id: GO:0001708
    label: cell fate specification
  evidence_type: IMP
  original_reference_id: PMID:15866163
  review:
    summary: Beta-catenin specifies cell fates via context-dependent Wnt target activation; a developmental specification outcome, not a proximal molecular mechanism.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven fate specification
    supported_by:
    - reference_id: PMID:15866163
      supporting_text: Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
- term:
    id: GO:0001711
    label: endodermal cell fate commitment
  evidence_type: IMP
  original_reference_id: PMID:12194849
  review:
    summary: Beta-catenin commits cells to endodermal fate via Wnt target-gene activation; a cell-fate outcome downstream of its transcriptional effector role.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven endoderm commitment
    supported_by:
    - reference_id: PMID:12194849
      supporting_text: Formation of multiple hearts in mice following deletion of beta-catenin in the embryonic endoderm.
- term:
    id: GO:0001764
    label: neuron migration
  evidence_type: IGI
  original_reference_id: PMID:21937711
  review:
    summary: Beta-catenin affects neuronal migration through combined cadherin-adhesion and Wnt-transcriptional roles; a downstream CNS phenotype (genetic interaction).
    action: KEEP_AS_NON_CORE
    reason: Neuron migration downstream of adhesion plus Wnt transcription.
    supported_by:
    - reference_id: PMID:21937711
      supporting_text: ASPM regulates Wnt signaling pathway activity in the developing brain.
- term:
    id: GO:0001822
    label: kidney development
  evidence_type: IMP
  original_reference_id: PMID:17537789
  review:
    summary: Beta-catenin drives nephrogenesis and tubule patterning via Wnt/TCF transcription; a renal organ-development outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven kidney development
    supported_by:
    - reference_id: PMID:17537789
      supporting_text: Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development.
- term:
    id: GO:0001840
    label: neural plate development
  evidence_type: IDA
  original_reference_id: PMID:22102609
  review:
    summary: Beta-catenin patterns the early neural plate through Wnt-dependent anteroposterior transcriptional control; an IDA developmental phenotype downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: Neural plate patterning downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:22102609
      supporting_text: Increased Ξ²-catenin activity in the anterior neural plate induces ectopic mid-hindbrain characteristics.
- term:
    id: GO:0001894
    label: tissue homeostasis
  evidence_type: IMP
  original_reference_id: PMID:18635608
  review:
    summary: Beta-catenin Wnt signaling maintains adult tissue homeostasis (e.g. gut crypt renewal); a broad downstream organismal phenotype.
    action: KEEP_AS_NON_CORE
    reason: Tissue homeostasis downstream of Wnt/beta-catenin self-renewal transcription.
    supported_by:
    - reference_id: PMID:18635608
      supporting_text: Tissue-specific requirements of beta-catenin in external genitalia development.
- term:
    id: GO:0001944
    label: vasculature development
  evidence_type: IMP
  original_reference_id: PMID:19129494
  review:
    summary: Whole-vasculature development depends on beta-catenin Wnt signaling in endothelium; a broad downstream organ-system phenotype.
    action: KEEP_AS_NON_CORE
    reason: System-level vascular development downstream of Wnt/beta-catenin output.
    supported_by:
    - reference_id: PMID:19129494
      supporting_text: Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis.
- term:
    id: GO:0002052
    label: positive regulation of neuroblast proliferation
  evidence_type: IGI
  original_reference_id: PMID:21937711
  review:
    summary: Beta-catenin positively drives neuroblast expansion through Wnt cell-cycle targets; a downstream neurodevelopmental proliferative role.
    action: KEEP_AS_NON_CORE
    reason: Pro-neuroblast proliferation downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:21937711
      supporting_text: ASPM regulates Wnt signaling pathway activity in the developing brain.
- term:
    id: GO:0002053
    label: positive regulation of mesenchymal cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:18231602
  review:
    summary: Beta-catenin expands mesenchymal cells via Wnt mitogenic targets during organogenesis; a downstream proliferative phenotype.
    action: KEEP_AS_NON_CORE
    reason: Mesenchymal proliferation downstream of Wnt mitogenic transcription.
    supported_by:
    - reference_id: PMID:18231602
      supporting_text: Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
- term:
    id: GO:0002053
    label: positive regulation of mesenchymal cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:18533146
  review:
    summary: Beta-catenin expands mesenchymal cells via Wnt mitogenic targets during organogenesis; a downstream proliferative phenotype.
    action: KEEP_AS_NON_CORE
    reason: Mesenchymal proliferation downstream of Wnt mitogenic transcription.
    supported_by:
    - reference_id: PMID:18533146
      supporting_text: An FGF-WNT gene regulatory network controls lung mesenchyme development.
- term:
    id: GO:0002062
    label: chondrocyte differentiation
  evidence_type: IMP
  original_reference_id: PMID:15866163
  review:
    summary: Beta-catenin gates chondrocyte vs osteoblast fate via Wnt/TCF transcription; a skeletal cell-fate outcome downstream of its signaling effector role.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven chondrocyte fate
    supported_by:
    - reference_id: PMID:15866163
      supporting_text: Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
  retired: true
- term:
    id: GO:0002062
    label: chondrocyte differentiation
  evidence_type: IGI
  original_reference_id: PMID:16818445
  review:
    summary: Beta-catenin gates chondrocyte vs osteoblast fate via Wnt/TCF transcription; a skeletal cell-fate outcome downstream of its signaling effector role.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven chondrocyte fate
    supported_by:
    - reference_id: PMID:16818445
      supporting_text: Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis.
  retired: true
- term:
    id: GO:0002089
    label: lens morphogenesis in camera-type eye
  evidence_type: IMP
  original_reference_id: PMID:16102745
  review:
    summary: Beta-catenin (tightly regulated) shapes lens morphogenesis via Wnt transcription and epithelial junctions; an ocular morphogenetic outcome of its dual role.
    action: KEEP_AS_NON_CORE
    reason: downstream of Wnt/junction roles in lens
    supported_by:
    - reference_id: PMID:16102745
      supporting_text: 'The duality of beta-catenin function: a requirement in lens morphogenesis and signaling suppression of lens fate in periocular ectoderm.'
- term:
    id: GO:0003266
    label: regulation of secondary heart field cardioblast proliferation
  evidence_type: IDA
  original_reference_id: PMID:19620969
  review:
    summary: Beta-catenin controls cardioblast proliferation in the second heart field via Wnt mitogenic targets; an IDA downstream cardiac phenotype.
    action: KEEP_AS_NON_CORE
    reason: SHF cardioblast proliferation downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:19620969
      supporting_text: A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate.
- term:
    id: GO:0003338
    label: metanephros morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:19060336
  review:
    summary: Beta-catenin shapes metanephric kidney morphogenesis via Wnt/TCF transcription; a renal morphogenetic outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven metanephros morphogenesis
    supported_by:
    - reference_id: PMID:19060336
      supporting_text: A Wnt7b-dependent pathway regulates the orientation of epithelial cell division and establishes the cortico-medullary axis of the mammalian kidney.
- term:
    id: GO:0003340
    label: negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis
  evidence_type: IDA
  original_reference_id: PMID:17537789
  review:
    summary: In kidney development beta-catenin tunes MET during nephrogenesis via Wnt-target transcription; the IDA is a specific developmental phenotype, not the proximal activity.
    action: KEEP_AS_NON_CORE
    reason: Specific kidney MET-regulation phenotype downstream of beta-catenin Wnt transcriptional control of nephron epithelialization.
    supported_by:
    - reference_id: PMID:17537789
      supporting_text: Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development.
- term:
    id: GO:0006351
    label: DNA-templated transcription
  evidence_type: IMP
  original_reference_id: PMID:15866163
  review:
    summary: beta-catenin is not part of the basal transcription machinery; it is a TCF/LEF coactivator. The bare 'DNA-templated transcription' parent is uninformative relative to its specific Pol II coactivator role.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic transcription parent; its real role is captured by transcription coactivator / positive regulation of Pol II transcription.
    supported_by:
    - reference_id: PMID:15866163
      supporting_text: Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
  retired: true
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:12235125
  review:
    summary: Essence correct but the directionless parent under-specifies beta-catenin's role; it functions specifically as a POSITIVE regulator/coactivator of Pol II transcription.
    action: MODIFY
    reason: Generic regulation parent; specialize to positive regulation of Pol II transcription.
    proposed_replacement_terms: &id001
    - id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    supported_by:
    - reference_id: PMID:12235125
      supporting_text: Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor.
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:12464179
  review:
    summary: Essence correct but the directionless parent under-specifies beta-catenin's role; it functions specifically as a POSITIVE regulator/coactivator of Pol II transcription.
    action: MODIFY
    reason: Generic regulation parent; specialize to positive regulation of Pol II transcription.
    proposed_replacement_terms: *id001
    supported_by:
    - reference_id: PMID:12464179
      supporting_text: Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:20043884
  review:
    summary: Essence correct but the directionless parent under-specifies beta-catenin's role; it functions specifically as a POSITIVE regulator/coactivator of Pol II transcription.
    action: MODIFY
    reason: Generic regulation parent; specialize to positive regulation of Pol II transcription.
    proposed_replacement_terms: *id001
    supported_by:
    - reference_id: PMID:20043884
      supporting_text: Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling within the Apical Ectodermal Ridge (AER) regulates interdigit formation.
- term:
    id: GO:0006366
    label: transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:15907834
  review:
    summary: beta-catenin is not a component of the Pol II transcription apparatus; this bare process term over-annotates its specific coactivator function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative process term; coactivator/positive-regulation terms preferred.
    supported_by:
    - reference_id: PMID:15907834
      supporting_text: Wnt/beta-catenin signaling acts upstream of N-myc, BMP4, and FGF signaling to regulate proximal-distal patterning in the lung.
  retired: true
- term:
    id: GO:0007160
    label: cell-matrix adhesion
  evidence_type: IMP
  original_reference_id: PMID:15131783
  review:
    summary: Cell-matrix adhesion is not a recognized beta-catenin function (it acts at cell-cell, not cell-ECM, junctions); the IMP basis cannot be verified here.
    action: UNDECIDED
    reason: Likely indirect/mislabeled, but IMP experimental annotation β€” do not REMOVE; flag for review.
    supported_by:
    - reference_id: PMID:15131783
      supporting_text: 'Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin.'
- term:
    id: GO:0007249
    label: canonical NF-kappaB signal transduction
  evidence_type: IMP
  original_reference_id: PMID:19619491
  review:
    summary: An IMP annotation; beta-catenin has documented crosstalk with NF-kappaB, but this is not its core function and the experimental call should be downgraded, not removed.
    action: KEEP_AS_NON_CORE
    reason: Experimental (IMP) crosstalk annotation; downgrade rather than REMOVE.
    supported_by:
    - reference_id: PMID:19619491
      supporting_text: Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
  retired: true
- term:
    id: GO:0007268
    label: chemical synaptic transmission
  evidence_type: IMP
  original_reference_id: PMID:14622577
  review:
    summary: Beta-catenin contributes to synaptic structure/vesicle organization at junctions affecting transmission; a neuronal outcome downstream of its adhesion role.
    action: KEEP_AS_NON_CORE
    reason: downstream of synaptic adhesion organization
    supported_by:
    - reference_id: PMID:14622577
      supporting_text: Role of beta-catenin in synaptic vesicle localization and presynaptic assembly.
- term:
    id: GO:0007398
    label: ectoderm development
  evidence_type: IMP
  original_reference_id: PMID:8582267
  review:
    summary: Beta-catenin guides ectodermal development through Wnt-driven fate and morphogenesis; a germ-layer developmental outcome downstream of its transcriptional role.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven ectoderm development
    supported_by:
    - reference_id: PMID:8582267
      supporting_text: Lack of beta-catenin affects mouse development at gastrulation.
- term:
    id: GO:0007403
    label: glial cell fate determination
  evidence_type: IDA
  original_reference_id: PMID:17706960
  review:
    summary: Beta-catenin biases neural progenitors toward glial fate via Wnt/TCF transcription (IDA); a CNS cell-fate outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven glial fate determination
    supported_by:
    - reference_id: PMID:17706960
      supporting_text: Persistent expression of stabilized beta-catenin delays maturation of radial glial cells into intermediate progenitors.
- term:
    id: GO:0007405
    label: neuroblast proliferation
  evidence_type: IGI
  original_reference_id: PMID:21937711
  review:
    summary: Beta-catenin expands neuroblasts via Wnt mitogenic targets in genetic-interaction assays; a downstream CNS proliferative phenotype.
    action: KEEP_AS_NON_CORE
    reason: Neuroblast proliferation downstream of Wnt mitogenic transcription.
    supported_by:
    - reference_id: PMID:21937711
      supporting_text: ASPM regulates Wnt signaling pathway activity in the developing brain.
  retired: true
- term:
    id: GO:0007507
    label: heart development
  evidence_type: IMP
  original_reference_id: PMID:12464179
  review:
    summary: Beta-catenin contributes broadly to cardiac development through Wnt-driven progenitor programs and junctions; an organ-development outcome of its dual role, not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt/junction-driven heart development
    supported_by:
    - reference_id: PMID:12464179
      supporting_text: Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.
- term:
    id: GO:0008104
    label: intracellular protein localization
  evidence_type: IMP
  original_reference_id: PMID:16621792
  review:
    summary: Beta-catenin contributes to localizing partner proteins (e.g. junctional/synaptic cargo), a secondary process distinct from its own core roles.
    action: KEEP_AS_NON_CORE
    reason: Peripheral process; IMP.
    supported_by:
    - reference_id: PMID:16621792
      supporting_text: 'Membrane localization of adenomatous polyposis coli protein at cellular protrusions: targeting sequences and regulation by beta-catenin.'
- term:
    id: GO:0008283
    label: cell population proliferation
  evidence_type: IMP
  original_reference_id: PMID:19690384
  review:
    summary: Generic proliferation umbrella conveying nothing beta-catenin-specific; specific tissue-proliferation terms already capture Wnt-driven growth roles.
    action: MARK_AS_OVER_ANNOTATED
    reason: vague proliferation umbrella adds no specificity
    supported_by:
    - reference_id: PMID:19690384
      supporting_text: Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.
  retired: true
- term:
    id: GO:0008283
    label: cell population proliferation
  evidence_type: IMP
  original_reference_id: PMID:15131783
  review:
    summary: Generic proliferation umbrella conveying nothing beta-catenin-specific; specific tissue-proliferation terms already capture Wnt-driven growth roles.
    action: MARK_AS_OVER_ANNOTATED
    reason: vague proliferation umbrella adds no specificity
    supported_by:
    - reference_id: PMID:15131783
      supporting_text: 'Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin.'
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IMP
  original_reference_id: PMID:19690384
  review:
    summary: Beta-catenin drives proliferation via Wnt mitogenic targets (Myc, cyclin D1); a key but downstream consequence of its transcriptional coactivation.
    action: KEEP_AS_NON_CORE
    reason: Proliferation downstream of Wnt target genes Myc/CcnD1; non-core.
    supported_by:
    - reference_id: PMID:19690384
      supporting_text: Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.
- term:
    id: GO:0008543
    label: fibroblast growth factor receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:18533146
  review:
    summary: Beta-catenin intersects FGFR signaling indirectly through Wnt/FGF developmental crosstalk; an experimental (IMP) phenotype downstream of signaling integration, not a core FGFR-pathway role.
    action: KEEP_AS_NON_CORE
    reason: experimental; indirect FGF/Wnt crosstalk, downgrade not remove
    supported_by:
    - reference_id: PMID:18533146
      supporting_text: An FGF-WNT gene regulatory network controls lung mesenchyme development.
  retired: true
- term:
    id: GO:0009948
    label: anterior/posterior axis specification
  evidence_type: IMP
  original_reference_id: PMID:10662781
  review:
    summary: Beta-catenin patterns the A/P axis through nuclear Wnt/TCF target activation in early embryo; an axial patterning outcome downstream of its transcriptional effector role.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven axial patterning
    supported_by:
    - reference_id: PMID:10662781
      supporting_text: Requirement for beta-catenin in anterior-posterior axis formation in mice.
- term:
    id: GO:0009950
    label: dorsal/ventral axis specification
  evidence_type: IMP
  original_reference_id: PMID:12923052
  review:
    summary: Beta-catenin contributes to D/V axial specification through nuclear Wnt target activation; an axial patterning outcome downstream of its effector role.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven D/V axis specification
    supported_by:
    - reference_id: PMID:12923052
      supporting_text: Genetic interaction between Wnt/beta-catenin and BMP receptor signaling during formation of the AER and the dorsal-ventral axis in the limb.
- term:
    id: GO:0009953
    label: dorsal/ventral pattern formation
  evidence_type: IMP
  original_reference_id: PMID:15708565
  review:
    summary: Beta-catenin participates in D/V pattern formation via Wnt/TCF transcriptional readout; a tissue-patterning outcome, not a proximal mechanism.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven D/V patterning
    supported_by:
    - reference_id: PMID:15708565
      supporting_text: Effects of canonical Wnt signaling on dorso-ventral specification of the mouse telencephalon.
- term:
    id: GO:0009954
    label: proximal/distal pattern formation
  evidence_type: IMP
  original_reference_id: PMID:12885771
  review:
    summary: Beta-catenin Wnt signaling contributes to proximodistal patterning (e.g. limb/organ axes) via target-gene gradients; a downstream patterning phenotype.
    action: KEEP_AS_NON_CORE
    reason: P/D patterning downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:12885771
      supporting_text: beta-Catenin is required for specification of proximal/distal cell fate during lung morphogenesis.
- term:
    id: GO:0010463
    label: mesenchymal cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:18231602
  review:
    summary: Beta-catenin promotes mesenchymal proliferation via Wnt target-gene activation; a connective-tissue growth outcome downstream of its transcriptional role.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven mesenchymal proliferation
    supported_by:
    - reference_id: PMID:18231602
      supporting_text: Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
  retired: true
- term:
    id: GO:0010463
    label: mesenchymal cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:18533146
  review:
    summary: Beta-catenin promotes mesenchymal proliferation via Wnt target-gene activation; a connective-tissue growth outcome downstream of its transcriptional role.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven mesenchymal proliferation
    supported_by:
    - reference_id: PMID:18533146
      supporting_text: An FGF-WNT gene regulatory network controls lung mesenchyme development.
  retired: true
- term:
    id: GO:0010468
    label: regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:22102609
  review:
    summary: Very broad regulatory parent; beta-catenin's specific role is TCF/LEF coactivation regulating Pol II transcription of Wnt targets.
    action: MARK_AS_OVER_ANNOTATED
    reason: Top-level generic parent; specific Pol II coactivation terms preferred.
    supported_by:
    - reference_id: PMID:22102609
      supporting_text: Increased Ξ²-catenin activity in the anterior neural plate induces ectopic mid-hindbrain characteristics.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:18231602
  review:
    summary: Broad parent; beta-catenin's specific activating role is coactivation of TCF/LEF target gene transcription by Pol II, captured by more precise terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative broad parent superseded by Pol II coactivation terms.
    supported_by:
    - reference_id: PMID:18231602
      supporting_text: Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:19690384
  review:
    summary: Broad parent; beta-catenin's specific activating role is coactivation of TCF/LEF target gene transcription by Pol II, captured by more precise terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative broad parent superseded by Pol II coactivation terms.
    supported_by:
    - reference_id: PMID:19690384
      supporting_text: Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.
- term:
    id: GO:0010718
    label: positive regulation of epithelial to mesenchymal transition
  evidence_type: ISO
  original_reference_id: GO_REF:0000008
  review:
    summary: Nuclear beta-catenin drives EMT transcriptional programs (Snail/Twist targets) while loss of its junctional pool also promotes EMT; the process is downstream of both core roles.
    action: KEEP_AS_NON_CORE
    reason: EMT is a transcriptional/adhesion downstream output, not beta-catenin's direct molecular function.
- term:
    id: GO:0016331
    label: morphogenesis of embryonic epithelium
  evidence_type: IMP
  original_reference_id: PMID:16102745
  review:
    summary: Embryonic epithelial shaping requires Wnt/beta-catenin transcriptional output plus cadherin-junction adhesion, but the morphogenetic outcome is downstream of those proximal roles.
    action: KEEP_AS_NON_CORE
    reason: Downstream tissue morphogenesis driven by beta-catenin's Wnt-transcription and adhesion roles, not a molecular function.
    supported_by:
    - reference_id: PMID:16102745
      supporting_text: 'The duality of beta-catenin function: a requirement in lens morphogenesis and signaling suppression of lens fate in periocular ectoderm.'
- term:
    id: GO:0021819
    label: layer formation in cerebral cortex
  evidence_type: IMP
  original_reference_id: PMID:20503375
  review:
    summary: Beta-catenin influences cortical layering through Wnt/adhesion-dependent neural development, a tissue-specific developmental output.
    action: KEEP_AS_NON_CORE
    reason: Developmental neuronal role; IMP, non-core.
    supported_by:
    - reference_id: PMID:20503375
      supporting_text: Expression analysis of an evolutionarily conserved metallophosphodiesterase gene, Mpped1, in the normal and beta-catenin-deficient malformed dorsal telencephalon.
- term:
    id: GO:0022009
    label: central nervous system vasculogenesis
  evidence_type: IMP
  original_reference_id: PMID:19023080
  review:
    summary: Beta-catenin drives CNS vessel formation through endothelial Wnt/TCF transcription; a neurovascular developmental outcome, not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven CNS vasculogenesis
    supported_by:
    - reference_id: PMID:19023080
      supporting_text: Canonical Wnt signaling regulates organ-specific assembly and differentiation of CNS vasculature.
- term:
    id: GO:0022405
    label: hair cycle process
  evidence_type: IMP
  original_reference_id: PMID:11371349
  review:
    summary: Beta-catenin drives hair-follicle cycling (anagen entry) via Wnt/TCF transcription in follicle stem cells; a skin-appendage outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven hair cycling
    supported_by:
    - reference_id: PMID:11371349
      supporting_text: beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin.
- term:
    id: GO:0030097
    label: hemopoiesis
  evidence_type: IDA
  original_reference_id: PMID:12717450
  review:
    summary: Beta-catenin modulates hematopoietic stem/progenitor activity via Wnt/TCF transcription (IDA); a blood-lineage developmental outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven hematopoiesis
    supported_by:
    - reference_id: PMID:12717450
      supporting_text: A role for Wnt signalling in self-renewal of haematopoietic stem cells.
- term:
    id: GO:0030154
    label: cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:16102745
  review:
    summary: Top-level differentiation umbrella that says nothing specific about beta-catenin; its specific lineage-differentiation terms already capture the Wnt-driven roles.
    action: MARK_AS_OVER_ANNOTATED
    reason: vague umbrella superseded by specific terms
    supported_by:
    - reference_id: PMID:16102745
      supporting_text: 'The duality of beta-catenin function: a requirement in lens morphogenesis and signaling suppression of lens fate in periocular ectoderm.'
  retired: true
- term:
    id: GO:0030217
    label: T cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:14608382
  review:
    summary: Beta-catenin modulates thymocyte/T-cell differentiation through Wnt/TCF target-gene activation; an immune-lineage developmental outcome, not its proximal adhesion or transcriptional mechanism.
    action: KEEP_AS_NON_CORE
    reason: downstream of Wnt/TCF program in lymphoid lineage
    supported_by:
    - reference_id: PMID:14608382
      supporting_text: Deletion of beta-catenin impairs T cell development.
- term:
    id: GO:0030316
    label: osteoclast differentiation
  evidence_type: IMP
  original_reference_id: PMID:15866165
  review:
    summary: Beta-catenin indirectly shapes osteoclast differentiation through osteoblast-derived RANKL/OPG balance; a downstream bone phenotype.
    action: KEEP_AS_NON_CORE
    reason: Osteoclast differentiation downstream of Wnt-controlled RANKL/OPG output.
    supported_by:
    - reference_id: PMID:15866165
      supporting_text: Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
- term:
    id: GO:0030324
    label: lung development
  evidence_type: IMP
  original_reference_id: PMID:12885771
  review:
    summary: Beta-catenin governs lung branching and cell-fate programs through Wnt transcription; a respiratory organ-development outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven lung development
    supported_by:
    - reference_id: PMID:12885771
      supporting_text: beta-Catenin is required for specification of proximal/distal cell fate during lung morphogenesis.
- term:
    id: GO:0048709
    label: oligodendrocyte differentiation
  evidence_type: IMP
  original_reference_id: PMID:19503085
  review:
    summary: Beta-catenin Wnt signaling modulates oligodendrocyte lineage progression; the differentiation process is downstream of its transcription.
    action: KEEP_AS_NON_CORE
    reason: Glial differentiation downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:19503085
      supporting_text: HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction.
  retired: true
- term:
    id: GO:0051450
    label: myoblast proliferation
  evidence_type: IMP
  original_reference_id: PMID:18231602
  review:
    summary: Wnt/beta-catenin signaling promotes myoblast expansion during myogenesis; this proliferative phenotype is a downstream consequence of its transcriptional output.
    action: KEEP_AS_NON_CORE
    reason: Myogenic proliferation downstream of beta-catenin Wnt-target transcription.
    supported_by:
    - reference_id: PMID:18231602
      supporting_text: Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
  retired: true
- term:
    id: GO:0060441
    label: epithelial tube branching involved in lung morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:18533146
  review:
    summary: Beta-catenin drives lung airway branching through Wnt-driven epithelial-mesenchymal programs; a pulmonary morphogenetic outcome, not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven lung branching
    supported_by:
    - reference_id: PMID:18533146
      supporting_text: An FGF-WNT gene regulatory network controls lung mesenchyme development.
  retired: true
- term:
    id: GO:0060487
    label: lung epithelial cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:16040629
  review:
    summary: Beta-catenin specifies lung epithelial cell types via Wnt/TCF transcription; an airway cell-fate outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven lung epithelial fate
    supported_by:
    - reference_id: PMID:16040629
      supporting_text: Beta-catenin regulates differentiation of respiratory epithelial cells in vivo.
  retired: true
- term:
    id: GO:0060767
    label: epithelial cell proliferation involved in prostate gland development
  evidence_type: IMP
  original_reference_id: PMID:12813461
  review:
    summary: Beta-catenin promotes prostate epithelial proliferation via Wnt target genes; a tissue-specific growth outcome downstream of its transcriptional role.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven prostate epithelial proliferation
    supported_by:
    - reference_id: PMID:12813461
      supporting_text: Activation of beta-catenin in prostate epithelium induces hyperplasias and squamous transdifferentiation.
  retired: true
- term:
    id: GO:0072089
    label: stem cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:18533146
  review:
    summary: Beta-catenin Wnt signaling sustains stem/progenitor self-renewal and proliferation across tissues; a key downstream consequence of its transcriptional program.
    action: KEEP_AS_NON_CORE
    reason: Stem-cell proliferation/maintenance downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:18533146
      supporting_text: An FGF-WNT gene regulatory network controls lung mesenchyme development.
  retired: true
- term:
    id: GO:0097190
    label: apoptotic signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:15131783
  review:
    summary: Beta-catenin influences apoptotic signaling indirectly via Wnt target genes (e.g. survival genes); a cell-fate consequence, not a direct apoptotic mechanism.
    action: KEEP_AS_NON_CORE
    reason: indirect, downstream of Wnt survival-gene program
    supported_by:
    - reference_id: PMID:15131783
      supporting_text: 'Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin.'
  retired: true
- term:
    id: GO:0097190
    label: apoptotic signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:20454446
  review:
    summary: Beta-catenin influences apoptotic signaling indirectly via Wnt target genes (e.g. survival genes); a cell-fate consequence, not a direct apoptotic mechanism.
    action: KEEP_AS_NON_CORE
    reason: indirect, downstream of Wnt survival-gene program
    supported_by:
    - reference_id: PMID:20454446
      supporting_text: WNT4/beta-catenin pathway maintains female germ cell survival by inhibiting activin betaB in the mouse fetal ovary.
  retired: true
- term:
    id: GO:0097190
    label: apoptotic signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:20454446
  review:
    summary: Beta-catenin influences apoptotic signaling indirectly via Wnt target genes (e.g. survival genes); a cell-fate consequence, not a direct apoptotic mechanism.
    action: KEEP_AS_NON_CORE
    reason: indirect, downstream of Wnt survival-gene program
    supported_by:
    - reference_id: PMID:20454446
      supporting_text: WNT4/beta-catenin pathway maintains female germ cell survival by inhibiting activin betaB in the mouse fetal ovary.
  retired: true
- term:
    id: GO:0032212
    label: positive regulation of telomere maintenance via telomerase
  evidence_type: IMP
  original_reference_id: PMID:22723415
  review:
    summary: Beta-catenin up-regulates Tert transcription, boosting telomerase activity; a downstream transcriptional-target effect rather than a direct enzymatic role.
    action: KEEP_AS_NON_CORE
    reason: Telomerase upregulation downstream of beta-catenin Tert transcription.
    supported_by:
    - reference_id: PMID:22723415
      supporting_text: Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
- term:
    id: GO:0001222
    label: transcription corepressor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Binding to corepressors (e.g. via ICAT/Groucho crosstalk) modulates Wnt output, a regulatory rather than core coactivation interaction.
    action: KEEP_AS_NON_CORE
    reason: Regulatory partner; electronic, non-core.
- term:
    id: GO:0016358
    label: dendrite development
  evidence_type: IGI
  original_reference_id: PMID:27713508
  review:
    summary: Beta-catenin influences dendrite development through synaptic/adhesion roles in neurons, a tissue-specific developmental process.
    action: KEEP_AS_NON_CORE
    reason: Neuronal developmental role; IGI, non-core.
    supported_by:
    - reference_id: PMID:27713508
      supporting_text: Conditional Knockout of Breast Carcinoma Amplified Sequence 2 (BCAS2) in Mouse Forebrain Causes Dendritic Malformation via Ξ²-catenin.
- term:
    id: GO:0001222
    label: transcription corepressor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Binding to corepressors (e.g. via ICAT/Groucho crosstalk) modulates Wnt output, a regulatory rather than core coactivation interaction.
    action: KEEP_AS_NON_CORE
    reason: Regulatory partner; electronic, non-core.
- term:
    id: GO:0060856
    label: establishment of blood-brain barrier
  evidence_type: IMP
  original_reference_id: PMID:25083995
  review:
    summary: Beta-catenin (Wnt7-driven) establishes BBB endothelial properties via TCF transcription and junctions; a neurovascular barrier outcome downstream of its dual role.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt/junction-driven BBB formation
    supported_by:
    - reference_id: PMID:25083995
      supporting_text: Canonical WNT signaling components in vascular development and barrier formation.
- term:
    id: GO:1990963
    label: establishment of blood-retinal barrier
  evidence_type: IMP
  original_reference_id: PMID:25083995
  review:
    summary: Beta-catenin (Norrin/Wnt-driven) establishes the blood-retinal barrier via TCF transcription and junctional integrity; a barrier-formation outcome downstream of its dual role.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt/junction-driven BRB formation
    supported_by:
    - reference_id: PMID:25083995
      supporting_text: Canonical WNT signaling components in vascular development and barrier formation.
- term:
    id: GO:0001709
    label: cell fate determination
  evidence_type: IMP
  original_reference_id: PMID:15708565
  review:
    summary: Beta-catenin biases cell-fate determination by activating Wnt/TCF lineage genes; a developmental fate outcome downstream of its transcriptional role.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven fate determination
    supported_by:
    - reference_id: PMID:15708565
      supporting_text: Effects of canonical Wnt signaling on dorso-ventral specification of the mouse telencephalon.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:15024079
  review:
    summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
    action: ACCEPT
    reason: Core nuclear Wnt role; IDA/IGI-supported.
    supported_by:
    - reference_id: PMID:15024079
      supporting_text: Brn-2 expression controls melanoma proliferation and is directly regulated by beta-catenin.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:15778706
  review:
    summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
    action: ACCEPT
    reason: Core nuclear Wnt role; IDA/IGI-supported.
    supported_by:
    - reference_id: PMID:15778706
      supporting_text: Wnt signalling induces maturation of Paneth cells in intestinal crypts.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:15907834
  review:
    summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
    action: ACCEPT
    reason: Core nuclear Wnt role; IDA/IGI-supported.
    supported_by:
    - reference_id: PMID:15907834
      supporting_text: Wnt/beta-catenin signaling acts upstream of N-myc, BMP4, and FGF signaling to regulate proximal-distal patterning in the lung.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:16581771
  review:
    summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
    action: ACCEPT
    reason: Core nuclear Wnt role; IDA/IGI-supported.
    supported_by:
    - reference_id: PMID:16581771
      supporting_text: CCN1/Cyr61 is regulated by the canonical Wnt signal and plays an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells.
- term:
    id: GO:0030154
    label: cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:15131783
  review:
    summary: Top-level differentiation umbrella that says nothing specific about beta-catenin; its specific lineage-differentiation terms already capture the Wnt-driven roles.
    action: MARK_AS_OVER_ANNOTATED
    reason: vague umbrella superseded by specific terms
    supported_by:
    - reference_id: PMID:15131783
      supporting_text: 'Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin.'
- term:
    id: GO:0030154
    label: cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:16192304
  review:
    summary: Top-level differentiation umbrella that says nothing specific about beta-catenin; its specific lineage-differentiation terms already capture the Wnt-driven roles.
    action: MARK_AS_OVER_ANNOTATED
    reason: vague umbrella superseded by specific terms
    supported_by:
    - reference_id: PMID:16192304
      supporting_text: Beta-catenin is essential for pancreatic acinar but not islet development.
- term:
    id: GO:0030324
    label: lung development
  evidence_type: IMP
  original_reference_id: PMID:18231602
  review:
    summary: Beta-catenin governs lung branching and cell-fate programs through Wnt transcription; a respiratory organ-development outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven lung development
    supported_by:
    - reference_id: PMID:18231602
      supporting_text: Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
- term:
    id: GO:0030539
    label: male genitalia development
  evidence_type: IMP
  original_reference_id: PMID:19282366
  review:
    summary: Beta-catenin drives male external genital outgrowth/patterning via Wnt transcription; a urogenital developmental outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven male genitalia development
    supported_by:
    - reference_id: PMID:19282366
      supporting_text: Genetic interactions of the androgen and Wnt/beta-catenin pathways for the masculinization of external genitalia.
- term:
    id: GO:0030856
    label: regulation of epithelial cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:12813461
  review:
    summary: Generic epithelial-differentiation regulation reflects beta-catenin's Wnt control of epithelial fate; a downstream umbrella process.
    action: KEEP_AS_NON_CORE
    reason: Epithelial fate regulation downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:12813461
      supporting_text: Activation of beta-catenin in prostate epithelium induces hyperplasias and squamous transdifferentiation.
- term:
    id: GO:0030858
    label: positive regulation of epithelial cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:16040629
  review:
    summary: Beta-catenin promotes epithelial differentiation in several tissues via Wnt-target transcription; a downstream lineage phenotype.
    action: KEEP_AS_NON_CORE
    reason: Epithelial differentiation downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:16040629
      supporting_text: Beta-catenin regulates differentiation of respiratory epithelial cells in vivo.
- term:
    id: GO:0030900
    label: forebrain development
  evidence_type: IMP
  original_reference_id: PMID:15708565
  review:
    summary: Beta-catenin patterns forebrain via Wnt/TCF neural transcription and progenitor control; a CNS developmental outcome, not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven forebrain development
    supported_by:
    - reference_id: PMID:15708565
      supporting_text: Effects of canonical Wnt signaling on dorso-ventral specification of the mouse telencephalon.
- term:
    id: GO:0031016
    label: pancreas development
  evidence_type: IMP
  original_reference_id: PMID:16192304
  review:
    summary: Beta-catenin Wnt signaling is required for pancreatic growth and acinar development; a downstream organ-development phenotype.
    action: KEEP_AS_NON_CORE
    reason: Pancreas development downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:16192304
      supporting_text: Beta-catenin is essential for pancreatic acinar but not islet development.
- term:
    id: GO:0031069
    label: hair follicle morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:11371349
  review:
    summary: Beta-catenin is essential for hair-follicle morphogenesis through epidermal Wnt/TCF transcription; an ectodermal appendage outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven hair follicle morphogenesis
    supported_by:
    - reference_id: PMID:11371349
      supporting_text: beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin.
- term:
    id: GO:0031069
    label: hair follicle morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:24309208
  review:
    summary: Beta-catenin is essential for hair-follicle morphogenesis through epidermal Wnt/TCF transcription; an ectodermal appendage outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven hair follicle morphogenesis
    supported_by:
    - reference_id: PMID:24309208
      supporting_text: Wnt/Ξ²-catenin signaling in dermal condensates is required for hair follicle formation.
- term:
    id: GO:0031641
    label: regulation of myelination
  evidence_type: IMP
  original_reference_id: PMID:19515974
  review:
    summary: Beta-catenin modulates myelination via Wnt-dependent control of oligodendrocyte maturation; a downstream glial/CNS phenotype.
    action: KEEP_AS_NON_CORE
    reason: Myelination control downstream of Wnt oligodendrocyte transcription.
    supported_by:
    - reference_id: PMID:19515974
      supporting_text: Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS.
- term:
    id: GO:0032331
    label: negative regulation of chondrocyte differentiation
  evidence_type: IGI
  original_reference_id: PMID:16818445
  review:
    summary: Beta-catenin Wnt signaling biases skeletal progenitors away from chondrogenesis toward osteogenesis; a genetic-interaction downstream skeletal phenotype.
    action: KEEP_AS_NON_CORE
    reason: Chondrocyte suppression downstream of Wnt fate-switch transcription.
    supported_by:
    - reference_id: PMID:16818445
      supporting_text: Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis.
- term:
    id: GO:0033077
    label: T cell differentiation in thymus
  evidence_type: IMP
  original_reference_id: PMID:16025118
  review:
    summary: Thymic T-cell differentiation requires Wnt/beta-catenin transcriptional signaling; a tissue-specific lymphoid maturation phenotype downstream of TCF co-activation.
    action: KEEP_AS_NON_CORE
    reason: tissue-specific downstream Wnt output in thymus
    supported_by:
    - reference_id: PMID:16025118
      supporting_text: Loss of adenomatous polyposis coli gene function disrupts thymic development.
- term:
    id: GO:0034332
    label: adherens junction organization
  evidence_type: IMP
  original_reference_id: PMID:19129494
  review:
    summary: Beta-catenin organizes adherens junctions through the cadherin-catenin complex; loss perturbs junction integrity.
    action: ACCEPT
    reason: Core adhesion process; IMP-supported.
    supported_by:
    - reference_id: PMID:19129494
      supporting_text: Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis.
- term:
    id: GO:0035050
    label: embryonic heart tube development
  evidence_type: IMP
  original_reference_id: PMID:18231602
  review:
    summary: Beta-catenin contributes to heart-tube formation via Wnt-driven cardiac progenitor programs; a cardiac developmental outcome, not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven heart tube development
    supported_by:
    - reference_id: PMID:18231602
      supporting_text: Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
- term:
    id: GO:0035112
    label: genitalia morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:18635608
  review:
    summary: Beta-catenin shapes external genitalia via Wnt-driven outgrowth and patterning; a urogenital morphogenetic outcome downstream of transcription.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven genital morphogenesis
    supported_by:
    - reference_id: PMID:18635608
      supporting_text: Tissue-specific requirements of beta-catenin in external genitalia development.
- term:
    id: GO:0035115
    label: embryonic forelimb morphogenesis
  evidence_type: IDA
  original_reference_id: PMID:15371327
  review:
    summary: Beta-catenin drives forelimb outgrowth/patterning through Wnt-driven AER maintenance (IDA); a limb developmental outcome downstream of its signaling role.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven forelimb morphogenesis
    supported_by:
    - reference_id: PMID:15371327
      supporting_text: Wnt/beta-catenin signaling is sufficient and necessary for synovial joint formation.
- term:
    id: GO:0035116
    label: embryonic hindlimb morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:12923052
  review:
    summary: Beta-catenin drives hindlimb outgrowth/patterning via Wnt signaling in limb mesenchyme/AER; a limb morphogenetic outcome downstream of transcription.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven hindlimb morphogenesis
    supported_by:
    - reference_id: PMID:12923052
      supporting_text: Genetic interaction between Wnt/beta-catenin and BMP receptor signaling during formation of the AER and the dorsal-ventral axis in the limb.
- term:
    id: GO:0035116
    label: embryonic hindlimb morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:18231602
  review:
    summary: Beta-catenin drives hindlimb outgrowth/patterning via Wnt signaling in limb mesenchyme/AER; a limb morphogenetic outcome downstream of transcription.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven hindlimb morphogenesis
    supported_by:
    - reference_id: PMID:18231602
      supporting_text: Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
- term:
    id: GO:0042127
    label: regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:12235125
  review:
    summary: Generic proliferation regulation reflects beta-catenin's Wnt mitogenic transcriptional program; downstream and non-specific.
    action: KEEP_AS_NON_CORE
    reason: Umbrella proliferation regulation downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:12235125
      supporting_text: Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor.
- term:
    id: GO:0042127
    label: regulation of cell population proliferation
  evidence_type: IMP
  original_reference_id: PMID:17055474
  review:
    summary: Generic proliferation regulation reflects beta-catenin's Wnt mitogenic transcriptional program; downstream and non-specific.
    action: KEEP_AS_NON_CORE
    reason: Umbrella proliferation regulation downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:17055474
      supporting_text: The stabilization of beta-catenin leads to impaired primordial germ cell development via aberrant cell cycle progression.
- term:
    id: GO:0042127
    label: regulation of cell population proliferation
  evidence_type: IMP
  original_reference_id: PMID:18635608
  review:
    summary: Generic proliferation regulation reflects beta-catenin's Wnt mitogenic transcriptional program; downstream and non-specific.
    action: KEEP_AS_NON_CORE
    reason: Umbrella proliferation regulation downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:18635608
      supporting_text: Tissue-specific requirements of beta-catenin in external genitalia development.
- term:
    id: GO:0042129
    label: regulation of T cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:14608382
  review:
    summary: Beta-catenin Wnt signaling modulates T-cell expansion during lymphopoiesis; a downstream immune-development phenotype.
    action: KEEP_AS_NON_CORE
    reason: T-cell proliferation control downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:14608382
      supporting_text: Deletion of beta-catenin impairs T cell development.
- term:
    id: GO:0042475
    label: odontogenesis of dentin-containing tooth
  evidence_type: IMP
  original_reference_id: PMID:15866165
  review:
    summary: Beta-catenin Wnt signaling is essential for tooth morphogenesis and dentinogenesis; a downstream organ-development phenotype.
    action: KEEP_AS_NON_CORE
    reason: Tooth development downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:15866165
      supporting_text: Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
- term:
    id: GO:0042733
    label: embryonic digit morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:12923052
  review:
    summary: Beta-catenin shapes digit formation in the limb through Wnt-driven AER and mesenchymal programs; a limb morphogenetic outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven digit morphogenesis
    supported_by:
    - reference_id: PMID:12923052
      supporting_text: Genetic interaction between Wnt/beta-catenin and BMP receptor signaling during formation of the AER and the dorsal-ventral axis in the limb.
- term:
    id: GO:0042733
    label: embryonic digit morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:20043884
  review:
    summary: Beta-catenin shapes digit formation in the limb through Wnt-driven AER and mesenchymal programs; a limb morphogenetic outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven digit morphogenesis
    supported_by:
    - reference_id: PMID:20043884
      supporting_text: Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling within the Apical Ectodermal Ridge (AER) regulates interdigit formation.
- term:
    id: GO:0042733
    label: embryonic digit morphogenesis
  evidence_type: IGI
  original_reference_id: PMID:20043884
  review:
    summary: Beta-catenin shapes digit formation in the limb through Wnt-driven AER and mesenchymal programs; a limb morphogenetic outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven digit morphogenesis
    supported_by:
    - reference_id: PMID:20043884
      supporting_text: Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling within the Apical Ectodermal Ridge (AER) regulates interdigit formation.
- term:
    id: GO:0042981
    label: regulation of apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:20043884
  review:
    summary: Generic apoptosis regulation reflects beta-catenin's transcriptional control of survival/death genes; a downstream, non-specific regulatory role.
    action: KEEP_AS_NON_CORE
    reason: Umbrella survival/death regulation downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:20043884
      supporting_text: Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling within the Apical Ectodermal Ridge (AER) regulates interdigit formation.
- term:
    id: GO:0043410
    label: positive regulation of MAPK cascade
  evidence_type: IGI
  original_reference_id: PMID:16478791
  review:
    summary: IGI-supported genetic interaction with MAPK signaling; a crosstalk effect rather than beta-catenin's core Wnt/transcription function.
    action: KEEP_AS_NON_CORE
    reason: Crosstalk regulatory effect; non-core (experimental IGI, not removed).
    supported_by:
    - reference_id: PMID:16478791
      supporting_text: APC inhibits ERK pathway activation and cellular proliferation induced by RAS.
- term:
    id: GO:0043524
    label: negative regulation of neuron apoptotic process
  evidence_type: IGI
  original_reference_id: PMID:22956852
  review:
    summary: Beta-catenin protects neurons from apoptosis in genetic-interaction assays, consistent with Wnt-driven survival transcription; a neuron-specific downstream phenotype.
    action: KEEP_AS_NON_CORE
    reason: Neuronal survival downstream of Wnt/beta-catenin transcriptional targets.
    supported_by:
    - reference_id: PMID:22956852
      supporting_text: Integration of Ξ²-catenin, sirtuin, and FOXO signaling protects from mutant huntingtin toxicity.
- term:
    id: GO:0043588
    label: skin development
  evidence_type: IMP
  original_reference_id: PMID:19718027
  review:
    summary: Beta-catenin Wnt signaling governs epidermal/appendage development; a downstream organ-system phenotype combining adhesion and transcription roles.
    action: KEEP_AS_NON_CORE
    reason: Skin development downstream of Wnt transcription and adhesion.
    supported_by:
    - reference_id: PMID:19718027
      supporting_text: Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia.
- term:
    id: GO:0045453
    label: bone resorption
  evidence_type: IMP
  original_reference_id: PMID:15866165
  review:
    summary: Beta-catenin shifts osteoblast/osteoclast balance (e.g. OPG induction) via Wnt/TCF transcription, regulating resorption; a skeletal-remodeling outcome, not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream of Wnt-driven osteo-transcriptional balance
    supported_by:
    - reference_id: PMID:15866165
      supporting_text: Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
- term:
    id: GO:0045453
    label: bone resorption
  evidence_type: IGI
  original_reference_id: PMID:15866165
  review:
    summary: Beta-catenin shifts osteoblast/osteoclast balance (e.g. OPG induction) via Wnt/TCF transcription, regulating resorption; a skeletal-remodeling outcome, not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream of Wnt-driven osteo-transcriptional balance
    supported_by:
    - reference_id: PMID:15866165
      supporting_text: Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
- term:
    id: GO:0045595
    label: regulation of cell differentiation
  evidence_type: IDA
  original_reference_id: PMID:12717450
  review:
    summary: IDA-level generic differentiation regulation summarizes beta-catenin's transcriptional control of many fate decisions; a downstream umbrella process.
    action: KEEP_AS_NON_CORE
    reason: Broad differentiation control downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:12717450
      supporting_text: A role for Wnt signalling in self-renewal of haematopoietic stem cells.
- term:
    id: GO:0045596
    label: negative regulation of cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:15866163
  review:
    summary: Beta-catenin can hold progenitors undifferentiated via Wnt-target transcription (stemness genes); a broad downstream differentiation-blocking phenotype.
    action: KEEP_AS_NON_CORE
    reason: Differentiation suppression downstream of Wnt stemness-gene transcription.
    supported_by:
    - reference_id: PMID:15866163
      supporting_text: Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
- term:
    id: GO:0045596
    label: negative regulation of cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:16102745
  review:
    summary: Beta-catenin can hold progenitors undifferentiated via Wnt-target transcription (stemness genes); a broad downstream differentiation-blocking phenotype.
    action: KEEP_AS_NON_CORE
    reason: Differentiation suppression downstream of Wnt stemness-gene transcription.
    supported_by:
    - reference_id: PMID:16102745
      supporting_text: 'The duality of beta-catenin function: a requirement in lens morphogenesis and signaling suppression of lens fate in periocular ectoderm.'
- term:
    id: GO:0045603
    label: positive regulation of endothelial cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:18231602
  review:
    summary: Wnt/beta-catenin transcription supports endothelial cell fate during vascular development; the differentiation outcome is downstream.
    action: KEEP_AS_NON_CORE
    reason: Endothelial differentiation downstream of Wnt-target transcription.
    supported_by:
    - reference_id: PMID:18231602
      supporting_text: Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
- term:
    id: GO:0045667
    label: regulation of osteoblast differentiation
  evidence_type: IMP
  original_reference_id: PMID:15576404
  review:
    summary: Generic osteoblast-differentiation regulation summarizes beta-catenin's Wnt control of bone-forming cell fate; downstream and somewhat redundant.
    action: KEEP_AS_NON_CORE
    reason: Osteoblast fate regulation downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:15576404
      supporting_text: Sequential roles of Hedgehog and Wnt signaling in osteoblast development.
- term:
    id: GO:0045667
    label: regulation of osteoblast differentiation
  evidence_type: IMP
  original_reference_id: PMID:15802266
  review:
    summary: Generic osteoblast-differentiation regulation summarizes beta-catenin's Wnt control of bone-forming cell fate; downstream and somewhat redundant.
    action: KEEP_AS_NON_CORE
    reason: Osteoblast fate regulation downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:15802266
      supporting_text: Essential role of beta-catenin in postnatal bone acquisition.
- term:
    id: GO:0045669
    label: positive regulation of osteoblast differentiation
  evidence_type: IMP
  original_reference_id: PMID:15866163
  review:
    summary: Beta-catenin promotes osteoblast differentiation by activating osteogenic Wnt targets; a downstream, lineage-specific developmental role.
    action: KEEP_AS_NON_CORE
    reason: Pro-osteoblast effect downstream of Wnt osteogenic transcription.
    supported_by:
    - reference_id: PMID:15866163
      supporting_text: Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
- term:
    id: GO:0045670
    label: regulation of osteoclast differentiation
  evidence_type: IMP
  original_reference_id: PMID:15802266
  review:
    summary: Beta-catenin regulates osteoclastogenesis indirectly via osteoblast RANKL/OPG transcription; a downstream bone-remodeling control.
    action: KEEP_AS_NON_CORE
    reason: Osteoclast regulation downstream of Wnt-driven osteoblast signaling.
    supported_by:
    - reference_id: PMID:15802266
      supporting_text: Essential role of beta-catenin in postnatal bone acquisition.
- term:
    id: GO:0045671
    label: negative regulation of osteoclast differentiation
  evidence_type: IMP
  original_reference_id: PMID:15866165
  review:
    summary: Osteoblast-lineage beta-catenin Wnt signaling raises OPG to restrain osteoclastogenesis; a downstream bone-remodeling phenotype.
    action: KEEP_AS_NON_CORE
    reason: Osteoclast suppression downstream of Wnt-driven OPG transcription.
    supported_by:
    - reference_id: PMID:15866165
      supporting_text: Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
- term:
    id: GO:0045743
    label: positive regulation of fibroblast growth factor receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:18231602
  review:
    summary: Beta-catenin Wnt output can up-regulate FGF ligands/receptors, amplifying FGFR signaling; a downstream signaling-crosstalk phenotype.
    action: KEEP_AS_NON_CORE
    reason: FGFR pathway boost downstream of Wnt-target transcription.
    supported_by:
    - reference_id: PMID:18231602
      supporting_text: Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
- term:
    id: GO:0045743
    label: positive regulation of fibroblast growth factor receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:18533146
  review:
    summary: Beta-catenin Wnt output can up-regulate FGF ligands/receptors, amplifying FGFR signaling; a downstream signaling-crosstalk phenotype.
    action: KEEP_AS_NON_CORE
    reason: FGFR pathway boost downstream of Wnt-target transcription.
    supported_by:
    - reference_id: PMID:18533146
      supporting_text: An FGF-WNT gene regulatory network controls lung mesenchyme development.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:12551949
  review:
    summary: beta-catenin can repress specific targets (e.g. via SOX9/TCF competition or unliganded-TCF contexts), but its core, defining transcriptional role is positive coactivation of TCF/LEF targets.
    action: KEEP_AS_NON_CORE
    reason: Context-dependent repression; secondary to its activating role.
    supported_by:
    - reference_id: PMID:12551949
      supporting_text: Lymphoid enhancer factor-1 and beta-catenin inhibit Runx2-dependent transcriptional activation of the osteocalcin promoter.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IMP
  original_reference_id: PMID:15866163
  review:
    summary: beta-catenin can repress specific targets (e.g. via SOX9/TCF competition or unliganded-TCF contexts), but its core, defining transcriptional role is positive coactivation of TCF/LEF targets.
    action: KEEP_AS_NON_CORE
    reason: Context-dependent repression; secondary to its activating role.
    supported_by:
    - reference_id: PMID:15866163
      supporting_text: Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:10631168
  review:
    summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
    action: MODIFY
    reason: Generic parent; specialize to Pol II-specific positive regulation.
    proposed_replacement_terms: &id002
    - id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    supported_by:
    - reference_id: PMID:10631168
      supporting_text: Hippocampus development and generation of dentate gyrus granule cells is regulated by LEF1.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:12551949
  review:
    summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
    action: MODIFY
    reason: Generic parent; specialize to Pol II-specific positive regulation.
    proposed_replacement_terms: *id002
    supported_by:
    - reference_id: PMID:12551949
      supporting_text: Lymphoid enhancer factor-1 and beta-catenin inhibit Runx2-dependent transcriptional activation of the osteocalcin promoter.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IMP
  original_reference_id: PMID:15866163
  review:
    summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
    action: MODIFY
    reason: Generic parent; specialize to Pol II-specific positive regulation.
    proposed_replacement_terms: *id002
    supported_by:
    - reference_id: PMID:15866163
      supporting_text: Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:16936075
  review:
    summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
    action: MODIFY
    reason: Generic parent; specialize to Pol II-specific positive regulation.
    proposed_replacement_terms: *id002
    supported_by:
    - reference_id: PMID:16936075
      supporting_text: The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 expression during somitogenesis.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IMP
  original_reference_id: PMID:17767158
  review:
    summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
    action: MODIFY
    reason: Generic parent; specialize to Pol II-specific positive regulation.
    proposed_replacement_terms: *id002
    supported_by:
    - reference_id: PMID:17767158
      supporting_text: Modulation of morphogenesis by noncanonical Wnt signaling requires ATF/CREB family-mediated transcriptional activation of TGFbeta2.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:19056892
  review:
    summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
    action: MODIFY
    reason: Generic parent; specialize to Pol II-specific positive regulation.
    proposed_replacement_terms: *id002
    supported_by:
    - reference_id: PMID:19056892
      supporting_text: A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IMP
  original_reference_id: PMID:19690384
  review:
    summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
    action: MODIFY
    reason: Generic parent; specialize to Pol II-specific positive regulation.
    proposed_replacement_terms: *id002
    supported_by:
    - reference_id: PMID:19690384
      supporting_text: Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:15024079
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
    supported_by:
    - reference_id: PMID:15024079
      supporting_text: Brn-2 expression controls melanoma proliferation and is directly regulated by beta-catenin.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IGI
  original_reference_id: PMID:15729346
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
    supported_by:
    - reference_id: PMID:15729346
      supporting_text: Pax3 functions at a nodal point in melanocyte stem cell differentiation.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IGI
  original_reference_id: PMID:15778706
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
    supported_by:
    - reference_id: PMID:15778706
      supporting_text: Wnt signalling induces maturation of Paneth cells in intestinal crypts.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:15907834
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
    supported_by:
    - reference_id: PMID:15907834
      supporting_text: Wnt/beta-catenin signaling acts upstream of N-myc, BMP4, and FGF signaling to regulate proximal-distal patterning in the lung.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IGI
  original_reference_id: PMID:16678101
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
    supported_by:
    - reference_id: PMID:16678101
      supporting_text: Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:19620969
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
    supported_by:
    - reference_id: PMID:19620969
      supporting_text: A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:20159597
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
    supported_by:
    - reference_id: PMID:20159597
      supporting_text: Characterization and in vivo pharmacological rescue of a Wnt2-Gata6 pathway required for cardiac inflow tract development.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:20627076
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
    supported_by:
    - reference_id: PMID:20627076
      supporting_text: The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/Notch signaling.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:21750544
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
    supported_by:
    - reference_id: PMID:21750544
      supporting_text: The Wnt3a/Ξ²-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program.
- term:
    id: GO:0048469
    label: cell maturation
  evidence_type: IMP
  original_reference_id: PMID:15576404
  review:
    summary: Beta-catenin supports terminal cell maturation in several lineages through Wnt transcriptional output; a differentiation-completion outcome (IDA/IMP), not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream maturation of Wnt-target lineages
    supported_by:
    - reference_id: PMID:15576404
      supporting_text: Sequential roles of Hedgehog and Wnt signaling in osteoblast development.
- term:
    id: GO:0048469
    label: cell maturation
  evidence_type: IDA
  original_reference_id: PMID:17706960
  review:
    summary: Beta-catenin supports terminal cell maturation in several lineages through Wnt transcriptional output; a differentiation-completion outcome (IDA/IMP), not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream maturation of Wnt-target lineages
    supported_by:
    - reference_id: PMID:17706960
      supporting_text: Persistent expression of stabilized beta-catenin delays maturation of radial glial cells into intermediate progenitors.
- term:
    id: GO:0048489
    label: synaptic vesicle transport
  evidence_type: IMP
  original_reference_id: PMID:14622577
  review:
    summary: Beta-catenin's cadherin scaffolding influences synaptic vesicle localization/transport; a downstream adhesion-linked synaptic phenotype.
    action: KEEP_AS_NON_CORE
    reason: Vesicle transport downstream of cadherin-adhesion scaffolding role.
    supported_by:
    - reference_id: PMID:14622577
      supporting_text: Role of beta-catenin in synaptic vesicle localization and presynaptic assembly.
- term:
    id: GO:0048513
    label: animal organ development
  evidence_type: IMP
  original_reference_id: PMID:18635608
  review:
    summary: Generic organ-development umbrella that conveys nothing specific about beta-catenin; the many specific organ terms already capture its Wnt-driven roles.
    action: MARK_AS_OVER_ANNOTATED
    reason: vague high-level umbrella adds no specificity
    supported_by:
    - reference_id: PMID:18635608
      supporting_text: Tissue-specific requirements of beta-catenin in external genitalia development.
- term:
    id: GO:0048538
    label: thymus development
  evidence_type: IMP
  original_reference_id: PMID:16025118
  review:
    summary: Beta-catenin Wnt signaling supports thymic epithelial/lymphoid development; a downstream organ-development phenotype.
    action: KEEP_AS_NON_CORE
    reason: Thymus development downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:16025118
      supporting_text: Loss of adenomatous polyposis coli gene function disrupts thymic development.
- term:
    id: GO:0048599
    label: oocyte development
  evidence_type: IGI
  original_reference_id: PMID:20454446
  review:
    summary: Beta-catenin influences oogenesis in genetic-interaction assays, likely via Wnt-transcriptional control of follicular signaling; a downstream germ-cell phenotype.
    action: KEEP_AS_NON_CORE
    reason: Oocyte development downstream of Wnt transcription; non-core.
    supported_by:
    - reference_id: PMID:20454446
      supporting_text: WNT4/beta-catenin pathway maintains female germ cell survival by inhibiting activin betaB in the mouse fetal ovary.
- term:
    id: GO:0048617
    label: embryonic foregut morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:18692041
  review:
    summary: Beta-catenin patterns foregut endoderm via Wnt/TCF transcription enabling organ budding; a gut morphogenetic outcome, not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven foregut morphogenesis
    supported_by:
    - reference_id: PMID:18692041
      supporting_text: 'Bmp4 is required for tracheal formation: a novel mouse model for tracheal agenesis.'
- term:
    id: GO:0048715
    label: negative regulation of oligodendrocyte differentiation
  evidence_type: IMP
  original_reference_id: PMID:19503085
  review:
    summary: Wnt/beta-catenin inhibits oligodendrocyte maturation (e.g. via Id targets); a downstream glial-fate phenotype.
    action: KEEP_AS_NON_CORE
    reason: Oligodendrocyte block downstream of Wnt transcriptional targets.
    supported_by:
    - reference_id: PMID:19503085
      supporting_text: HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction.
- term:
    id: GO:0050808
    label: synapse organization
  evidence_type: IMP
  original_reference_id: PMID:14622577
  review:
    summary: Beta-catenin organizes synapses through cadherin adhesion, a neuron-specific developmental/structural role.
    action: KEEP_AS_NON_CORE
    reason: Neuronal process; IMP, non-core.
    supported_by:
    - reference_id: PMID:14622577
      supporting_text: Role of beta-catenin in synaptic vesicle localization and presynaptic assembly.
- term:
    id: GO:0051145
    label: smooth muscle cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:19690384
  review:
    summary: Beta-catenin contributes to smooth muscle fate specification via Wnt-driven transcription; the differentiation outcome is downstream of that program.
    action: KEEP_AS_NON_CORE
    reason: Smooth-muscle fate is downstream transcriptional output, not core MF.
    supported_by:
    - reference_id: PMID:19690384
      supporting_text: Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.
- term:
    id: GO:0060066
    label: oviduct development
  evidence_type: IMP
  original_reference_id: PMID:17532316
  review:
    summary: Beta-catenin Wnt signaling patterns Mullerian-duct-derived oviduct; a downstream reproductive-organ development phenotype.
    action: KEEP_AS_NON_CORE
    reason: Oviduct development downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:17532316
      supporting_text: Essential roles of mesenchyme-derived beta-catenin in mouse MΓΌllerian duct morphogenesis.
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:12235125
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:12235125
      supporting_text: Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:12464179
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:12464179
      supporting_text: Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:12717450
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:12717450
      supporting_text: A role for Wnt signalling in self-renewal of haematopoietic stem cells.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:15781477
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:15781477
      supporting_text: Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:16678101
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:16678101
      supporting_text: Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:16818445
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:16818445
      supporting_text: Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:19060336
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:19060336
      supporting_text: A Wnt7b-dependent pathway regulates the orientation of epithelial cell division and establishes the cortico-medullary axis of the mammalian kidney.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:19619491
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:19619491
      supporting_text: Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:19686689
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:19686689
      supporting_text: Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:19690384
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:19690384
      supporting_text: Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:20454446
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:20454446
      supporting_text: WNT4/beta-catenin pathway maintains female germ cell survival by inhibiting activin betaB in the mouse fetal ovary.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:31222549
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:31222549
      supporting_text: The Shisa3 knockout mouse exhibits normal bone phenotype.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0060173
    label: limb development
  evidence_type: IMP
  original_reference_id: PMID:12569130
  review:
    summary: Beta-catenin is required for limb-bud outgrowth via Wnt-driven AER maintenance; a limb organ-development outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven limb development
    supported_by:
    - reference_id: PMID:12569130
      supporting_text: Ectodermal Wnt3/beta-catenin signaling is required for the establishment and maintenance of the apical ectodermal ridge.
- term:
    id: GO:0060439
    label: trachea morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:18231602
  review:
    summary: Beta-catenin shapes tracheal morphology during foregut development via Wnt targets; a downstream organ-morphogenesis phenotype.
    action: KEEP_AS_NON_CORE
    reason: Trachea morphogenesis downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:18231602
      supporting_text: Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
- term:
    id: GO:0060439
    label: trachea morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:18692041
  review:
    summary: Beta-catenin shapes tracheal morphology during foregut development via Wnt targets; a downstream organ-morphogenesis phenotype.
    action: KEEP_AS_NON_CORE
    reason: Trachea morphogenesis downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:18692041
      supporting_text: 'Bmp4 is required for tracheal formation: a novel mouse model for tracheal agenesis.'
- term:
    id: GO:0060440
    label: trachea formation
  evidence_type: IMP
  original_reference_id: PMID:19805295
  review:
    summary: Beta-catenin Wnt signaling is required for tracheal tube formation; a downstream respiratory-organ morphogenesis phenotype.
    action: KEEP_AS_NON_CORE
    reason: Trachea formation downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:19805295
      supporting_text: beta-Catenin promotes respiratory progenitor identity in mouse foregut.
- term:
    id: GO:0060441
    label: epithelial tube branching involved in lung morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:18231602
  review:
    summary: Beta-catenin drives lung airway branching through Wnt-driven epithelial-mesenchymal programs; a pulmonary morphogenetic outcome, not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven lung branching
    supported_by:
    - reference_id: PMID:18231602
      supporting_text: Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
- term:
    id: GO:0060479
    label: lung cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:19805295
  review:
    summary: Beta-catenin drives pulmonary cell-type differentiation via Wnt/TCF transcription; a lung cell-fate outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven lung cell differentiation
    supported_by:
    - reference_id: PMID:19805295
      supporting_text: beta-Catenin promotes respiratory progenitor identity in mouse foregut.
- term:
    id: GO:0060484
    label: lung-associated mesenchyme development
  evidence_type: IMP
  original_reference_id: PMID:18533146
  review:
    summary: Beta-catenin supports pulmonary mesenchyme development via Wnt-driven transcription enabling epithelial-mesenchymal crosstalk; a tissue developmental outcome.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven lung mesenchyme development
    supported_by:
    - reference_id: PMID:18533146
      supporting_text: An FGF-WNT gene regulatory network controls lung mesenchyme development.
- term:
    id: GO:0060492
    label: lung induction
  evidence_type: IMP
  original_reference_id: PMID:19686689
  review:
    summary: Beta-catenin participates in initial lung specification from foregut endoderm via Wnt transcription; an early organ-induction outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven lung induction
    supported_by:
    - reference_id: PMID:19686689
      supporting_text: Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut.
- term:
    id: GO:0060492
    label: lung induction
  evidence_type: IMP
  original_reference_id: PMID:19805295
  review:
    summary: Beta-catenin participates in initial lung specification from foregut endoderm via Wnt transcription; an early organ-induction outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven lung induction
    supported_by:
    - reference_id: PMID:19805295
      supporting_text: beta-Catenin promotes respiratory progenitor identity in mouse foregut.
- term:
    id: GO:0060742
    label: epithelial cell differentiation involved in prostate gland development
  evidence_type: IMP
  original_reference_id: PMID:12813461
  review:
    summary: Beta-catenin drives prostate epithelial differentiation via Wnt/TCF transcription; a tissue-specific cell-fate outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven prostate epithelial fate
    supported_by:
    - reference_id: PMID:12813461
      supporting_text: Activation of beta-catenin in prostate epithelium induces hyperplasias and squamous transdifferentiation.
- term:
    id: GO:0060769
    label: positive regulation of epithelial cell proliferation involved in prostate gland development
  evidence_type: IMP
  original_reference_id: PMID:12813461
  review:
    summary: Beta-catenin Wnt signaling drives prostate epithelial proliferation during gland development; a downstream organ-specific phenotype.
    action: KEEP_AS_NON_CORE
    reason: Prostate epithelial proliferation downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:12813461
      supporting_text: Activation of beta-catenin in prostate epithelium induces hyperplasias and squamous transdifferentiation.
- term:
    id: GO:0060789
    label: hair follicle placode formation
  evidence_type: IMP
  original_reference_id: PMID:11371349
  review:
    summary: Beta-catenin initiates hair placodes via Wnt/TCF transcription in epidermis (IGI/IMP); an early skin-appendage outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven hair placode initiation
    supported_by:
    - reference_id: PMID:11371349
      supporting_text: beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin.
- term:
    id: GO:0060789
    label: hair follicle placode formation
  evidence_type: IGI
  original_reference_id: PMID:19619491
  review:
    summary: Beta-catenin initiates hair placodes via Wnt/TCF transcription in epidermis (IGI/IMP); an early skin-appendage outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven hair placode initiation
    supported_by:
    - reference_id: PMID:19619491
      supporting_text: Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
- term:
    id: GO:0060916
    label: mesenchymal cell proliferation involved in lung development
  evidence_type: IMP
  original_reference_id: PMID:17128274
  review:
    summary: Beta-catenin sustains lung mesenchyme proliferation via Wnt transcription supporting branching; a tissue-specific growth outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven lung mesenchymal proliferation
    supported_by:
    - reference_id: PMID:17128274
      supporting_text: Wnt-beta-catenin signaling initiates taste papilla development.
- term:
    id: GO:0060916
    label: mesenchymal cell proliferation involved in lung development
  evidence_type: IMP
  original_reference_id: PMID:18231602
  review:
    summary: Beta-catenin sustains lung mesenchyme proliferation via Wnt transcription supporting branching; a tissue-specific growth outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven lung mesenchymal proliferation
    supported_by:
    - reference_id: PMID:18231602
      supporting_text: Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
- term:
    id: GO:0061047
    label: positive regulation of branching involved in lung morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:18533146
  review:
    summary: Beta-catenin Wnt signaling promotes airway branching during lung morphogenesis; a downstream organ-morphogenesis phenotype.
    action: KEEP_AS_NON_CORE
    reason: Lung branching downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:18533146
      supporting_text: An FGF-WNT gene regulatory network controls lung mesenchyme development.
- term:
    id: GO:0061198
    label: fungiform papilla formation
  evidence_type: IMP
  original_reference_id: PMID:17128274
  review:
    summary: Beta-catenin drives fungiform (taste) papilla formation through Wnt-driven placode programs; an ectodermal appendage outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven papilla placode formation
    supported_by:
    - reference_id: PMID:17128274
      supporting_text: Wnt-beta-catenin signaling initiates taste papilla development.
- term:
    id: GO:0072033
    label: renal vesicle formation
  evidence_type: IMP
  original_reference_id: PMID:17537789
  review:
    summary: Wnt/beta-catenin induces renal vesicles from cap mesenchyme, the first epithelial nephron unit; a downstream renal morphogenesis step.
    action: KEEP_AS_NON_CORE
    reason: Renal vesicle induction downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:17537789
      supporting_text: Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development.
- term:
    id: GO:0072053
    label: renal inner medulla development
  evidence_type: IMP
  original_reference_id: PMID:19060336
  review:
    summary: Beta-catenin Wnt signaling contributes to inner medullary patterning during kidney development; a downstream regional renal phenotype.
    action: KEEP_AS_NON_CORE
    reason: Inner-medulla development downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:19060336
      supporting_text: A Wnt7b-dependent pathway regulates the orientation of epithelial cell division and establishes the cortico-medullary axis of the mammalian kidney.
- term:
    id: GO:0072054
    label: renal outer medulla development
  evidence_type: IMP
  original_reference_id: PMID:19060336
  review:
    summary: Beta-catenin Wnt signaling shapes outer medullary kidney architecture; a downstream regional renal-development phenotype.
    action: KEEP_AS_NON_CORE
    reason: Outer-medulla development downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:19060336
      supporting_text: A Wnt7b-dependent pathway regulates the orientation of epithelial cell division and establishes the cortico-medullary axis of the mammalian kidney.
- term:
    id: GO:0072079
    label: nephron tubule formation
  evidence_type: IMP
  original_reference_id: PMID:17537789
  review:
    summary: Beta-catenin Wnt signaling drives mesenchyme-to-nephron-tubule conversion; a downstream renal morphogenesis phenotype.
    action: KEEP_AS_NON_CORE
    reason: Nephron tubule formation downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:17537789
      supporting_text: Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development.
- term:
    id: GO:0098609
    label: cell-cell adhesion
  evidence_type: IMP
  original_reference_id: PMID:16102745
  review:
    summary: Beta-catenin is essential for cadherin-based cell-cell adhesion, anchoring the adhesion complex to the cytoskeleton.
    action: ACCEPT
    reason: Core adhesion process; IBA/IMP-supported.
    supported_by:
    - reference_id: PMID:16102745
      supporting_text: 'The duality of beta-catenin function: a requirement in lens morphogenesis and signaling suppression of lens fate in periocular ectoderm.'
- term:
    id: GO:2000017
    label: positive regulation of determination of dorsal identity
  evidence_type: IDA
  original_reference_id: PMID:18316368
  review:
    summary: Nuclear beta-catenin specifies dorsal/organizer identity in early embryos via Wnt-target transcription; an IDA axis-patterning phenotype downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: Dorsal-axis specification downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:18316368
      supporting_text: Protein encoded by the Axin(Fu) allele effectively down-regulates Wnt signaling but exerts a dominant negative effect on c-Jun N-terminal kinase signaling.
- term:
    id: GO:2001234
    label: negative regulation of apoptotic signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:15131783
  review:
    summary: Genetic evidence links beta-catenin to dampening apoptotic signaling, plausibly via Wnt survival-gene transcription; a downstream regulatory phenotype.
    action: KEEP_AS_NON_CORE
    reason: Downstream survival-signaling modulation via Wnt transcription.
    supported_by:
    - reference_id: PMID:15131783
      supporting_text: 'Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin.'
- term:
    id: GO:2001234
    label: negative regulation of apoptotic signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:20454446
  review:
    summary: Genetic evidence links beta-catenin to dampening apoptotic signaling, plausibly via Wnt survival-gene transcription; a downstream regulatory phenotype.
    action: KEEP_AS_NON_CORE
    reason: Downstream survival-signaling modulation via Wnt transcription.
    supported_by:
    - reference_id: PMID:20454446
      supporting_text: WNT4/beta-catenin pathway maintains female germ cell survival by inhibiting activin betaB in the mouse fetal ovary.
- term:
    id: GO:2001234
    label: negative regulation of apoptotic signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:20454446
  review:
    summary: Genetic evidence links beta-catenin to dampening apoptotic signaling, plausibly via Wnt survival-gene transcription; a downstream regulatory phenotype.
    action: KEEP_AS_NON_CORE
    reason: Downstream survival-signaling modulation via Wnt transcription.
    supported_by:
    - reference_id: PMID:20454446
      supporting_text: WNT4/beta-catenin pathway maintains female germ cell survival by inhibiting activin betaB in the mouse fetal ovary.
- term:
    id: GO:0003676
    label: nucleic acid binding
  evidence_type: EXP
  original_reference_id: PMID:21075118
  review:
    summary: Beta-catenin does not bind DNA sequence-specifically; its genuine nucleic-acid-associated role is chromatin association within TCF/LEF complexes.
    action: MODIFY
    reason: Over-general/likely indirect; replace with chromatin binding which it genuinely does.
    proposed_replacement_terms:
    - id: GO:0003682
      label: chromatin binding
    supported_by:
    - reference_id: PMID:21075118
      supporting_text: Biochemical and structural characterization of Ξ²-catenin interactions with nonphosphorylated and CK2-phosphorylated Lef-1.
- term:
    id: GO:0001221
    label: transcription coregulator binding
  evidence_type: IPI
  original_reference_id: PMID:22723415
  review:
    summary: Binding to transcription coregulators broadens beta-catenin's coactivator interactions; specific TF/coactivator terms more directly capture the core Wnt role.
    action: KEEP_AS_NON_CORE
    reason: Generic-ish nuclear MF; IPI, supportive.
    supported_by:
    - reference_id: PMID:22723415
      supporting_text: Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
- term:
    id: GO:0098609
    label: cell-cell adhesion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Beta-catenin is essential for cadherin-based cell-cell adhesion, anchoring the adhesion complex to the cytoskeleton.
    action: ACCEPT
    reason: Core adhesion process; IBA/IMP-supported.
- term:
    id: GO:0045296
    label: cadherin binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
    action: ACCEPT
    reason: Core structural MF; crystallographically defined, IPI/IBA.
    supported_by:
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0016922
    label: nuclear receptor binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Beta-catenin coactivates several nuclear receptors (e.g. NR5A2, AR/ER), broadening its transcriptional crosstalk beyond the core TCF/LEF axis.
    action: KEEP_AS_NON_CORE
    reason: Crosstalk coactivation; non-core relative to TCF.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
- term:
    id: GO:0019903
    label: protein phosphatase binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Protein-phosphatase binding (e.g. PTPN6/PTPRJ) regulates tyrosine-phosphorylation of junctional beta-catenin, a regulatory interaction.
    action: KEEP_AS_NON_CORE
    reason: Regulatory partner; IBA/IPI, non-core.
- term:
    id: GO:0045294
    label: alpha-catenin binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Beta-catenin binds alpha-catenin via its N-terminal region, the key linkage coupling the cadherin-catenin complex to the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural MF; crystallographically defined, IPI/IDA.
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0016342
    label: catenin complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Beta-catenin is a defining member of the catenin (cadherin-catenin) complex linking cadherins to alpha-catenin/actin.
    action: ACCEPT
    reason: Core complex; broadly supported (IBA/IDA/IMP/ISS).
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.'
    action: ACCEPT
    reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
    supported_by:
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0000922
    label: spindle pole
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: A mitotic spindle-pole pool (via NEK2) reflects a centrosome-related moonlighting localization, distinct from core adhesion/Wnt roles.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization; IEA, non-core.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Beta-catenin has a reported centrosomal pool acting in centrosome cohesion/separation, distinct from its core adhesion and Wnt roles.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization; IDA but non-core moonlighting.
- term:
    id: GO:0005856
    label: cytoskeleton
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Cytoskeleton localization reflects indirect cortical actin association via the cadherin-catenin complex; the specific junctional terms are more informative.
    action: KEEP_AS_NON_CORE
    reason: Over-general CC parent; electronic.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0007155
    label: cell adhesion
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Generic cell adhesion is subsumed by the more specific cadherin-mediated cell-cell adhesion terms that capture beta-catenin's actual mechanism.
    action: KEEP_AS_NON_CORE
    reason: Over-general parent; electronic; specific child preferred.
- term:
    id: GO:0007399
    label: nervous system development
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Pure-IEA, system-wide nervous-system development is too high-level to be informative; beta-catenin's specific CNS roles are captured by finer child terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Vague IEA umbrella adding nothing over specific neural terms; over-annotation.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
    action: KEEP_AS_NON_CORE
    reason: Over-general CC parent.
- term:
    id: GO:0016055
    label: Wnt signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: beta-catenin acts specifically in the CANONICAL (beta-catenin-dependent) Wnt branch, not the non-canonical branches. The generic parent should be specialized.
    action: MODIFY
    reason: IEA generic parent; specific canonical child available and well supported.
    proposed_replacement_terms:
    - id: GO:0060070
      label: canonical Wnt signaling pathway
- term:
    id: GO:0045202
    label: synapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Synaptic localization supports cadherin-based synaptic adhesion in neurons, a tissue-specific pool.
    action: KEEP_AS_NON_CORE
    reason: Synapse localization; IDA/IEA, non-core.
- term:
    id: GO:0045216
    label: cell-cell junction organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Beta-catenin contributes to organizing cell-cell junctions through assembly of the cadherin-catenin adhesion complex.
    action: ACCEPT
    reason: Core adhesion process; consistent with junction roles.
- term:
    id: GO:0045296
    label: cadherin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
    action: ACCEPT
    reason: Core structural MF; crystallographically defined, IPI/IBA.
    supported_by:
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0070161
    label: anchoring junction
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Beta-catenin localizes to anchoring junctions (adherens junctions), consistent with its cadherin-catenin structural role.
    action: ACCEPT
    reason: Core localization parent of adherens junction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10481074
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:10481074
      supporting_text: A GSK3-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed phosphorylation of axin and beta-catenin.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10873669
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:10873669
      supporting_text: Identification of a novel beta-catenin-interacting protein.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10882138
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:10882138
      supporting_text: Structure of the dimerization and beta-catenin-binding region of alpha-catenin.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11348595
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:11348595
      supporting_text: The structure of the beta-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by beta-catenin.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12408825
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:12408825
      supporting_text: ICAT inhibits beta-catenin binding to Tcf/Lef-family transcription factors and the general coactivator p300 using independent structural modules.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12421363
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:12421363
      supporting_text: Axin negatively affects tau phosphorylation by glycogen synthase kinase 3beta.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12874278
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:12874278
      supporting_text: The PDZ protein tax-interacting protein-1 inhibits beta-catenin transcriptional activity and growth of colorectal cancer cells.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14691142
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:14691142
      supporting_text: alpha3beta1 integrin-CD151, a component of the cadherin-catenin complex, regulates PTPmu expression and cell-cell adhesion.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15327768
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:15327768
      supporting_text: Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16293619
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:16293619
      supporting_text: 'Thermodynamics of beta-catenin-ligand interactions: the roles of the N- and C-terminal tails in modulating binding affinity.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16678101
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:16678101
      supporting_text: Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19107203
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:19107203
      supporting_text: Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20531388
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:20531388
      supporting_text: Mutant huntingtin-impaired degradation of beta-catenin causes neurotoxicity in Huntington's disease.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20837657
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:20837657
      supporting_text: Abelson family kinases regulate Frizzled planar cell polarity signaling via Dsh phosphorylation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21103407
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:21103407
      supporting_text: The leukemia-associated Mllt10/Af10-Dot1l are Tcf4/Ξ²-catenin coactivators essential for intestinal homeostasis.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21552260
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:21552260
      supporting_text: Nemo kinase phosphorylates Ξ²-catenin to promote ommatidial rotation and connects core PCP factors to E-cadherin-Ξ²-catenin.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21730140
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:21730140
      supporting_text: Ezrin-mediated apical integrity is required for intestinal homeostasis.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21751375
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:21751375
      supporting_text: Functional analysis of novel phosphorylation sites of CREB-binding protein using mass spectrometry and mammalian two-hybrid assays.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22723415
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:22723415
      supporting_text: Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23273993
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:23273993
      supporting_text: Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25873176
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:25873176
      supporting_text: TGIF governs a feed-forward network that empowers Wnt signaling to drive mammary tumorigenesis.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26893351
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:26893351
      supporting_text: The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9264463
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:9264463
      supporting_text: A specific domain in alpha-catenin mediates binding to beta-catenin or plakoglobin.
- term:
    id: GO:0000209
    label: protein polyubiquitination
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: beta-catenin is the polyubiquitinated SUBSTRATE (K48 chains via SCF-BTRC), not the ligase; this IEA/ISO term reflects its targeting for degradation and is non-core.
    action: KEEP_AS_NON_CORE
    reason: Substrate (not catalytic) involvement; electronic, kept as non-core.
- term:
    id: GO:0000791
    label: euchromatin
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: beta-catenin localizes with active TCF/LEF target loci in euchromatin, consistent with its coactivator role, but this CC term is contextual rather than a core function statement.
    action: KEEP_AS_NON_CORE
    reason: Localization term supporting, but not equal to, its coactivator function.
- term:
    id: GO:0001649
    label: osteoblast differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Wnt/beta-catenin is a master driver of osteoblast fate via Runx2/Osterix-linked targets; the differentiation outcome is downstream of that transcription.
    action: KEEP_AS_NON_CORE
    reason: Osteoblastogenesis downstream of Wnt/beta-catenin transcriptional program.
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.'
    action: ACCEPT
    reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
    supported_by:
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005102
    label: signaling receptor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Reported signaling-receptor binding is a generic descriptor of regulatory contacts and not a core, mechanistically defined function.
    action: KEEP_AS_NON_CORE
    reason: Semi-generic MF; electronic, peripheral.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
- term:
    id: GO:0005667
    label: transcription regulator complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin is a component of transcription regulator complexes (with TCF/LEF and coactivators) that drive Wnt target gene expression.
    action: ACCEPT
    reason: Core nuclear Wnt effector complex; IDA-supported.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin has a reported centrosomal pool acting in centrosome cohesion/separation, distinct from its core adhesion and Wnt roles.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization; IDA but non-core moonlighting.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin has a cytosolic pool subject to destruction-complex regulation and Wnt-dependent stabilization.
    action: ACCEPT
    reason: Genuine pool; IDA/TAS-supported.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
    action: ACCEPT
    reason: Core junctional localization; IDA.
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005929
    label: cilium
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin is reported at the cilium where Wnt/cytoskeletal regulation occurs; an electronically inferred location (IEA/ISO) secondary to junction and nuclear pools.
    action: KEEP_AS_NON_CORE
    reason: electronic secondary localization, non-core
- term:
    id: GO:0005938
    label: cell cortex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin associates with the actin-rich cell cortex via the cadherin-catenin complex at cell-cell contacts.
    action: ACCEPT
    reason: Genuine cortical pool at junctions.
- term:
    id: GO:0007155
    label: cell adhesion
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic cell adhesion is subsumed by the more specific cadherin-mediated cell-cell adhesion terms that capture beta-catenin's actual mechanism.
    action: KEEP_AS_NON_CORE
    reason: Over-general parent; electronic; specific child preferred.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin is a Wnt-pathway effector and adherens-junction protein, not a component of EGFR signaling; this electronically propagated (IEA/ISO) term is biologically misattributed.
    action: REMOVE
    reason: electronic; EGFR pathway not a beta-catenin role
- term:
    id: GO:0008285
    label: negative regulation of cell population proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Electronic/ortholog-inferred anti-proliferative effect in some lineages, downstream of context-specific Wnt transcriptional output.
    action: KEEP_AS_NON_CORE
    reason: Context anti-proliferation downstream of transcription; non-core (electronic).
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Generic negative-regulation-of-expression parent; beta-catenin's specific repressive effects act at the level of Pol II transcription of particular targets.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative broad parent; specific Pol II transcription terms preferred.
- term:
    id: GO:0010717
    label: regulation of epithelial to mesenchymal transition
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic EMT regulation reflects beta-catenin's dual junctional and Wnt-transcriptional control of epithelial plasticity; an electronic/ortholog-inferred downstream process.
    action: KEEP_AS_NON_CORE
    reason: Downstream EMT control via Wnt transcription and cadherin-adhesion balance; non-core.
- term:
    id: GO:0010718
    label: positive regulation of epithelial to mesenchymal transition
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Nuclear beta-catenin drives EMT transcriptional programs (Snail/Twist targets) while loss of its junctional pool also promotes EMT; the process is downstream of both core roles.
    action: KEEP_AS_NON_CORE
    reason: EMT is a transcriptional/adhesion downstream output, not beta-catenin's direct molecular function.
- term:
    id: GO:0010909
    label: positive regulation of heparan sulfate proteoglycan biosynthetic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Ortholog/electronic-inferred up-regulation of HSPG biosynthesis, plausibly via Wnt transcriptional targets; a downstream biosynthetic effect.
    action: KEEP_AS_NON_CORE
    reason: HSPG biosynthesis upregulation downstream of transcription; non-core (electronic).
- term:
    id: GO:0014010
    label: Schwann cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Beta-catenin supports Schwann cell proliferation via Wnt/TCF transcriptional output; a peripheral-glia proliferation outcome downstream of its signaling role, not a core molecular function.
    action: KEEP_AS_NON_CORE
    reason: ISO-supported downstream Wnt-driven glial proliferation phenotype
- term:
    id: GO:0014704
    label: intercalated disc
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Beta-catenin is a core structural component of the cardiac intercalated disc, anchoring N-cadherin to the actin cytoskeleton (IDA/ISO); a direct adhesion-structure localization.
    action: ACCEPT
    reason: direct structural localization at cardiac junction
- term:
    id: GO:0016020
    label: membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
    action: KEEP_AS_NON_CORE
    reason: Over-general CC parent.
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
    action: ACCEPT
    reason: Genuine junctional pool; IDA-supported.
- term:
    id: GO:0016324
    label: apical plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Apical plasma membrane pool is a context-specific epithelial localization; beta-catenin junctions are chiefly apicolateral/lateral.
    action: KEEP_AS_NON_CORE
    reason: Secondary membrane subdomain; electronic (ISO).
- term:
    id: GO:0016328
    label: lateral plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Beta-catenin concentrates at the lateral membrane of epithelia where cadherin-based cell-cell junctions assemble.
    action: ACCEPT
    reason: Genuine core junctional membrane pool; IDA.
- term:
    id: GO:0016328
    label: lateral plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin concentrates at the lateral membrane of epithelia where cadherin-based cell-cell junctions assemble.
    action: ACCEPT
    reason: Genuine core junctional membrane pool; IDA.
- term:
    id: GO:0016342
    label: catenin complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin is a defining member of the catenin (cadherin-catenin) complex linking cadherins to alpha-catenin/actin.
    action: ACCEPT
    reason: Core complex; broadly supported (IBA/IDA/IMP/ISS).
- term:
    id: GO:0016922
    label: nuclear receptor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin coactivates several nuclear receptors (e.g. NR5A2, AR/ER), broadening its transcriptional crosstalk beyond the core TCF/LEF axis.
    action: KEEP_AS_NON_CORE
    reason: Crosstalk coactivation; non-core relative to TCF.
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Bare 'enzyme binding' is uninformative; beta-catenin's relevant enzyme contacts (GSK3B, CK1, kinases) are captured by specific kinase/phosphatase terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
- term:
    id: GO:0019900
    label: kinase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic kinase binding reflects contacts with regulatory kinases (GSK3B, CK1, CDKs); informative specificity is in destruction-complex and PTM annotations.
    action: KEEP_AS_NON_CORE
    reason: Semi-generic MF; electronic, peripheral.
- term:
    id: GO:0019902
    label: phosphatase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Phosphatase binding (e.g. PTPRJ/PTPRU) regulates the phosphorylation state of junctional beta-catenin, a regulatory interaction.
    action: KEEP_AS_NON_CORE
    reason: Regulatory partner; electronic, non-core.
- term:
    id: GO:0030054
    label: cell junction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin is a core cell-junction protein, concentrated at cadherin-based cell-cell junctions.
    action: ACCEPT
    reason: Core localization (junction parent).
- term:
    id: GO:0030331
    label: nuclear estrogen receptor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Estrogen-receptor binding represents nuclear-receptor coactivator crosstalk, secondary to TCF/LEF-based Wnt transcription.
    action: KEEP_AS_NON_CORE
    reason: Crosstalk partner; electronic, non-core.
- term:
    id: GO:0030877
    label: beta-catenin destruction complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: In the absence of Wnt, beta-catenin is the substrate within the AXIN/APC/GSK3B/CK1 destruction complex that drives its phosphorylation and degradation.
    action: ACCEPT
    reason: Core Wnt regulation; defining complex membership (IDA/ISS).
- term:
    id: GO:0030997
    label: regulation of centriole-centriole cohesion
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin has a reported centrosomal moonlighting role in centriole cohesion; ortholog/electronic-inferred and distinct from its core adhesion/Wnt roles.
    action: KEEP_AS_NON_CORE
    reason: Centrosomal moonlighting role, electronic-inferred; non-core.
- term:
    id: GO:0031396
    label: regulation of protein ubiquitination
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Reflects beta-catenin being targeted for / influencing ubiquitination within the destruction complex; an IEA/ISO regulatory term peripheral to its effector function.
    action: KEEP_AS_NON_CORE
    reason: Indirect/substrate-side ubiquitination regulation; electronic, non-core.
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Binding E3 ligases (BTRC/SCF, SIAH1, UBR5) underlies beta-catenin's regulated turnover, a degradation-regulatory interaction.
    action: KEEP_AS_NON_CORE
    reason: Regulatory partner; ISO, non-core.
- term:
    id: GO:0031965
    label: nuclear membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: A nuclear-membrane pool may reflect nucleocytoplasmic shuttling, peripheral to the functional nuclear (chromatin/TCF) and junctional pools.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization; ISO.
- term:
    id: GO:0032355
    label: response to estradiol
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Ortholog/electronic-inferred responsiveness to estradiol, reflecting hormone crosstalk with Wnt/beta-catenin transcription in reproductive tissues; a downstream response.
    action: KEEP_AS_NON_CORE
    reason: Estradiol response downstream/crosstalk with Wnt transcription; non-core (electronic).
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Bare 'protein-containing complex' is uninformative; beta-catenin's specific complexes (catenin, TCF, destruction) are annotated separately.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic CC over-annotation.
- term:
    id: GO:0032993
    label: protein-DNA complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin is part of protein-DNA complexes only indirectly via TCF/LEF; the specific beta-catenin-TCF complex terms capture this better.
    action: KEEP_AS_NON_CORE
    reason: Indirect/over-general; electronic.
- term:
    id: GO:0033234
    label: negative regulation of protein sumoylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Ortholog/electronic-inferred negative effect on SUMOylation; an indirect downstream activity unrelated to beta-catenin's core adhesion/Wnt functions.
    action: KEEP_AS_NON_CORE
    reason: SUMOylation suppression, electronic-inferred and indirect; non-core.
- term:
    id: GO:0034097
    label: response to cytokine
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Sole ISO ortholog-transfer with no specific cytokine context; while crosstalk between beta-catenin and cytokine pathways exists, the bare term is too unspecific to confidently retain or refute.
    action: UNDECIDED
    reason: ISO-only, no specific evidence; mark UNDECIDED rather than REMOVE per electronic-evidence caution.
- term:
    id: GO:0034112
    label: positive regulation of homotypic cell-cell adhesion
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Promotion of homotypic adhesion follows from beta-catenin's cadherin role, but the directional regulatory term is electronic and secondary to the structural terms.
    action: KEEP_AS_NON_CORE
    reason: Regulatory process; IEA/ISO.
- term:
    id: GO:0034333
    label: adherens junction assembly
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: By linking cadherin to the catenin/actin machinery, beta-catenin is required for adherens junction assembly.
    action: ACCEPT
    reason: Core adhesion process; mechanistically central even if evidence is electronic/ISS.
- term:
    id: GO:0034394
    label: protein localization to cell surface
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin promotes surface delivery/retention of cadherin (e.g. via vinculin), a supporting trafficking role secondary to its structural function.
    action: KEEP_AS_NON_CORE
    reason: Peripheral process; electronic.
- term:
    id: GO:0035255
    label: ionotropic glutamate receptor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Reported binding to ionotropic glutamate receptors is a neuron-specific interaction tied to synaptic adhesion, not a core function.
    action: KEEP_AS_NON_CORE
    reason: Specific neuronal partner; ISO.
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin has been localized to the ciliary basal body, linking junction/centrosome pools; an electronically inferred location (IEA/ISO) peripheral to its core roles.
    action: KEEP_AS_NON_CORE
    reason: electronic minor localization, non-core
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: In some contexts beta-catenin promotes apoptosis; this electronic/ortholog-inferred bidirectional effect is a downstream consequence of context-specific transcription.
    action: KEEP_AS_NON_CORE
    reason: Context-dependent pro-apoptotic output downstream of transcription; non-core (electronic).
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin Wnt targets (e.g. survival genes) can suppress apoptosis; this electronic/ortholog-inferred pro-survival effect is downstream of transcription.
    action: KEEP_AS_NON_CORE
    reason: Anti-apoptotic effect downstream of Wnt-target gene expression; non-core (electronic).
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'Core to beta-catenin level control: phosphorylated beta-catenin is the SUBSTRATE ubiquitinated by SCF(BTRC) and degraded by the proteasome, the switch that gates Wnt signaling.'
    action: ACCEPT
    reason: Defining degradation process that regulates beta-catenin abundance.
    supported_by:
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research-falcon.md
      supporting_text: enabling recognition by **Ξ²-TrCP** (E3 ligase adaptor), ubiquitination, and proteasomal degradation
- term:
    id: GO:0043198
    label: dendritic shaft
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: The dendritic-shaft pool is a neuron-specific localization tied to synaptic adhesion, secondary to core junction/Wnt pools.
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific localization; ISO.
- term:
    id: GO:0043525
    label: positive regulation of neuron apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Ortholog-inferred pro-apoptotic effect on neurons in particular contexts, downstream of beta-catenin's transcriptional program.
    action: KEEP_AS_NON_CORE
    reason: Context-specific neuronal apoptosis downstream of Wnt transcription; non-core (electronic).
- term:
    id: GO:0043627
    label: response to estrogen
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: ISO ortholog-inferred estrogen responsiveness, consistent with estrogen-Wnt crosstalk in hormone-responsive tissues; a downstream response phenotype.
    action: KEEP_AS_NON_CORE
    reason: Estrogen response via hormone-Wnt crosstalk; non-core (electronic).
- term:
    id: GO:0044325
    label: transmembrane transporter binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Binding to transmembrane transporters/channels (e.g. TRPV4, SLC30A9) reflects context-specific interactions peripheral to core functions.
    action: KEEP_AS_NON_CORE
    reason: Specific peripheral partner class; electronic.
- term:
    id: GO:0044331
    label: cell-cell adhesion mediated by cadherin
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin mediates cadherin-dependent cell-cell adhesion, the precise process matching its molecular role.
    action: ACCEPT
    reason: Core, mechanistically specific adhesion term.
- term:
    id: GO:0044877
    label: protein-containing complex binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Generic 'complex binding' adds no functional specificity over the named complex-membership and partner-binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation; ISO.
- term:
    id: GO:0045294
    label: alpha-catenin binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Beta-catenin binds alpha-catenin via its N-terminal region, the key linkage coupling the cadherin-catenin complex to the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural MF; crystallographically defined, IPI/IDA.
- term:
    id: GO:0045294
    label: alpha-catenin binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin binds alpha-catenin via its N-terminal region, the key linkage coupling the cadherin-catenin complex to the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural MF; crystallographically defined, IPI/IDA.
- term:
    id: GO:0045296
    label: cadherin binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
    action: ACCEPT
    reason: Core structural MF; crystallographically defined, IPI/IBA.
    supported_by:
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0045296
    label: cadherin binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
    action: ACCEPT
    reason: Core structural MF; crystallographically defined, IPI/IBA.
    supported_by:
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: beta-catenin can repress specific targets (e.g. via SOX9/TCF competition or unliganded-TCF contexts), but its core, defining transcriptional role is positive coactivation of TCF/LEF targets.
    action: KEEP_AS_NON_CORE
    reason: Context-dependent repression; secondary to its activating role.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
    action: MODIFY
    reason: Generic parent; specialize to Pol II-specific positive regulation.
    proposed_replacement_terms: *id002
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
- term:
    id: GO:0046332
    label: SMAD binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: SMAD binding represents BMP/TGF-beta pathway crosstalk, secondary to beta-catenin's cadherin-adhesion and Wnt/TCF core functions.
    action: KEEP_AS_NON_CORE
    reason: Crosstalk; electronic (IEA/ISO) and not a core partner class.
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: A perinuclear cytoplasmic pool may reflect shuttling/staging intermediates, secondary to functional junctional and nuclear pools.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization; electronic.
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: A perinuclear cytoplasmic pool may reflect shuttling/staging intermediates, secondary to functional junctional and nuclear pools.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization; electronic.
- term:
    id: GO:0048660
    label: regulation of smooth muscle cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Modulation of vascular/visceral smooth muscle proliferation reflects Wnt/beta-catenin mitogenic target genes; ortholog/electronic-inferred downstream process.
    action: KEEP_AS_NON_CORE
    reason: Downstream proliferative control via Wnt transcriptional targets; non-core.
- term:
    id: GO:0050998
    label: nitric-oxide synthase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: eNOS-associated binding relates to S-nitrosylation-regulated junction disassembly in endothelium, a regulatory crosstalk interaction.
    action: KEEP_AS_NON_CORE
    reason: Specific partner; ISO, peripheral.
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0060231
    label: mesenchymal to epithelial transition
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin contributes to MET through cadherin-junction assembly and Wnt transcriptional balance; a cell-state transition (electronic) downstream of its dual role.
    action: KEEP_AS_NON_CORE
    reason: electronic; downstream of junction/Wnt MET role
- term:
    id: GO:0061154
    label: endothelial tube morphogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin supports endothelial tube formation via junctional integrity and Wnt transcription; a vascular morphogenetic outcome (electronic) downstream of its dual role.
    action: KEEP_AS_NON_CORE
    reason: electronic; downstream of junction/Wnt vascular roles
- term:
    id: GO:0061629
    label: RNA polymerase II-specific DNA-binding transcription factor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin directly binds Pol II-specific DNA-binding transcription factors (TCF/LEF) to drive Wnt-responsive transcription.
    action: ACCEPT
    reason: Core Wnt coactivation; IDA-supported specific TF binding.
- term:
    id: GO:0070097
    label: delta-catenin binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Binding to delta-catenin (CTNND2) occurs in neuronal contexts; p120/delta-catenin family members bind the cadherin juxtamembrane region, a secondary interaction for beta-catenin.
    action: KEEP_AS_NON_CORE
    reason: Specific partner binding; ISO and peripheral.
- term:
    id: GO:0070160
    label: tight junction
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Beta-catenin localizes to the tight-junction-associated region of the epithelial apical junctional complex via cadherin-catenin contacts.
    action: ACCEPT
    reason: Junctional localization within apical complex; retain (ISO).
- term:
    id: GO:0070369
    label: beta-catenin-TCF7L2 complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin forms the specific transcriptional complex with TCF7L2/TCF4 that activates Wnt target genes.
    action: ACCEPT
    reason: Core Wnt effector complex (specific TCF member).
- term:
    id: GO:0070411
    label: I-SMAD binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Inhibitory-SMAD binding reflects TGF-beta/BMP crosstalk rather than the canonical cadherin or Wnt/TCF functions of beta-catenin.
    action: KEEP_AS_NON_CORE
    reason: Crosstalk binding; electronic (IEA/ISO) and peripheral to core roles.
- term:
    id: GO:0070602
    label: regulation of centromeric sister chromatid cohesion
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: A reported beta-catenin role at centromeric cohesion is a moonlighting function separate from its Wnt/adhesion core; supported by IMP plus electronic inference.
    action: KEEP_AS_NON_CORE
    reason: Sister-chromatid cohesion moonlighting role; non-core to Wnt/adhesion.
- term:
    id: GO:0071260
    label: cellular response to mechanical stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Mechanical force at adherens junctions modulates beta-catenin release/signaling (mechanotransduction); a context response (ISO) downstream of its junctional role.
    action: KEEP_AS_NON_CORE
    reason: ISO mechanotransduction downstream of junction role
- term:
    id: GO:0071363
    label: cellular response to growth factor stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin participates in growth-factor-responsive transcription via Wnt crosstalk; a broad, electronically inferred response, kept as non-core given indirect linkage.
    action: KEEP_AS_NON_CORE
    reason: electronic/generic; indirect crosstalk, not core
- term:
    id: GO:0071681
    label: cellular response to indole-3-methanol
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: No credible biological basis for beta-catenin as a responder to indole-3-methanol; an electronically propagated (IEA/ISO/ISS) annotation with no support.
    action: REMOVE
    reason: electronic annotation biologically unsupported for this gene
- term:
    id: GO:0071944
    label: cell periphery
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin localizes to the cell periphery at adherens junctions linking cadherins to actin; a broad location term consistent with its structural role but less specific than the junction terms.
    action: KEEP_AS_NON_CORE
    reason: electronic broad location subsumed by adherens-junction terms
- term:
    id: GO:0072497
    label: mesenchymal stem cell differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin directs MSC lineage choice (osteo/chondro/adipo) via Wnt/TCF transcription; a stem-cell fate outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven MSC differentiation
- term:
    id: GO:0090279
    label: regulation of calcium ion import
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Ortholog/electronic-inferred influence on calcium import, distinct from beta-catenin's core Wnt/adhesion roles; a downstream/indirect effect.
    action: KEEP_AS_NON_CORE
    reason: Calcium-import regulation, electronic-inferred and indirect; non-core.
- term:
    id: GO:0098609
    label: cell-cell adhesion
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Beta-catenin is essential for cadherin-based cell-cell adhesion, anchoring the adhesion complex to the cytoskeleton.
    action: ACCEPT
    reason: Core adhesion process; IBA/IMP-supported.
- term:
    id: GO:0140297
    label: DNA-binding transcription factor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin binds TCF/LEF DNA-binding transcription factors to coactivate Wnt target genes; core to its nuclear Wnt-effector role.
    action: ACCEPT
    reason: 'Core Wnt: direct TCF/LEF coactivation (IPI); foundational MF for the transcriptional arm.'
- term:
    id: GO:1905555
    label: positive regulation of blood vessel branching
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin Wnt signaling promotes endothelial branching morphogenesis via target-gene expression; ortholog-inferred downstream vascular process.
    action: KEEP_AS_NON_CORE
    reason: Vessel branching is downstream of Wnt/beta-catenin endothelial transcription.
- term:
    id: GO:1990138
    label: neuron projection extension
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Ortholog/electronic-inferred role in axon/dendrite outgrowth, plausibly via cadherin-junction and Wnt-transcriptional inputs; a downstream neuronal phenotype.
    action: KEEP_AS_NON_CORE
    reason: Neurite extension downstream of adhesion/Wnt roles; non-core (electronic).
- term:
    id: GO:1990314
    label: cellular response to insulin-like growth factor stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Beta-catenin can be engaged in IGF-responsive transcriptional output via signaling crosstalk; an indirect response (ISO) kept as non-core, not a core IGF-pathway role.
    action: KEEP_AS_NON_CORE
    reason: ISO indirect IGF crosstalk, not core function
- term:
    id: GO:1990907
    label: beta-catenin-TCF complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: The nuclear beta-catenin-TCF complex is the central transcriptional effector unit of canonical Wnt signaling.
    action: ACCEPT
    reason: Core Wnt effector complex; IDA-supported.
- term:
    id: GO:2000008
    label: regulation of protein localization to cell surface
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Beta-catenin modulates cadherin surface levels, a regulatory trafficking role secondary to its structural junction function.
    action: KEEP_AS_NON_CORE
    reason: Peripheral regulatory process; electronic.
- term:
    id: GO:0000209
    label: protein polyubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: beta-catenin is the polyubiquitinated SUBSTRATE (K48 chains via SCF-BTRC), not the ligase; this IEA/ISO term reflects its targeting for degradation and is non-core.
    action: KEEP_AS_NON_CORE
    reason: Substrate (not catalytic) involvement; electronic, kept as non-core.
- term:
    id: GO:0000791
    label: euchromatin
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: beta-catenin localizes with active TCF/LEF target loci in euchromatin, consistent with its coactivator role, but this CC term is contextual rather than a core function statement.
    action: KEEP_AS_NON_CORE
    reason: Localization term supporting, but not equal to, its coactivator function.
- term:
    id: GO:0001649
    label: osteoblast differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Wnt/beta-catenin is a master driver of osteoblast fate via Runx2/Osterix-linked targets; the differentiation outcome is downstream of that transcription.
    action: KEEP_AS_NON_CORE
    reason: Osteoblastogenesis downstream of Wnt/beta-catenin transcriptional program.
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.'
    action: ACCEPT
    reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
    supported_by:
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005102
    label: signaling receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Reported signaling-receptor binding is a generic descriptor of regulatory contacts and not a core, mechanistically defined function.
    action: KEEP_AS_NON_CORE
    reason: Semi-generic MF; electronic, peripheral.
- term:
    id: GO:0005667
    label: transcription regulator complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin is a component of transcription regulator complexes (with TCF/LEF and coactivators) that drive Wnt target gene expression.
    action: ACCEPT
    reason: Core nuclear Wnt effector complex; IDA-supported.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin has a cytosolic pool subject to destruction-complex regulation and Wnt-dependent stabilization.
    action: ACCEPT
    reason: Genuine pool; IDA/TAS-supported.
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
    action: ACCEPT
    reason: Core junctional localization; IDA.
- term:
    id: GO:0005929
    label: cilium
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin is reported at the cilium where Wnt/cytoskeletal regulation occurs; an electronically inferred location (IEA/ISO) secondary to junction and nuclear pools.
    action: KEEP_AS_NON_CORE
    reason: electronic secondary localization, non-core
- term:
    id: GO:0005938
    label: cell cortex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin associates with the actin-rich cell cortex via the cadherin-catenin complex at cell-cell contacts.
    action: ACCEPT
    reason: Genuine cortical pool at junctions.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin is a Wnt-pathway effector and adherens-junction protein, not a component of EGFR signaling; this electronically propagated (IEA/ISO) term is biologically misattributed.
    action: REMOVE
    reason: electronic; EGFR pathway not a beta-catenin role
- term:
    id: GO:0008285
    label: negative regulation of cell population proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Electronic/ortholog-inferred anti-proliferative effect in some lineages, downstream of context-specific Wnt transcriptional output.
    action: KEEP_AS_NON_CORE
    reason: Context anti-proliferation downstream of transcription; non-core (electronic).
- term:
    id: GO:0009410
    label: response to xenobiotic stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: IEA-inferred xenobiotic responsiveness; an indirect downstream response not central to beta-catenin's adhesion or Wnt-transcriptional function.
    action: KEEP_AS_NON_CORE
    reason: Xenobiotic response, IEA-inferred and indirect; non-core.
    supported_by:
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research-falcon.md
      supporting_text: enabling recognition by **Ξ²-TrCP** (E3 ligase adaptor), ubiquitination, and proteasomal degradation
- term:
    id: GO:0010717
    label: regulation of epithelial to mesenchymal transition
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Generic EMT regulation reflects beta-catenin's dual junctional and Wnt-transcriptional control of epithelial plasticity; an electronic/ortholog-inferred downstream process.
    action: KEEP_AS_NON_CORE
    reason: Downstream EMT control via Wnt transcription and cadherin-adhesion balance; non-core.
- term:
    id: GO:0010718
    label: positive regulation of epithelial to mesenchymal transition
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Nuclear beta-catenin drives EMT transcriptional programs (Snail/Twist targets) while loss of its junctional pool also promotes EMT; the process is downstream of both core roles.
    action: KEEP_AS_NON_CORE
    reason: EMT is a transcriptional/adhesion downstream output, not beta-catenin's direct molecular function.
- term:
    id: GO:0010909
    label: positive regulation of heparan sulfate proteoglycan biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Ortholog/electronic-inferred up-regulation of HSPG biosynthesis, plausibly via Wnt transcriptional targets; a downstream biosynthetic effect.
    action: KEEP_AS_NON_CORE
    reason: HSPG biosynthesis upregulation downstream of transcription; non-core (electronic).
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
    action: ACCEPT
    reason: Genuine junctional pool; IDA-supported.
- term:
    id: GO:0016328
    label: lateral plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin concentrates at the lateral membrane of epithelia where cadherin-based cell-cell junctions assemble.
    action: ACCEPT
    reason: Genuine core junctional membrane pool; IDA.
- term:
    id: GO:0016342
    label: catenin complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin is a defining member of the catenin (cadherin-catenin) complex linking cadherins to alpha-catenin/actin.
    action: ACCEPT
    reason: Core complex; broadly supported (IBA/IDA/IMP/ISS).
- term:
    id: GO:0016922
    label: nuclear receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin coactivates several nuclear receptors (e.g. NR5A2, AR/ER), broadening its transcriptional crosstalk beyond the core TCF/LEF axis.
    action: KEEP_AS_NON_CORE
    reason: Crosstalk coactivation; non-core relative to TCF.
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Bare 'enzyme binding' is uninformative; beta-catenin's relevant enzyme contacts (GSK3B, CK1, kinases) are captured by specific kinase/phosphatase terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
- term:
    id: GO:0019900
    label: kinase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Generic kinase binding reflects contacts with regulatory kinases (GSK3B, CK1, CDKs); informative specificity is in destruction-complex and PTM annotations.
    action: KEEP_AS_NON_CORE
    reason: Semi-generic MF; electronic, peripheral.
- term:
    id: GO:0019902
    label: phosphatase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Phosphatase binding (e.g. PTPRJ/PTPRU) regulates the phosphorylation state of junctional beta-catenin, a regulatory interaction.
    action: KEEP_AS_NON_CORE
    reason: Regulatory partner; electronic, non-core.
- term:
    id: GO:0030054
    label: cell junction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin is a core cell-junction protein, concentrated at cadherin-based cell-cell junctions.
    action: ACCEPT
    reason: Core localization (junction parent).
- term:
    id: GO:0030331
    label: nuclear estrogen receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Estrogen-receptor binding represents nuclear-receptor coactivator crosstalk, secondary to TCF/LEF-based Wnt transcription.
    action: KEEP_AS_NON_CORE
    reason: Crosstalk partner; electronic, non-core.
- term:
    id: GO:0030877
    label: beta-catenin destruction complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: In the absence of Wnt, beta-catenin is the substrate within the AXIN/APC/GSK3B/CK1 destruction complex that drives its phosphorylation and degradation.
    action: ACCEPT
    reason: Core Wnt regulation; defining complex membership (IDA/ISS).
- term:
    id: GO:0030997
    label: regulation of centriole-centriole cohesion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin has a reported centrosomal moonlighting role in centriole cohesion; ortholog/electronic-inferred and distinct from its core adhesion/Wnt roles.
    action: KEEP_AS_NON_CORE
    reason: Centrosomal moonlighting role, electronic-inferred; non-core.
- term:
    id: GO:0031396
    label: regulation of protein ubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Reflects beta-catenin being targeted for / influencing ubiquitination within the destruction complex; an IEA/ISO regulatory term peripheral to its effector function.
    action: KEEP_AS_NON_CORE
    reason: Indirect/substrate-side ubiquitination regulation; electronic, non-core.
- term:
    id: GO:0032355
    label: response to estradiol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Ortholog/electronic-inferred responsiveness to estradiol, reflecting hormone crosstalk with Wnt/beta-catenin transcription in reproductive tissues; a downstream response.
    action: KEEP_AS_NON_CORE
    reason: Estradiol response downstream/crosstalk with Wnt transcription; non-core (electronic).
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Bare 'protein-containing complex' is uninformative; beta-catenin's specific complexes (catenin, TCF, destruction) are annotated separately.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic CC over-annotation.
- term:
    id: GO:0032993
    label: protein-DNA complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin is part of protein-DNA complexes only indirectly via TCF/LEF; the specific beta-catenin-TCF complex terms capture this better.
    action: KEEP_AS_NON_CORE
    reason: Indirect/over-general; electronic.
- term:
    id: GO:0033234
    label: negative regulation of protein sumoylation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Ortholog/electronic-inferred negative effect on SUMOylation; an indirect downstream activity unrelated to beta-catenin's core adhesion/Wnt functions.
    action: KEEP_AS_NON_CORE
    reason: SUMOylation suppression, electronic-inferred and indirect; non-core.
- term:
    id: GO:0034112
    label: positive regulation of homotypic cell-cell adhesion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Promotion of homotypic adhesion follows from beta-catenin's cadherin role, but the directional regulatory term is electronic and secondary to the structural terms.
    action: KEEP_AS_NON_CORE
    reason: Regulatory process; IEA/ISO.
- term:
    id: GO:0034333
    label: adherens junction assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: By linking cadherin to the catenin/actin machinery, beta-catenin is required for adherens junction assembly.
    action: ACCEPT
    reason: Core adhesion process; mechanistically central even if evidence is electronic/ISS.
- term:
    id: GO:0034394
    label: protein localization to cell surface
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin promotes surface delivery/retention of cadherin (e.g. via vinculin), a supporting trafficking role secondary to its structural function.
    action: KEEP_AS_NON_CORE
    reason: Peripheral process; electronic.
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin has been localized to the ciliary basal body, linking junction/centrosome pools; an electronically inferred location (IEA/ISO) peripheral to its core roles.
    action: KEEP_AS_NON_CORE
    reason: electronic minor localization, non-core
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: In some contexts beta-catenin promotes apoptosis; this electronic/ortholog-inferred bidirectional effect is a downstream consequence of context-specific transcription.
    action: KEEP_AS_NON_CORE
    reason: Context-dependent pro-apoptotic output downstream of transcription; non-core (electronic).
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin Wnt targets (e.g. survival genes) can suppress apoptosis; this electronic/ortholog-inferred pro-survival effect is downstream of transcription.
    action: KEEP_AS_NON_CORE
    reason: Anti-apoptotic effect downstream of Wnt-target gene expression; non-core (electronic).
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'Core to beta-catenin level control: phosphorylated beta-catenin is the SUBSTRATE ubiquitinated by SCF(BTRC) and degraded by the proteasome, the switch that gates Wnt signaling.'
    action: ACCEPT
    reason: Defining degradation process that regulates beta-catenin abundance.
    supported_by:
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research-falcon.md
      supporting_text: enabling recognition by **Ξ²-TrCP** (E3 ligase adaptor), ubiquitination, and proteasomal degradation
- term:
    id: GO:0043525
    label: positive regulation of neuron apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Ortholog-inferred pro-apoptotic effect on neurons in particular contexts, downstream of beta-catenin's transcriptional program.
    action: KEEP_AS_NON_CORE
    reason: Context-specific neuronal apoptosis downstream of Wnt transcription; non-core (electronic).
- term:
    id: GO:0044325
    label: transmembrane transporter binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Binding to transmembrane transporters/channels (e.g. TRPV4, SLC30A9) reflects context-specific interactions peripheral to core functions.
    action: KEEP_AS_NON_CORE
    reason: Specific peripheral partner class; electronic.
- term:
    id: GO:0044331
    label: cell-cell adhesion mediated by cadherin
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin mediates cadherin-dependent cell-cell adhesion, the precise process matching its molecular role.
    action: ACCEPT
    reason: Core, mechanistically specific adhesion term.
- term:
    id: GO:0045294
    label: alpha-catenin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Beta-catenin binds alpha-catenin via its N-terminal region, the key linkage coupling the cadherin-catenin complex to the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural MF; crystallographically defined, IPI/IDA.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: beta-catenin can repress specific targets (e.g. via SOX9/TCF competition or unliganded-TCF contexts), but its core, defining transcriptional role is positive coactivation of TCF/LEF targets.
    action: KEEP_AS_NON_CORE
    reason: Context-dependent repression; secondary to its activating role.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
    action: MODIFY
    reason: Generic parent; specialize to Pol II-specific positive regulation.
    proposed_replacement_terms: *id002
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
- term:
    id: GO:0046332
    label: SMAD binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: SMAD binding represents BMP/TGF-beta pathway crosstalk, secondary to beta-catenin's cadherin-adhesion and Wnt/TCF core functions.
    action: KEEP_AS_NON_CORE
    reason: Crosstalk; electronic (IEA/ISO) and not a core partner class.
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: A perinuclear cytoplasmic pool may reflect shuttling/staging intermediates, secondary to functional junctional and nuclear pools.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization; electronic.
- term:
    id: GO:0048660
    label: regulation of smooth muscle cell proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Modulation of vascular/visceral smooth muscle proliferation reflects Wnt/beta-catenin mitogenic target genes; ortholog/electronic-inferred downstream process.
    action: KEEP_AS_NON_CORE
    reason: Downstream proliferative control via Wnt transcriptional targets; non-core.
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0060231
    label: mesenchymal to epithelial transition
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin contributes to MET through cadherin-junction assembly and Wnt transcriptional balance; a cell-state transition (electronic) downstream of its dual role.
    action: KEEP_AS_NON_CORE
    reason: electronic; downstream of junction/Wnt MET role
- term:
    id: GO:0061154
    label: endothelial tube morphogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin supports endothelial tube formation via junctional integrity and Wnt transcription; a vascular morphogenetic outcome (electronic) downstream of its dual role.
    action: KEEP_AS_NON_CORE
    reason: electronic; downstream of junction/Wnt vascular roles
- term:
    id: GO:0061629
    label: RNA polymerase II-specific DNA-binding transcription factor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin directly binds Pol II-specific DNA-binding transcription factors (TCF/LEF) to drive Wnt-responsive transcription.
    action: ACCEPT
    reason: Core Wnt coactivation; IDA-supported specific TF binding.
- term:
    id: GO:0070369
    label: beta-catenin-TCF7L2 complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin forms the specific transcriptional complex with TCF7L2/TCF4 that activates Wnt target genes.
    action: ACCEPT
    reason: Core Wnt effector complex (specific TCF member).
- term:
    id: GO:0070411
    label: I-SMAD binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Inhibitory-SMAD binding reflects TGF-beta/BMP crosstalk rather than the canonical cadherin or Wnt/TCF functions of beta-catenin.
    action: KEEP_AS_NON_CORE
    reason: Crosstalk binding; electronic (IEA/ISO) and peripheral to core roles.
- term:
    id: GO:0070602
    label: regulation of centromeric sister chromatid cohesion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: A reported beta-catenin role at centromeric cohesion is a moonlighting function separate from its Wnt/adhesion core; supported by IMP plus electronic inference.
    action: KEEP_AS_NON_CORE
    reason: Sister-chromatid cohesion moonlighting role; non-core to Wnt/adhesion.
- term:
    id: GO:0071363
    label: cellular response to growth factor stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin participates in growth-factor-responsive transcription via Wnt crosstalk; a broad, electronically inferred response, kept as non-core given indirect linkage.
    action: KEEP_AS_NON_CORE
    reason: electronic/generic; indirect crosstalk, not core
- term:
    id: GO:0071681
    label: cellular response to indole-3-methanol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: No credible biological basis for beta-catenin as a responder to indole-3-methanol; an electronically propagated (IEA/ISO/ISS) annotation with no support.
    action: REMOVE
    reason: electronic annotation biologically unsupported for this gene
- term:
    id: GO:0071944
    label: cell periphery
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin localizes to the cell periphery at adherens junctions linking cadherins to actin; a broad location term consistent with its structural role but less specific than the junction terms.
    action: KEEP_AS_NON_CORE
    reason: electronic broad location subsumed by adherens-junction terms
- term:
    id: GO:0072497
    label: mesenchymal stem cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin directs MSC lineage choice (osteo/chondro/adipo) via Wnt/TCF transcription; a stem-cell fate outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven MSC differentiation
- term:
    id: GO:0090279
    label: regulation of calcium ion import
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Ortholog/electronic-inferred influence on calcium import, distinct from beta-catenin's core Wnt/adhesion roles; a downstream/indirect effect.
    action: KEEP_AS_NON_CORE
    reason: Calcium-import regulation, electronic-inferred and indirect; non-core.
- term:
    id: GO:0140297
    label: DNA-binding transcription factor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin binds TCF/LEF DNA-binding transcription factors to coactivate Wnt target genes; core to its nuclear Wnt-effector role.
    action: ACCEPT
    reason: 'Core Wnt: direct TCF/LEF coactivation (IPI); foundational MF for the transcriptional arm.'
- term:
    id: GO:1905555
    label: positive regulation of blood vessel branching
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin Wnt signaling promotes endothelial branching morphogenesis via target-gene expression; ortholog-inferred downstream vascular process.
    action: KEEP_AS_NON_CORE
    reason: Vessel branching is downstream of Wnt/beta-catenin endothelial transcription.
- term:
    id: GO:1990138
    label: neuron projection extension
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Ortholog/electronic-inferred role in axon/dendrite outgrowth, plausibly via cadherin-junction and Wnt-transcriptional inputs; a downstream neuronal phenotype.
    action: KEEP_AS_NON_CORE
    reason: Neurite extension downstream of adhesion/Wnt roles; non-core (electronic).
- term:
    id: GO:1990907
    label: beta-catenin-TCF complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: The nuclear beta-catenin-TCF complex is the central transcriptional effector unit of canonical Wnt signaling.
    action: ACCEPT
    reason: Core Wnt effector complex; IDA-supported.
- term:
    id: GO:2000008
    label: regulation of protein localization to cell surface
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Beta-catenin modulates cadherin surface levels, a regulatory trafficking role secondary to its structural junction function.
    action: KEEP_AS_NON_CORE
    reason: Peripheral regulatory process; electronic.
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:12408825
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:12408825
      supporting_text: ICAT inhibits beta-catenin binding to Tcf/Lef-family transcription factors and the general coactivator p300 using independent structural modules.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:10898789
  review:
    summary: An IDA call; beta-catenin represses certain Pol II targets in specific contexts, but this should be downgraded relative to its core activating coactivator role, not removed.
    action: KEEP_AS_NON_CORE
    reason: Experimental (IDA); downgrade context-specific repression, do not REMOVE.
    supported_by:
    - reference_id: PMID:10898789
      supporting_text: ICAT repressed the activity of the reporter gene in both cell lines in a dose-dependent manner
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:16936075
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:16936075
      supporting_text: The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 expression during somitogenesis.
- term:
    id: GO:0045597
    label: positive regulation of cell differentiation
  evidence_type: NAS
  original_reference_id: PMID:24847765
  review:
    summary: NAS-supported broad pro-differentiation role reflecting beta-catenin Wnt-driven fate gene activation; a downstream, non-specific process.
    action: KEEP_AS_NON_CORE
    reason: Umbrella pro-differentiation downstream of Wnt transcription (NAS).
    supported_by:
    - reference_id: PMID:24847765
      supporting_text: From inception to output, Tcf1 and Lef1 safeguard development of T cells and innate immune cells.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:16936075
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
    supported_by:
    - reference_id: PMID:16936075
      supporting_text: The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 expression during somitogenesis.
- term:
    id: GO:0050767
    label: regulation of neurogenesis
  evidence_type: NAS
  original_reference_id: PMID:23377854
  review:
    summary: NAS-supported broad neurogenesis regulation reflecting beta-catenin's Wnt control of neural progenitor fate/proliferation; a downstream umbrella process.
    action: KEEP_AS_NON_CORE
    reason: Umbrella neurogenesis regulation downstream of Wnt transcription (NAS).
    supported_by:
    - reference_id: PMID:23377854
      supporting_text: Physiological role of Ξ²-catenin/TCF signaling in neurons of the adult brain.
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:16936075
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:16936075
      supporting_text: The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 expression during somitogenesis.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0090090
    label: negative regulation of canonical Wnt signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:10898789
  review:
    summary: IDA-supported feedback/auto-regulatory role (e.g. via SOX9-mediated degradation, Axin2 induction); real but a regulatory facet rather than the core effector function.
    action: KEEP_AS_NON_CORE
    reason: Feedback regulation of its own pathway; non-core regulatory facet.
    supported_by:
    - reference_id: PMID:10898789
      supporting_text: Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein.
- term:
    id: GO:0090575
    label: RNA polymerase II transcription regulator complex
  evidence_type: IPI
  original_reference_id: PMID:21075118
  review:
    summary: As a TCF/LEF coactivator beta-catenin is a component of Pol II transcription regulator complexes on Wnt target promoters.
    action: ACCEPT
    reason: Core nuclear Wnt effector; IPI-supported complex membership.
    supported_by:
    - reference_id: PMID:21075118
      supporting_text: Biochemical and structural characterization of Ξ²-catenin interactions with nonphosphorylated and CK2-phosphorylated Lef-1.
- term:
    id: GO:1990711
    label: beta-catenin-ICAT complex
  evidence_type: IPI
  original_reference_id: PMID:10898789
  review:
    summary: ICAT (CTNNBIP1) binding sequesters beta-catenin from TCF/p300, an inhibitory complex regulating signaling rather than a core effector assembly.
    action: KEEP_AS_NON_CORE
    reason: Inhibitory regulatory complex; IPI but peripheral.
    supported_by:
    - reference_id: PMID:10898789
      supporting_text: Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein.
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:12494996
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:12494996
      supporting_text: Loss of desmoglein 2 suggests essential functions for early embryonic development and proliferation of embryonal stem cells.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0010717
    label: regulation of epithelial to mesenchymal transition
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Generic EMT regulation reflects beta-catenin's dual junctional and Wnt-transcriptional control of epithelial plasticity; an electronic/ortholog-inferred downstream process.
    action: KEEP_AS_NON_CORE
    reason: Downstream EMT control via Wnt transcription and cadherin-adhesion balance; non-core.
- term:
    id: GO:0060231
    label: mesenchymal to epithelial transition
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Beta-catenin contributes to MET through cadherin-junction assembly and Wnt transcriptional balance; a cell-state transition (electronic) downstream of its dual role.
    action: KEEP_AS_NON_CORE
    reason: electronic; downstream of junction/Wnt MET role
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: IDA
  original_reference_id: PMID:22723415
  review:
    summary: 'The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.'
    action: ACCEPT
    reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
    supported_by:
    - reference_id: PMID:22723415
      supporting_text: Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:22723415
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
    supported_by:
    - reference_id: PMID:22723415
      supporting_text: Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
- term:
    id: GO:1990226
    label: histone methyltransferase binding
  evidence_type: IPI
  original_reference_id: PMID:22723415
  review:
    summary: Beta-catenin can recruit chromatin-modifying machinery (e.g. SET/MLL methyltransferases) to Wnt targets, a coactivator-associated but specialized interaction.
    action: KEEP_AS_NON_CORE
    reason: Specific partner binding; IPI, peripheral.
    supported_by:
    - reference_id: PMID:22723415
      supporting_text: Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:27375112
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:27375112
      supporting_text: Antagonistic Regulation of Intercellular Cohesion by Plakophilins 1 and 3.
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:27375112
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:27375112
      supporting_text: Antagonistic Regulation of Intercellular Cohesion by Plakophilins 1 and 3.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:27015268
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:27015268
      supporting_text: Plakophilin-1, a Novel Wnt Signaling Regulator, Is Critical for Tooth Development and Ameloblast Differentiation.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:27015268
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:27015268
      supporting_text: Plakophilin-1, a Novel Wnt Signaling Regulator, Is Critical for Tooth Development and Ameloblast Differentiation.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:27015268
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
    supported_by:
    - reference_id: PMID:27015268
      supporting_text: Plakophilin-1, a Novel Wnt Signaling Regulator, Is Critical for Tooth Development and Ameloblast Differentiation.
- term:
    id: GO:0042734
    label: presynaptic membrane
  evidence_type: IDA
  original_reference_id: PMID:8909549
  review:
    summary: A presynaptic-membrane pool reflects synaptic cadherin adhesion, secondary to core junctional localization.
    action: KEEP_AS_NON_CORE
    reason: Synapse-specific; IDA, non-core.
    supported_by:
    - reference_id: PMID:8909549
      supporting_text: The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones.
- term:
    id: GO:0045211
    label: postsynaptic membrane
  evidence_type: IDA
  original_reference_id: PMID:8909549
  review:
    summary: A postsynaptic-membrane pool supports synaptic cadherin adhesion in neurons, a tissue-specific localization.
    action: KEEP_AS_NON_CORE
    reason: Synapse-specific; IDA, non-core.
    supported_by:
    - reference_id: PMID:8909549
      supporting_text: The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones.
- term:
    id: GO:0051963
    label: regulation of synapse assembly
  evidence_type: IMP
  original_reference_id: PMID:28641114
  review:
    summary: Beta-catenin regulates synapse assembly via cadherin adhesion in neurons, a tissue-specific role distinct from core epithelial functions.
    action: KEEP_AS_NON_CORE
    reason: Neuronal process; IDA/IMP, non-core.
    supported_by:
    - reference_id: PMID:28641114
      supporting_text: A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Complexes in Stabilizing Spines and Functional Synapses in the Neocortex.
- term:
    id: GO:0051963
    label: regulation of synapse assembly
  evidence_type: IDA
  original_reference_id: PMID:28641114
  review:
    summary: Beta-catenin regulates synapse assembly via cadherin adhesion in neurons, a tissue-specific role distinct from core epithelial functions.
    action: KEEP_AS_NON_CORE
    reason: Neuronal process; IDA/IMP, non-core.
    supported_by:
    - reference_id: PMID:28641114
      supporting_text: A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Complexes in Stabilizing Spines and Functional Synapses in the Neocortex.
- term:
    id: GO:0097091
    label: synaptic vesicle clustering
  evidence_type: IMP
  original_reference_id: PMID:14622577
  review:
    summary: Beta-catenin organizes presynaptic vesicle clustering through cadherin-junction scaffolding at synapses; a downstream adhesion-linked synaptic role.
    action: KEEP_AS_NON_CORE
    reason: Vesicle clustering downstream of cadherin-adhesion scaffolding role.
    supported_by:
    - reference_id: PMID:14622577
      supporting_text: Role of beta-catenin in synaptic vesicle localization and presynaptic assembly.
- term:
    id: GO:0097091
    label: synaptic vesicle clustering
  evidence_type: IDA
  original_reference_id: PMID:14622577
  review:
    summary: Beta-catenin organizes presynaptic vesicle clustering through cadherin-junction scaffolding at synapses; a downstream adhesion-linked synaptic role.
    action: KEEP_AS_NON_CORE
    reason: Vesicle clustering downstream of cadherin-adhesion scaffolding role.
    supported_by:
    - reference_id: PMID:14622577
      supporting_text: Role of beta-catenin in synaptic vesicle localization and presynaptic assembly.
- term:
    id: GO:0098685
    label: Schaffer collateral - CA1 synapse
  evidence_type: IMP
  original_reference_id: PMID:14622577
  review:
    summary: Beta-catenin localizes to specific hippocampal CA1 synapses where it organizes synaptic adhesion, a tissue-restricted role distinct from its core junction/Wnt functions.
    action: KEEP_AS_NON_CORE
    reason: Synapse-specific neuronal localization; real (IDA/IMP) but peripheral.
    supported_by:
    - reference_id: PMID:14622577
      supporting_text: Role of beta-catenin in synaptic vesicle localization and presynaptic assembly.
- term:
    id: GO:0098685
    label: Schaffer collateral - CA1 synapse
  evidence_type: IDA
  original_reference_id: PMID:14622577
  review:
    summary: Beta-catenin localizes to specific hippocampal CA1 synapses where it organizes synaptic adhesion, a tissue-restricted role distinct from its core junction/Wnt functions.
    action: KEEP_AS_NON_CORE
    reason: Synapse-specific neuronal localization; real (IDA/IMP) but peripheral.
    supported_by:
    - reference_id: PMID:14622577
      supporting_text: Role of beta-catenin in synaptic vesicle localization and presynaptic assembly.
- term:
    id: GO:0098831
    label: presynaptic active zone cytoplasmic component
  evidence_type: IDA
  original_reference_id: PMID:8909549
  review:
    summary: Beta-catenin (with Scrib) localizes to the presynaptic active zone organizing vesicle clustering, a specialized neuronal role.
    action: KEEP_AS_NON_CORE
    reason: Synapse-specific localization; IDA, non-core.
    supported_by:
    - reference_id: PMID:8909549
      supporting_text: The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones.
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: IMP
  original_reference_id: PMID:28641114
  review:
    summary: Beta-catenin localizes to glutamatergic synapses where cadherin adhesion organizes synaptic structure, a neuron-specific role.
    action: KEEP_AS_NON_CORE
    reason: Synapse-specific localization; IDA/IMP, non-core.
    supported_by:
    - reference_id: PMID:28641114
      supporting_text: A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Complexes in Stabilizing Spines and Functional Synapses in the Neocortex.
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: IDA
  original_reference_id: PMID:28641114
  review:
    summary: Beta-catenin localizes to glutamatergic synapses where cadherin adhesion organizes synaptic structure, a neuron-specific role.
    action: KEEP_AS_NON_CORE
    reason: Synapse-specific localization; IDA/IMP, non-core.
    supported_by:
    - reference_id: PMID:28641114
      supporting_text: A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Complexes in Stabilizing Spines and Functional Synapses in the Neocortex.
- term:
    id: GO:0099092
    label: postsynaptic density, intracellular component
  evidence_type: IDA
  original_reference_id: PMID:8909549
  review:
    summary: Beta-catenin localizes to the postsynaptic density via cadherin-based synaptic adhesion; a localization reflecting its adhesion/scaffolding role rather than Wnt signaling.
    action: KEEP_AS_NON_CORE
    reason: PSD localization via cadherin adhesion role; non-core component annotation.
    supported_by:
    - reference_id: PMID:8909549
      supporting_text: The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones.
- term:
    id: GO:0048568
    label: embryonic organ development
  evidence_type: IMP
  original_reference_id: PMID:30478225
  review:
    summary: Broad embryonic-organ umbrella conveying nothing beta-catenin-specific; the many specific organ terms already capture its Wnt-driven developmental roles.
    action: MARK_AS_OVER_ANNOTATED
    reason: vague umbrella superseded by specific organ terms
    supported_by:
    - reference_id: PMID:30478225
      supporting_text: TBX2 and TBX3 act downstream of canonical WNT signaling in patterning and differentiation of the mouse ureteric mesenchyme.
- term:
    id: GO:0072497
    label: mesenchymal stem cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:30478225
  review:
    summary: Beta-catenin directs MSC lineage choice (osteo/chondro/adipo) via Wnt/TCF transcription; a stem-cell fate outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven MSC differentiation
    supported_by:
    - reference_id: PMID:30478225
      supporting_text: TBX2 and TBX3 act downstream of canonical WNT signaling in patterning and differentiation of the mouse ureteric mesenchyme.
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: IDA
  original_reference_id: PMID:15905404
  review:
    summary: 'The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.'
    action: ACCEPT
    reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
    supported_by:
    - reference_id: PMID:15905404
      supporting_text: Functional interaction between beta-catenin and FOXO in oxidative stress signaling.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0036520
    label: astrocyte-dopaminergic neuron signaling
  evidence_type: IMP
  original_reference_id: PMID:21752258
  review:
    summary: Beta-catenin contributes to astrocyte-dopaminergic neuron crosstalk supporting midbrain DA neurogenesis; a niche-signaling outcome downstream of Wnt transcription.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt role in DA neuron niche signaling
    supported_by:
    - reference_id: PMID:21752258
      supporting_text: 'A Wnt1 regulated Frizzled-1/Ξ²-Catenin signaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: Therapeutical relevance for neuron survival and neuroprotection.'
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:19122665
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:19122665
      supporting_text: Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:21752258
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:21752258
      supporting_text: 'A Wnt1 regulated Frizzled-1/Ξ²-Catenin signaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: Therapeutical relevance for neuron survival and neuroprotection.'
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:22723415
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:22723415
      supporting_text: Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0003151
    label: outflow tract morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:12464179
  review:
    summary: Beta-catenin Wnt signaling in second-heart-field/neural-crest shapes the cardiac outflow tract; a downstream cardiac-morphogenesis phenotype.
    action: KEEP_AS_NON_CORE
    reason: Outflow tract morphogenesis downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:12464179
      supporting_text: Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IMP
  original_reference_id: PMID:12464179
  review:
    summary: Beta-catenin drives proliferation via Wnt mitogenic targets (Myc, cyclin D1); a key but downstream consequence of its transcriptional coactivation.
    action: KEEP_AS_NON_CORE
    reason: Proliferation downstream of Wnt target genes Myc/CcnD1; non-core.
    supported_by:
    - reference_id: PMID:12464179
      supporting_text: Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.
- term:
    id: GO:1901331
    label: positive regulation of odontoblast differentiation
  evidence_type: IMP
  original_reference_id: PMID:29148101
  review:
    summary: Beta-catenin promotes odontoblast differentiation via Wnt-target transcription in dental mesenchyme; a downstream lineage phenotype.
    action: KEEP_AS_NON_CORE
    reason: Odontoblast differentiation downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:29148101
      supporting_text: Homeobox protein MSX-1 inhibits expression of bone morphogenetic protein 2, bone morphogenetic protein 4, and lymphoid enhancer-binding factor 1 via Wnt/Ξ²-catenin signaling to prevent differentiation of dental mesenchymal cells during the late bell stage.
- term:
    id: GO:1903377
    label: negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:21752258
  review:
    summary: Beta-catenin attenuates oxidative-stress-triggered neuronal intrinsic apoptosis, likely through Wnt survival-gene output; a specific stress-protection phenotype.
    action: KEEP_AS_NON_CORE
    reason: Stress-specific neuroprotection downstream of Wnt transcription; non-core.
    supported_by:
    - reference_id: PMID:21752258
      supporting_text: 'A Wnt1 regulated Frizzled-1/Ξ²-Catenin signaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: Therapeutical relevance for neuron survival and neuroprotection.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32533114
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:32533114
      supporting_text: ADNP promotes neural differentiation by modulating Wnt/Ξ²-catenin signaling.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:16678101
  review:
    summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
    action: ACCEPT
    reason: Core nuclear Wnt role; IDA/IGI-supported.
    supported_by:
    - reference_id: PMID:16678101
      supporting_text: Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:16818445
  review:
    summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
    action: ACCEPT
    reason: Core nuclear Wnt role; IDA/IGI-supported.
    supported_by:
    - reference_id: PMID:16818445
      supporting_text: Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:17767158
  review:
    summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
    action: ACCEPT
    reason: Core nuclear Wnt role; IDA/IGI-supported.
    supported_by:
    - reference_id: PMID:17767158
      supporting_text: Modulation of morphogenesis by noncanonical Wnt signaling requires ATF/CREB family-mediated transcriptional activation of TGFbeta2.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:19619491
  review:
    summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
    action: ACCEPT
    reason: Core nuclear Wnt role; IDA/IGI-supported.
    supported_by:
    - reference_id: PMID:19619491
      supporting_text: Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:19620969
  review:
    summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
    action: ACCEPT
    reason: Core nuclear Wnt role; IDA/IGI-supported.
    supported_by:
    - reference_id: PMID:19620969
      supporting_text: A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:19690384
  review:
    summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
    action: ACCEPT
    reason: Core nuclear Wnt role; IDA/IGI-supported.
    supported_by:
    - reference_id: PMID:19690384
      supporting_text: Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:20159597
  review:
    summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
    action: ACCEPT
    reason: Core nuclear Wnt role; IDA/IGI-supported.
    supported_by:
    - reference_id: PMID:20159597
      supporting_text: Characterization and in vivo pharmacological rescue of a Wnt2-Gata6 pathway required for cardiac inflow tract development.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:21350016
  review:
    summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
    action: ACCEPT
    reason: Core nuclear Wnt role; IDA/IGI-supported.
    supported_by:
    - reference_id: PMID:21350016
      supporting_text: Canonical Wnt9b signaling balances progenitor cell expansion and differentiation during kidney development.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:21512031
  review:
    summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
    action: ACCEPT
    reason: Core nuclear Wnt role; IDA/IGI-supported.
    supported_by:
    - reference_id: PMID:21512031
      supporting_text: Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IGI
  original_reference_id: PMID:23824574
  review:
    summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
    action: ACCEPT
    reason: Core nuclear Wnt role; IDA/IGI-supported.
    supported_by:
    - reference_id: PMID:23824574
      supporting_text: Wnt/Ξ²-catenin signalling regulates Sox17 expression and is essential for organizer and endoderm formation in the mouse.
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: IDA
  original_reference_id: PMID:12235125
  review:
    summary: 'The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.'
    action: ACCEPT
    reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
    supported_by:
    - reference_id: PMID:12235125
      supporting_text: Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: IDA
  original_reference_id: PMID:12464179
  review:
    summary: 'The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.'
    action: ACCEPT
    reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
    supported_by:
    - reference_id: PMID:12464179
      supporting_text: Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: IDA
  original_reference_id: PMID:16678101
  review:
    summary: 'The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.'
    action: ACCEPT
    reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
    supported_by:
    - reference_id: PMID:16678101
      supporting_text: Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: IDA
  original_reference_id: PMID:19056892
  review:
    summary: 'The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.'
    action: ACCEPT
    reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
    supported_by:
    - reference_id: PMID:19056892
      supporting_text: A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: IMP
  original_reference_id: PMID:19619491
  review:
    summary: 'The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.'
    action: ACCEPT
    reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
    supported_by:
    - reference_id: PMID:19619491
      supporting_text: Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10318824
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:10318824
      supporting_text: Functional domains of axin. Importance of the C terminus as an oligomerization domain.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11104755
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:11104755
      supporting_text: Substitution of a glycogen synthase kinase-3beta phosphorylation site in presenilin 1 separates presenilin function from beta-catenin signaling.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12432063
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:12432063
      supporting_text: Protein kinase CKII regulates the interaction of beta-catenin with alpha-catenin and its protein stability.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12695331
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:12695331
      supporting_text: NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12861022
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:12861022
      supporting_text: T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14647292
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:14647292
      supporting_text: Mammalian formin-1 participates in adherens junctions and polymerization of linear actin cables.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14960280
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:14960280
      supporting_text: Ozz-E3, a muscle-specific ubiquitin ligase, regulates beta-catenin degradation during myogenesis.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15574752
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:15574752
      supporting_text: Role of a BCL9-related beta-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15781477
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:15781477
      supporting_text: Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15834408
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:15834408
      supporting_text: The KIF3 motor transports N-cadherin and organizes the developing neuroepithelium.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16368433
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:16368433
      supporting_text: Deficient E-cadherin adhesion in C57BL/6J-Min/+ mice is associated with increased tyrosine kinase activity and RhoA-dependent actomyosin contractility.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17535849
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:17535849
      supporting_text: A unique and specific interaction between alphaT-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18202148
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:18202148
      supporting_text: Cooperative control via lymphoid enhancer factor 1/T cell factor 3 and estrogen receptor-alpha for uterine gene regulation by estrogen.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18632848
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:18632848
      supporting_text: SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19503085
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:19503085
      supporting_text: HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19725955
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:19725955
      supporting_text: Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21512031
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:21512031
      supporting_text: Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22665494
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:22665494
      supporting_text: mrhl RNA, a long noncoding RNA, negatively regulates Wnt signaling through its protein partner Ddx5/p68 in mouse spermatogonial cells.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26787558
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:26787558
      supporting_text: SPECC1L deficiency results in increased adherens junction stability and reduced cranial neural crest cell delamination.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30659184
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:30659184
      supporting_text: Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8555428
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:8555428
      supporting_text: Immunotoxicologic effects of ethylene dibromide in the mouse and their modulation by the estrous cycle.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9488439
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:9488439
      supporting_text: Two members of the Tcf family implicated in Wnt/beta-catenin signaling during embryogenesis in the mouse.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9554852
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:9554852
      supporting_text: Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IPI
  original_reference_id: PMID:30659184
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:30659184
      supporting_text: Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:11731231
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:11731231
      supporting_text: Dynamic expression and nuclear accumulation of beta-catenin during the development of hair follicle-derived structures.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:11731265
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:11731265
      supporting_text: Expression of Tcf/Lef and sFrp and localization of beta-catenin in the developing mouse lung.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:11872843
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:11872843
      supporting_text: Colorectal cancer in mice genetically deficient in the mucin Muc2.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:12874278
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:12874278
      supporting_text: The PDZ protein tax-interacting protein-1 inhibits beta-catenin transcriptional activity and growth of colorectal cancer cells.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:12885771
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:12885771
      supporting_text: beta-Catenin is required for specification of proximal/distal cell fate during lung morphogenesis.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:12923052
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:12923052
      supporting_text: Genetic interaction between Wnt/beta-catenin and BMP receptor signaling during formation of the AER and the dorsal-ventral axis in the limb.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:15371327
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:15371327
      supporting_text: Wnt/beta-catenin signaling is sufficient and necessary for synovial joint formation.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:15574752
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:15574752
      supporting_text: Role of a BCL9-related beta-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:15778706
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:15778706
      supporting_text: Wnt signalling induces maturation of Paneth cells in intestinal crypts.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:15866163
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:15866163
      supporting_text: Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:15866165
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:15866165
      supporting_text: Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:16439479
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:16439479
      supporting_text: Foxf1 and Foxf2 control murine gut development by limiting mesenchymal Wnt signaling and promoting extracellular matrix production.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:16489008
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:16489008
      supporting_text: Patched1 functions as a gatekeeper by promoting cell cycle progression.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:16678815
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:16678815
      supporting_text: Lef1 is required for the transition of Wnt signaling from mesenchymal to epithelial cells in the mouse embryonic mammary gland.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:16858399
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:16858399
      supporting_text: C3G regulates the size of the cerebral cortex neural precursor population.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:16989802
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:16989802
      supporting_text: Levels of mesenchymal FGFR2 signaling modulate smooth muscle progenitor cell commitment in the lung.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:17128274
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:17128274
      supporting_text: Wnt-beta-catenin signaling initiates taste papilla development.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:17560563
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:17560563
      supporting_text: Fgf10 dosage is critical for the amplification of epithelial cell progenitors and for the formation of multiple mesenchymal lineages during lung development.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:17596282
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:17596282
      supporting_text: Unique mechanisms of growth regulation and tumor suppression upon Apc inactivation in the pancreas.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:17615359
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:17615359
      supporting_text: Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:18978355
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:18978355
      supporting_text: Overexpression of TEAD-1 in transgenic mouse striated muscles produces a slower skeletal muscle contractile phenotype.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:19213727
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:19213727
      supporting_text: Wnt11 promotes osteoblast maturation and mineralization through R-spondin 2.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:19497282
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:19497282
      supporting_text: Wnt7a activates the planar cell polarity pathway to drive the symmetric expansion of satellite stem cells.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:19796622
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:19796622
      supporting_text: Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:19850029
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:19850029
      supporting_text: A critical role for sFRP proteins in maintaining caudal neural tube closure in mice via inhibition of BMP signaling.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:21991325
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:21991325
      supporting_text: RSPO1/Ξ²-catenin signaling pathway regulates oogonia differentiation and entry into meiosis in the mouse fetal ovary.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:22665494
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:22665494
      supporting_text: mrhl RNA, a long noncoding RNA, negatively regulates Wnt signaling through its protein partner Ddx5/p68 in mouse spermatogonial cells.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:23266329
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:23266329
      supporting_text: Kruppel-like factor 5 controls villus formation and initiation of cytodifferentiation in the embryonic intestinal epithelium.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:23610556
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:23610556
      supporting_text: A positive feedback loop involving Gcm1 and Fzd5 directs chorionic branching morphogenesis in the placenta.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:23740243
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:23740243
      supporting_text: Activation of the transcription factor GLI1 by WNT signaling underlies the role of SULFATASE 2 as a regulator of tissue regeneration.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:25535395
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:25535395
      supporting_text: Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:30659184
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:30659184
      supporting_text: Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:31222549
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:31222549
      supporting_text: The Shisa3 knockout mouse exhibits normal bone phenotype.
- term:
    id: GO:0005667
    label: transcription regulator complex
  evidence_type: IDA
  original_reference_id: PMID:12464179
  review:
    summary: Beta-catenin is a component of transcription regulator complexes (with TCF/LEF and coactivators) that drive Wnt target gene expression.
    action: ACCEPT
    reason: Core nuclear Wnt effector complex; IDA-supported.
    supported_by:
    - reference_id: PMID:12464179
      supporting_text: Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.
- term:
    id: GO:0005667
    label: transcription regulator complex
  evidence_type: IDA
  original_reference_id: PMID:12861022
  review:
    summary: Beta-catenin is a component of transcription regulator complexes (with TCF/LEF and coactivators) that drive Wnt target gene expression.
    action: ACCEPT
    reason: Core nuclear Wnt effector complex; IDA-supported.
    supported_by:
    - reference_id: PMID:12861022
      supporting_text: T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors.
- term:
    id: GO:0005667
    label: transcription regulator complex
  evidence_type: IDA
  original_reference_id: PMID:16678101
  review:
    summary: Beta-catenin is a component of transcription regulator complexes (with TCF/LEF and coactivators) that drive Wnt target gene expression.
    action: ACCEPT
    reason: Core nuclear Wnt effector complex; IDA-supported.
    supported_by:
    - reference_id: PMID:16678101
      supporting_text: Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IPI
  original_reference_id: PMID:30659184
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:30659184
      supporting_text: Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:11731231
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:11731231
      supporting_text: Dynamic expression and nuclear accumulation of beta-catenin during the development of hair follicle-derived structures.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:11731265
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:11731265
      supporting_text: Expression of Tcf/Lef and sFrp and localization of beta-catenin in the developing mouse lung.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:12235125
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:12235125
      supporting_text: Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:12923052
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:12923052
      supporting_text: Genetic interaction between Wnt/beta-catenin and BMP receptor signaling during formation of the AER and the dorsal-ventral axis in the limb.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:14981260
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:14981260
      supporting_text: Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of beta-catenin.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:15525667
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:15525667
      supporting_text: Stabilization of beta-catenin in the mouse zygote leads to premature epithelial-mesenchymal transition in the epiblast.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:15574752
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:15574752
      supporting_text: Role of a BCL9-related beta-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:16489008
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:16489008
      supporting_text: Patched1 functions as a gatekeeper by promoting cell cycle progression.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:17128274
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:17128274
      supporting_text: Wnt-beta-catenin signaling initiates taste papilla development.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:19213727
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:19213727
      supporting_text: Wnt11 promotes osteoblast maturation and mineralization through R-spondin 2.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:30659184
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:30659184
      supporting_text: Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:12055200
  review:
    summary: Beta-catenin has a cytosolic pool subject to destruction-complex regulation and Wnt-dependent stabilization.
    action: ACCEPT
    reason: Genuine pool; IDA/TAS-supported.
    supported_by:
    - reference_id: PMID:12055200
      supporting_text: Regulation of Wnt signaling during adipogenesis.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:15673614
  review:
    summary: Beta-catenin has a cytosolic pool subject to destruction-complex regulation and Wnt-dependent stabilization.
    action: ACCEPT
    reason: Genuine pool; IDA/TAS-supported.
    supported_by:
    - reference_id: PMID:15673614
      supporting_text: Wnt10b deficiency promotes coexpression of myogenic and adipogenic programs in myoblasts.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:12040017
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
    supported_by:
    - reference_id: PMID:12040017
      supporting_text: 'Mouse mammary epithelial cells express the Na-K-Cl cotransporter, NKCC1: characterization, localization, and involvement in ductal development and morphogenesis.'
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:16418220
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
    supported_by:
    - reference_id: PMID:16418220
      supporting_text: Desmocollin 3 is required for pre-implantation development of the mouse embryo.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:16740478
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
    supported_by:
    - reference_id: PMID:16740478
      supporting_text: Apc tumor suppressor gene is the "zonation-keeper" of mouse liver.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:16858399
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
    supported_by:
    - reference_id: PMID:16858399
      supporting_text: C3G regulates the size of the cerebral cortex neural precursor population.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:16962386
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
    supported_by:
    - reference_id: PMID:16962386
      supporting_text: 'Tissue, cellular and sub-cellular localization of the Vangl2 protein during embryonic development: effect of the Lp mutation.'
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:17596282
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
    supported_by:
    - reference_id: PMID:17596282
      supporting_text: Unique mechanisms of growth regulation and tumor suppression upon Apc inactivation in the pancreas.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:19966784
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
    supported_by:
    - reference_id: PMID:19966784
      supporting_text: Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closure.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:23266329
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
    supported_by:
    - reference_id: PMID:23266329
      supporting_text: Kruppel-like factor 5 controls villus formation and initiation of cytodifferentiation in the embryonic intestinal epithelium.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:8853988
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
    supported_by:
    - reference_id: PMID:8853988
      supporting_text: Expression and cell membrane localization of catenins during mouse preimplantation development.
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: IDA
  original_reference_id: PMID:12181493
  review:
    summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
    action: ACCEPT
    reason: Core junctional localization; IDA.
    supported_by:
    - reference_id: PMID:12181493
      supporting_text: TCL1 participates in early embryonic development and is overexpressed in human seminomas.
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: IDA
  original_reference_id: PMID:14597196
  review:
    summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
    action: ACCEPT
    reason: Core junctional localization; IDA.
    supported_by:
    - reference_id: PMID:14597196
      supporting_text: Overexpression of Sonic Hedgehog suppresses embryonic hair follicle morphogenesis.
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: IDA
  original_reference_id: PMID:18816447
  review:
    summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
    action: ACCEPT
    reason: Core junctional localization; IDA.
    supported_by:
    - reference_id: PMID:18816447
      supporting_text: 'Diverse roles of E-cadherin in the morphogenesis of the submandibular gland: insights into the formation of acinar and ductal structures.'
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: ISO
  original_reference_id: PMID:19151727
  review:
    summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
    action: ACCEPT
    reason: Core junctional localization; IDA.
    supported_by:
    - reference_id: PMID:19151727
      supporting_text: Regulation of cardiovascular development and integrity by the heart of glass-cerebral cavernous malformation protein pathway.
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: IDA
  original_reference_id: PMID:20089884
  review:
    summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
    action: ACCEPT
    reason: Core junctional localization; IDA.
    supported_by:
    - reference_id: PMID:20089884
      supporting_text: Milk secretion and ejection are impaired in the mammary gland of mice harboring a Cx43 mutant while expression and localization of tight and adherens junction proteins remain unchanged.
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: IDA
  original_reference_id: PMID:21377456
  review:
    summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
    action: ACCEPT
    reason: Core junctional localization; IDA.
    supported_by:
    - reference_id: PMID:21377456
      supporting_text: Grainyhead-like 2 regulates neural tube closure and adhesion molecule expression during neural fold fusion.
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: IDA
  original_reference_id: PMID:24191021
  review:
    summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
    action: ACCEPT
    reason: Core junctional localization; IDA.
    supported_by:
    - reference_id: PMID:24191021
      supporting_text: Sox9 plays multiple roles in the lung epithelium during branching morphogenesis.
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: IDA
  original_reference_id: PMID:9950951
  review:
    summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
    action: ACCEPT
    reason: Core junctional localization; IDA.
    supported_by:
    - reference_id: PMID:9950951
      supporting_text: Nuclear localization of beta-catenin and loss of apical brush border actin in cystic tubules of bcl-2 -/- mice.
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:11731229
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:11731229
      supporting_text: FAM deubiquitylating enzyme is essential for preimplantation mouse embryo development.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:12203715
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:12203715
      supporting_text: Localization of the novel Xin protein to the adherens junction complex in cardiac and skeletal muscle during development.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:12695331
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:12695331
      supporting_text: NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:14657280
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:14657280
      supporting_text: 'Lamellipodium extension and cadherin adhesion: two cell responses to cadherin activation relying on distinct signalling pathways.'
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:15148305
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:15148305
      supporting_text: Mammalian Fat1 cadherin regulates actin dynamics and cell-cell contact.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:15292239
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:15292239
      supporting_text: Defects in cell adhesion and the visceral endoderm following ablation of nonmuscle myosin heavy chain II-A in mice.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:15645444
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:15645444
      supporting_text: Gene expression profile analysis of mouse colon embryonic development.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:15775979
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:15775979
      supporting_text: E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:16199027
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:16199027
      supporting_text: Vezatin, a protein associated to adherens junctions, is required for mouse blastocyst morphogenesis.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:16892058
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:16892058
      supporting_text: The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:17544522
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:17544522
      supporting_text: Targeted disruption of the murine large nuclear KIAA1440/Ints1 protein causes growth arrest in early blastocyst stage embryos and eventual apoptotic cell death.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:21991385
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:21991385
      supporting_text: Adhesion protein VSIG1 is required for the proper differentiation of glandular gastric epithelia.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:23824574
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:23824574
      supporting_text: Wnt/Ξ²-catenin signalling regulates Sox17 expression and is essential for organizer and endoderm formation in the mouse.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:26787558
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:26787558
      supporting_text: SPECC1L deficiency results in increased adherens junction stability and reduced cranial neural crest cell delamination.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:29211732
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:29211732
      supporting_text: The mouse Jhy gene regulates ependymal cell differentiation and ciliogenesis.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005916
    label: fascia adherens
  evidence_type: IDA
  original_reference_id: PMID:16481394
  review:
    summary: Beta-catenin is a core structural component of the fascia adherens, linking N-cadherin to actin at cardiac intercalated-disc junctions (IDA); a direct adhesion-structure localization.
    action: ACCEPT
    reason: direct structural localization at adherens junction
    supported_by:
    - reference_id: PMID:16481394
      supporting_text: 'The transitional junction: a new functional subcellular domain at the intercalated disc.'
- term:
    id: GO:0005923
    label: bicellular tight junction
  evidence_type: IDA
  original_reference_id: PMID:17130295
  review:
    summary: Beta-catenin is detected near tight junctions through junctional crosstalk, but tight junctions are not its primary structural site (adherens junctions are).
    action: KEEP_AS_NON_CORE
    reason: Adjacent-junction localization; IDA but non-core.
    supported_by:
    - reference_id: PMID:17130295
      supporting_text: Distinct subdomain organization and molecular composition of a tight junction with adherens junction features.
- term:
    id: GO:0014704
    label: intercalated disc
  evidence_type: IDA
  original_reference_id: PMID:17535849
  review:
    summary: Beta-catenin is a core structural component of the cardiac intercalated disc, anchoring N-cadherin to the actin cytoskeleton (IDA/ISO); a direct adhesion-structure localization.
    action: ACCEPT
    reason: direct structural localization at cardiac junction
    supported_by:
    - reference_id: PMID:17535849
      supporting_text: A unique and specific interaction between alphaT-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:11731231
  review:
    summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
    action: KEEP_AS_NON_CORE
    reason: Over-general CC parent.
    supported_by:
    - reference_id: PMID:11731231
      supporting_text: Dynamic expression and nuclear accumulation of beta-catenin during the development of hair follicle-derived structures.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:12055200
  review:
    summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
    action: KEEP_AS_NON_CORE
    reason: Over-general CC parent.
    supported_by:
    - reference_id: PMID:12055200
      supporting_text: Regulation of Wnt signaling during adipogenesis.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:12432063
  review:
    summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
    action: KEEP_AS_NON_CORE
    reason: Over-general CC parent.
    supported_by:
    - reference_id: PMID:12432063
      supporting_text: Protein kinase CKII regulates the interaction of beta-catenin with alpha-catenin and its protein stability.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:12611902
  review:
    summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
    action: KEEP_AS_NON_CORE
    reason: Over-general CC parent.
    supported_by:
    - reference_id: PMID:12611902
      supporting_text: Regulation of the SHP-2 tyrosine phosphatase by a novel cholesterol- and cell confluence-dependent mechanism.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:14657280
  review:
    summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
    action: KEEP_AS_NON_CORE
    reason: Over-general CC parent.
    supported_by:
    - reference_id: PMID:14657280
      supporting_text: 'Lamellipodium extension and cadherin adhesion: two cell responses to cadherin activation relying on distinct signalling pathways.'
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:15987773
  review:
    summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
    action: KEEP_AS_NON_CORE
    reason: Over-general CC parent.
    supported_by:
    - reference_id: PMID:15987773
      supporting_text: Forkhead box A1 regulates prostate ductal morphogenesis and promotes epithelial cell maturation.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:16364283
  review:
    summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
    action: KEEP_AS_NON_CORE
    reason: Over-general CC parent.
    supported_by:
    - reference_id: PMID:16364283
      supporting_text: Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:21991325
  review:
    summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
    action: KEEP_AS_NON_CORE
    reason: Over-general CC parent.
    supported_by:
    - reference_id: PMID:21991325
      supporting_text: RSPO1/Ξ²-catenin signaling pathway regulates oogonia differentiation and entry into meiosis in the mouse fetal ovary.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:22139371
  review:
    summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
    action: KEEP_AS_NON_CORE
    reason: Over-general CC parent.
    supported_by:
    - reference_id: PMID:22139371
      supporting_text: Bardet-Biedl syndrome 3 (Bbs3) knockout mouse model reveals common BBS-associated phenotypes and Bbs3 unique phenotypes.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:8821035
  review:
    summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
    action: KEEP_AS_NON_CORE
    reason: Over-general CC parent.
    supported_by:
    - reference_id: PMID:8821035
      supporting_text: Expression of catenins during mouse embryonic development and in adult tissues.
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:12885771
  review:
    summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
    action: ACCEPT
    reason: Genuine junctional pool; IDA-supported.
    supported_by:
    - reference_id: PMID:12885771
      supporting_text: beta-Catenin is required for specification of proximal/distal cell fate during lung morphogenesis.
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:14625387
  review:
    summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
    action: ACCEPT
    reason: Genuine junctional pool; IDA-supported.
    supported_by:
    - reference_id: PMID:14625387
      supporting_text: Foxj1 is required for apical localization of ezrin in airway epithelial cells.
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:15226261
  review:
    summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
    action: ACCEPT
    reason: Genuine junctional pool; IDA-supported.
    supported_by:
    - reference_id: PMID:15226261
      supporting_text: Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization.
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:17671182
  review:
    summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
    action: ACCEPT
    reason: Genuine junctional pool; IDA-supported.
    supported_by:
    - reference_id: PMID:17671182
      supporting_text: Haploinsufficiency of KrΓΌppel-like factor 4 promotes adenomatous polyposis coli dependent intestinal tumorigenesis.
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:20016102
  review:
    summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
    action: ACCEPT
    reason: Genuine junctional pool; IDA-supported.
    supported_by:
    - reference_id: PMID:20016102
      supporting_text: The small GTPase Rac1 regulates auditory hair cell morphogenesis.
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:20089884
  review:
    summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
    action: ACCEPT
    reason: Genuine junctional pool; IDA-supported.
    supported_by:
    - reference_id: PMID:20089884
      supporting_text: Milk secretion and ejection are impaired in the mammary gland of mice harboring a Cx43 mutant while expression and localization of tight and adherens junction proteins remain unchanged.
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:9950951
  review:
    summary: Beta-catenin localizes to the basolateral membrane domain of epithelia, the site of cadherin-based cell-cell contacts.
    action: ACCEPT
    reason: Genuine junctional pool; IDA-supported.
    supported_by:
    - reference_id: PMID:9950951
      supporting_text: Nuclear localization of beta-catenin and loss of apical brush border actin in cystic tubules of bcl-2 -/- mice.
- term:
    id: GO:0016327
    label: apicolateral plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:29211732
  review:
    summary: Beta-catenin concentrates at the apicolateral membrane where adherens junctions form between polarized epithelial cells.
    action: ACCEPT
    reason: Genuine junctional membrane localization; IDA.
    supported_by:
    - reference_id: PMID:29211732
      supporting_text: The mouse Jhy gene regulates ependymal cell differentiation and ciliogenesis.
- term:
    id: GO:0016328
    label: lateral plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000008
  review:
    summary: Beta-catenin concentrates at the lateral membrane of epithelia where cadherin-based cell-cell junctions assemble.
    action: ACCEPT
    reason: Genuine core junctional membrane pool; IDA.
- term:
    id: GO:0016328
    label: lateral plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:15645444
  review:
    summary: Beta-catenin concentrates at the lateral membrane of epithelia where cadherin-based cell-cell junctions assemble.
    action: ACCEPT
    reason: Genuine core junctional membrane pool; IDA.
    supported_by:
    - reference_id: PMID:15645444
      supporting_text: Gene expression profile analysis of mouse colon embryonic development.
- term:
    id: GO:0016342
    label: catenin complex
  evidence_type: IDA
  original_reference_id: PMID:8853988
  review:
    summary: Beta-catenin is a defining member of the catenin (cadherin-catenin) complex linking cadherins to alpha-catenin/actin.
    action: ACCEPT
    reason: Core complex; broadly supported (IBA/IDA/IMP/ISS).
    supported_by:
    - reference_id: PMID:8853988
      supporting_text: Expression and cell membrane localization of catenins during mouse preimplantation development.
- term:
    id: GO:0030018
    label: Z disc
  evidence_type: IDA
  original_reference_id: PMID:8821035
  review:
    summary: Beta-catenin localizes to the cardiomyocyte Z disc/intercalated-disc region, a muscle-specific adhesion structure secondary to its general adherens-junction role.
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific (muscle) localization; IDA but non-core.
    supported_by:
    - reference_id: PMID:8821035
      supporting_text: Expression of catenins during mouse embryonic development and in adult tissues.
- term:
    id: GO:0030027
    label: lamellipodium
  evidence_type: IDA
  original_reference_id: PMID:14657280
  review:
    summary: A lamellipodial pool reflects beta-catenin at dynamic actin-rich protrusions, secondary to its stable junctional localization.
    action: KEEP_AS_NON_CORE
    reason: Context-specific localization; IDA, non-core.
    supported_by:
    - reference_id: PMID:14657280
      supporting_text: 'Lamellipodium extension and cadherin adhesion: two cell responses to cadherin activation relying on distinct signalling pathways.'
- term:
    id: GO:0030877
    label: beta-catenin destruction complex
  evidence_type: IDA
  original_reference_id: PMID:10318824
  review:
    summary: In the absence of Wnt, beta-catenin is the substrate within the AXIN/APC/GSK3B/CK1 destruction complex that drives its phosphorylation and degradation.
    action: ACCEPT
    reason: Core Wnt regulation; defining complex membership (IDA/ISS).
    supported_by:
    - reference_id: PMID:10318824
      supporting_text: Functional domains of axin. Importance of the C terminus as an oligomerization domain.
- term:
    id: GO:0031253
    label: cell projection membrane
  evidence_type: IDA
  original_reference_id: PMID:16621792
  review:
    summary: Localization to cell-projection membranes (e.g. neuronal processes) is a specialized pool secondary to beta-catenin's epithelial junction role.
    action: KEEP_AS_NON_CORE
    reason: Context-specific membrane pool; IDA but peripheral.
    supported_by:
    - reference_id: PMID:16621792
      supporting_text: 'Membrane localization of adenomatous polyposis coli protein at cellular protrusions: targeting sequences and regulation by beta-catenin.'
- term:
    id: GO:0031528
    label: microvillus membrane
  evidence_type: IDA
  original_reference_id: PMID:16439479
  review:
    summary: A microvillus-membrane pool is a specialized apical localization in particular epithelia, secondary to core junctional pools.
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific localization; IDA, non-core.
    supported_by:
    - reference_id: PMID:16439479
      supporting_text: Foxf1 and Foxf2 control murine gut development by limiting mesenchymal Wnt signaling and promoting extracellular matrix production.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: ISO
  original_reference_id: PMID:22083958
  review:
    summary: Bare 'protein-containing complex' is uninformative; beta-catenin's specific complexes (catenin, TCF, destruction) are annotated separately.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic CC over-annotation.
    supported_by:
    - reference_id: PMID:22083958
      supporting_text: Histone H1 recruitment by CHD8 is essential for suppression of the Wnt-Ξ²-catenin signaling pathway.
- term:
    id: GO:0043296
    label: apical junction complex
  evidence_type: IDA
  original_reference_id: PMID:16249236
  review:
    summary: Beta-catenin is a component of the epithelial apical junction complex via the cadherin-catenin adhesion system.
    action: ACCEPT
    reason: Core epithelial junction localization; IDA.
    supported_by:
    - reference_id: PMID:16249236
      supporting_text: Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network.
- term:
    id: GO:0043296
    label: apical junction complex
  evidence_type: IDA
  original_reference_id: PMID:17130295
  review:
    summary: Beta-catenin is a component of the epithelial apical junction complex via the cadherin-catenin adhesion system.
    action: ACCEPT
    reason: Core epithelial junction localization; IDA.
    supported_by:
    - reference_id: PMID:17130295
      supporting_text: Distinct subdomain organization and molecular composition of a tight junction with adherens junction features.
- term:
    id: GO:0043296
    label: apical junction complex
  evidence_type: IDA
  original_reference_id: PMID:17666436
  review:
    summary: Beta-catenin is a component of the epithelial apical junction complex via the cadherin-catenin adhesion system.
    action: ACCEPT
    reason: Core epithelial junction localization; IDA.
    supported_by:
    - reference_id: PMID:17666436
      supporting_text: Shroom2, a myosin-VIIa- and actin-binding protein, directly interacts with ZO-1 at tight junctions.
- term:
    id: GO:0045177
    label: apical part of cell
  evidence_type: IDA
  original_reference_id: PMID:14758363
  review:
    summary: Beta-catenin localizes apically in polarized epithelia where adherens junctions concentrate near the apical pole.
    action: ACCEPT
    reason: Genuine epithelial pool; IDA-supported.
    supported_by:
    - reference_id: PMID:14758363
      supporting_text: The hyh mutation uncovers roles for alpha Snap in apical protein localization and control of neural cell fate.
- term:
    id: GO:0045177
    label: apical part of cell
  evidence_type: IDA
  original_reference_id: PMID:15037549
  review:
    summary: Beta-catenin localizes apically in polarized epithelia where adherens junctions concentrate near the apical pole.
    action: ACCEPT
    reason: Genuine epithelial pool; IDA-supported.
    supported_by:
    - reference_id: PMID:15037549
      supporting_text: Loss of cell polarity causes severe brain dysplasia in Lgl1 knockout mice.
- term:
    id: GO:0045177
    label: apical part of cell
  evidence_type: IDA
  original_reference_id: PMID:16249236
  review:
    summary: Beta-catenin localizes apically in polarized epithelia where adherens junctions concentrate near the apical pole.
    action: ACCEPT
    reason: Genuine epithelial pool; IDA-supported.
    supported_by:
    - reference_id: PMID:16249236
      supporting_text: Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network.
- term:
    id: GO:0045177
    label: apical part of cell
  evidence_type: IDA
  original_reference_id: PMID:23863479
  review:
    summary: Beta-catenin localizes apically in polarized epithelia where adherens junctions concentrate near the apical pole.
    action: ACCEPT
    reason: Genuine epithelial pool; IDA-supported.
    supported_by:
    - reference_id: PMID:23863479
      supporting_text: Tumor suppressor Nf2 limits expansion of the neural progenitor pool by inhibiting Yap/Taz transcriptional coactivators.
- term:
    id: GO:0045294
    label: alpha-catenin binding
  evidence_type: IDA
  original_reference_id: PMID:12432063
  review:
    summary: Beta-catenin binds alpha-catenin via its N-terminal region, the key linkage coupling the cadherin-catenin complex to the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural MF; crystallographically defined, IPI/IDA.
    supported_by:
    - reference_id: PMID:12432063
      supporting_text: Protein kinase CKII regulates the interaction of beta-catenin with alpha-catenin and its protein stability.
- term:
    id: GO:0045296
    label: cadherin binding
  evidence_type: ISO
  original_reference_id: PMID:10330403
  review:
    summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
    action: ACCEPT
    reason: Core structural MF; crystallographically defined, IPI/IBA.
    supported_by:
    - reference_id: PMID:10330403
      supporting_text: Domains of axin involved in protein-protein interactions, Wnt pathway inhibition, and intracellular localization.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0045296
    label: cadherin binding
  evidence_type: IPI
  original_reference_id: PMID:15023525
  review:
    summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
    action: ACCEPT
    reason: Core structural MF; crystallographically defined, IPI/IBA.
    supported_by:
    - reference_id: PMID:15023525
      supporting_text: Ksp-cadherin is a functional cell-cell adhesion molecule related to LI-cadherin.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0045296
    label: cadherin binding
  evidence_type: IPI
  original_reference_id: PMID:15057752
  review:
    summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
    action: ACCEPT
    reason: Core structural MF; crystallographically defined, IPI/IBA.
    supported_by:
    - reference_id: PMID:15057752
      supporting_text: Beta-catenin is temporally regulated during normal liver development.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0045296
    label: cadherin binding
  evidence_type: IPI
  original_reference_id: PMID:8853988
  review:
    summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
    action: ACCEPT
    reason: Core structural MF; crystallographically defined, IPI/IBA.
    supported_by:
    - reference_id: PMID:8853988
      supporting_text: Expression and cell membrane localization of catenins during mouse preimplantation development.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0061629
    label: RNA polymerase II-specific DNA-binding transcription factor binding
  evidence_type: IDA
  original_reference_id: PMID:16678101
  review:
    summary: Beta-catenin directly binds Pol II-specific DNA-binding transcription factors (TCF/LEF) to drive Wnt-responsive transcription.
    action: ACCEPT
    reason: Core Wnt coactivation; IDA-supported specific TF binding.
    supported_by:
    - reference_id: PMID:16678101
      supporting_text: Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
- term:
    id: GO:0061629
    label: RNA polymerase II-specific DNA-binding transcription factor binding
  evidence_type: IDA
  original_reference_id: PMID:22665494
  review:
    summary: Beta-catenin directly binds Pol II-specific DNA-binding transcription factors (TCF/LEF) to drive Wnt-responsive transcription.
    action: ACCEPT
    reason: Core Wnt coactivation; IDA-supported specific TF binding.
    supported_by:
    - reference_id: PMID:22665494
      supporting_text: mrhl RNA, a long noncoding RNA, negatively regulates Wnt signaling through its protein partner Ddx5/p68 in mouse spermatogonial cells.
- term:
    id: GO:0140677
    label: molecular function activator activity
  evidence_type: EXP
  original_reference_id: PMID:21075118
  review:
    summary: Beta-catenin's nuclear role is to act as a transcriptional coactivator (activator) for TCF/LEF factors; this captures its direct molecular-activator function in the Wnt output.
    action: ACCEPT
    reason: "Direct: as a TCF/LEF coactivator it activates a partner's molecular function, a genuine core MF of beta-catenin."
    supported_by:
    - reference_id: PMID:21075118
      supporting_text: Biochemical and structural characterization of Ξ²-catenin interactions with nonphosphorylated and CK2-phosphorylated Lef-1.
- term:
    id: GO:0021854
    label: hypothalamus development
  evidence_type: IMP
  original_reference_id: PMID:32868762
  review:
    summary: Beta-catenin supports hypothalamic neuronal specification via Wnt-driven transcription; a CNS developmental outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven hypothalamus development
    supported_by:
    - reference_id: PMID:32868762
      supporting_text: The cellular and molecular landscape of hypothalamic patterning and differentiation from embryonic to late postnatal development.
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:32868762
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:32868762
      supporting_text: The cellular and molecular landscape of hypothalamic patterning and differentiation from embryonic to late postnatal development.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9773219
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9860515
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9860560
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9860569
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9863577
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-9761463
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:30389919
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:30389919
      supporting_text: ARTS mediates apoptosis and regeneration of the intestinal stem cell niche.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:30389919
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:30389919
      supporting_text: ARTS mediates apoptosis and regeneration of the intestinal stem cell niche.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9735211
  review:
    summary: Stabilized beta-catenin accumulates in the nucleoplasm to act as the Wnt transcriptional coactivator.
    action: ACCEPT
    reason: Genuine nuclear pool; TAS.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9754284
  review:
    summary: Stabilized beta-catenin accumulates in the nucleoplasm to act as the Wnt transcriptional coactivator.
    action: ACCEPT
    reason: Genuine nuclear pool; TAS.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9793864
  review:
    summary: Stabilized beta-catenin accumulates in the nucleoplasm to act as the Wnt transcriptional coactivator.
    action: ACCEPT
    reason: Genuine nuclear pool; TAS.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9794042
  review:
    summary: Stabilized beta-catenin accumulates in the nucleoplasm to act as the Wnt transcriptional coactivator.
    action: ACCEPT
    reason: Genuine nuclear pool; TAS.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9823738
  review:
    summary: Stabilized beta-catenin accumulates in the nucleoplasm to act as the Wnt transcriptional coactivator.
    action: ACCEPT
    reason: Genuine nuclear pool; TAS.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9824206
  review:
    summary: Stabilized beta-catenin accumulates in the nucleoplasm to act as the Wnt transcriptional coactivator.
    action: ACCEPT
    reason: Genuine nuclear pool; TAS.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9824277
  review:
    summary: Stabilized beta-catenin accumulates in the nucleoplasm to act as the Wnt transcriptional coactivator.
    action: ACCEPT
    reason: Genuine nuclear pool; TAS.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9824278
  review:
    summary: Stabilized beta-catenin accumulates in the nucleoplasm to act as the Wnt transcriptional coactivator.
    action: ACCEPT
    reason: Genuine nuclear pool; TAS.
- term:
    id: GO:0140297
    label: DNA-binding transcription factor binding
  evidence_type: IPI
  original_reference_id: PMID:22723415
  review:
    summary: Beta-catenin binds TCF/LEF DNA-binding transcription factors to coactivate Wnt target genes; core to its nuclear Wnt-effector role.
    action: ACCEPT
    reason: 'Core Wnt: direct TCF/LEF coactivation (IPI); foundational MF for the transcriptional arm.'
    supported_by:
    - reference_id: PMID:22723415
      supporting_text: Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:20399730
  review:
    summary: Beta-catenin is a defining structural component of the adherens junction, bridging E-cadherin to alpha-catenin and the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural localization; strongly supported (IBA/IDA).
    supported_by:
    - reference_id: PMID:20399730
      supporting_text: The apical complex couples cell fate and cell survival to cerebral cortical development.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:17920587
  review:
    summary: The majority of beta-catenin is at the plasma membrane within cadherin-catenin junctional complexes.
    action: ACCEPT
    reason: Core localization; IDA/TAS-supported.
    supported_by:
    - reference_id: PMID:17920587
      supporting_text: FERM protein EPB41L5 is a novel member of the mammalian CRB-MPP5 polarity complex.
- term:
    id: GO:1990907
    label: beta-catenin-TCF complex
  evidence_type: IDA
  original_reference_id: PMID:20371816
  review:
    summary: The nuclear beta-catenin-TCF complex is the central transcriptional effector unit of canonical Wnt signaling.
    action: ACCEPT
    reason: Core Wnt effector complex; IDA-supported.
    supported_by:
    - reference_id: PMID:20371816
      supporting_text: LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1g) in thalamic neurons of the adult brain.
- term:
    id: GO:0032968
    label: positive regulation of transcription elongation by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:30478225
  review:
    summary: IMP annotation; beta-catenin can promote elongation (e.g. via TNIK/PAF1c at Wnt targets), a specific mechanistic facet that is secondary to its core coactivator recruitment role.
    action: KEEP_AS_NON_CORE
    reason: Specific mechanistic facet; experimental, downgrade not remove.
    supported_by:
    - reference_id: PMID:30478225
      supporting_text: TBX2 and TBX3 act downstream of canonical WNT signaling in patterning and differentiation of the mouse ureteric mesenchyme.
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:30478225
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:30478225
      supporting_text: TBX2 and TBX3 act downstream of canonical WNT signaling in patterning and differentiation of the mouse ureteric mesenchyme.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15110721
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:15110721
      supporting_text: Sox1 acts through multiple independent pathways to promote neurogenesis.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:15110721
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
    supported_by:
    - reference_id: PMID:15110721
      supporting_text: Sox1 acts through multiple independent pathways to promote neurogenesis.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31073040
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:31073040
      supporting_text: LMBR1L regulates lymphopoiesis through Wnt/Ξ²-catenin signaling.
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: IDA
  original_reference_id: PMID:24338362
  review:
    summary: Beta-catenin localizes to cell-cell junctions (adherens junctions) as a structural complex component.
    action: ACCEPT
    reason: Core junctional localization; IDA.
    supported_by:
    - reference_id: PMID:24338362
      supporting_text: POPX2 phosphatase regulates the KIF3 kinesin motor complex.
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:15314168
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:15314168
      supporting_text: Cyclin D1 genetic heterozygosity regulates colonic epithelial cell differentiation and tumor number in ApcMin mice.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: IMP
  original_reference_id: PMID:26371318
  review:
    summary: 'The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.'
    action: ACCEPT
    reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
    supported_by:
    - reference_id: PMID:26371318
      supporting_text: Lhx2 regulates the timing of Ξ²-catenin-dependent cortical neurogenesis.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IMP
  original_reference_id: PMID:26371318
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:26371318
      supporting_text: Lhx2 regulates the timing of Ξ²-catenin-dependent cortical neurogenesis.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:26371318
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
    supported_by:
    - reference_id: PMID:26371318
      supporting_text: Lhx2 regulates the timing of Ξ²-catenin-dependent cortical neurogenesis.
- term:
    id: GO:0050768
    label: negative regulation of neurogenesis
  evidence_type: IMP
  original_reference_id: PMID:26371318
  review:
    summary: Beta-catenin can suppress neuronal differentiation by maintaining neural progenitors (Wnt stemness targets); a downstream CNS-development phenotype.
    action: KEEP_AS_NON_CORE
    reason: Neurogenesis suppression downstream of Wnt progenitor-maintenance transcription.
    supported_by:
    - reference_id: PMID:26371318
      supporting_text: Lhx2 regulates the timing of Ξ²-catenin-dependent cortical neurogenesis.
- term:
    id: GO:2000179
    label: positive regulation of neural precursor cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:26371318
  review:
    summary: Beta-catenin enlarges the neural precursor pool by activating Wnt cell-cycle genes; a downstream CNS-development phenotype.
    action: KEEP_AS_NON_CORE
    reason: Neural-precursor expansion downstream of Wnt mitogenic targets.
    supported_by:
    - reference_id: PMID:26371318
      supporting_text: Lhx2 regulates the timing of Ξ²-catenin-dependent cortical neurogenesis.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:20371816
  review:
    summary: In the nucleus beta-catenin associates with chromatin at Wnt target genes as part of TCF/LEF transcription complexes.
    action: ACCEPT
    reason: Core nuclear Wnt role; IDA/IGI-supported.
    supported_by:
    - reference_id: PMID:20371816
      supporting_text: LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1g) in thalamic neurons of the adult brain.
- term:
    id: GO:1990907
    label: beta-catenin-TCF complex
  evidence_type: IDA
  original_reference_id: PMID:9488439
  review:
    summary: The nuclear beta-catenin-TCF complex is the central transcriptional effector unit of canonical Wnt signaling.
    action: ACCEPT
    reason: Core Wnt effector complex; IDA-supported.
    supported_by:
    - reference_id: PMID:9488439
      supporting_text: Two members of the Tcf family implicated in Wnt/beta-catenin signaling during embryogenesis in the mouse.
- term:
    id: GO:1990138
    label: neuron projection extension
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Ortholog/electronic-inferred role in axon/dendrite outgrowth, plausibly via cadherin-junction and Wnt-transcriptional inputs; a downstream neuronal phenotype.
    action: KEEP_AS_NON_CORE
    reason: Neurite extension downstream of adhesion/Wnt roles; non-core (electronic).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25232112
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:25232112
      supporting_text: Dlg5 regulates dendritic spine formation and synaptogenesis by controlling subcellular N-cadherin localization.
- term:
    id: GO:0045202
    label: synapse
  evidence_type: IDA
  original_reference_id: PMID:25232112
  review:
    summary: Synaptic localization supports cadherin-based synaptic adhesion in neurons, a tissue-specific pool.
    action: KEEP_AS_NON_CORE
    reason: Synapse localization; IDA/IEA, non-core.
    supported_by:
    - reference_id: PMID:25232112
      supporting_text: Dlg5 regulates dendritic spine formation and synaptogenesis by controlling subcellular N-cadherin localization.
- term:
    id: GO:0016525
    label: negative regulation of angiogenesis
  evidence_type: IMP
  original_reference_id: PMID:25961718
  review:
    summary: Endothelial Wnt/beta-catenin signaling can restrain vessel sprouting through transcriptional targets; a context-dependent downstream vascular phenotype.
    action: KEEP_AS_NON_CORE
    reason: Angiogenesis regulation downstream of endothelial Wnt-transcriptional output.
    supported_by:
    - reference_id: PMID:25961718
      supporting_text: Resveratrol-Induced Vascular Progenitor Differentiation towards Endothelial Lineage via MiR-21/Akt/Ξ²-Catenin Is Protective in Vessel Graft Models.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:24681597
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:24681597
      supporting_text: Kindlin-1 controls Wnt and TGF-Ξ² availability to regulate cutaneous stem cell proliferation.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:24681597
  review:
    summary: Beta-catenin maintains a genuine cytoplasmic pool, where it is held in the destruction complex or bound to cadherin tails before junction delivery.
    action: ACCEPT
    reason: Genuine pool; strongly supported (IDA/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:24681597
      supporting_text: Kindlin-1 controls Wnt and TGF-Ξ² availability to regulate cutaneous stem cell proliferation.
- term:
    id: GO:0051884
    label: regulation of timing of anagen
  evidence_type: IDA
  original_reference_id: PMID:24681597
  review:
    summary: Beta-catenin Wnt activity initiates the hair-follicle growth (anagen) phase; an IDA developmental-timing phenotype downstream of transcription.
    action: KEEP_AS_NON_CORE
    reason: Hair-cycle anagen timing downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:24681597
      supporting_text: Kindlin-1 controls Wnt and TGF-Ξ² availability to regulate cutaneous stem cell proliferation.
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:24681597
  review:
    summary: 'The definitional core function: beta-catenin is the key downstream effector of the canonical Wnt pathway, stabilized upon Wnt to drive TCF/LEF target genes. Broadly supported (IDA/IMP/IGI).'
    action: ACCEPT
    reason: Central, multiply-supported core function of the gene.
    supported_by:
    - reference_id: PMID:24681597
      supporting_text: Kindlin-1 controls Wnt and TGF-Ξ² availability to regulate cutaneous stem cell proliferation.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0016342
    label: catenin complex
  evidence_type: IMP
  original_reference_id: PMID:11121423
  review:
    summary: Beta-catenin is a defining member of the catenin (cadherin-catenin) complex linking cadherins to alpha-catenin/actin.
    action: ACCEPT
    reason: Core complex; broadly supported (IBA/IDA/IMP/ISS).
    supported_by:
    - reference_id: PMID:11121423
      supporting_text: The cadherin cytoplasmic domain is unstructured in the absence of beta-catenin. A possible mechanism for regulating cadherin turnover.
- term:
    id: GO:0045296
    label: cadherin binding
  evidence_type: IPI
  original_reference_id: PMID:11121423
  review:
    summary: Beta-catenin binds the cytoplasmic tail of classical cadherins (E-/N-cadherin) via its armadillo repeats, the founding interaction of the cadherin-catenin complex.
    action: ACCEPT
    reason: Core structural MF; crystallographically defined, IPI/IBA.
    supported_by:
    - reference_id: PMID:11121423
      supporting_text: The cadherin cytoplasmic domain is unstructured in the absence of beta-catenin. A possible mechanism for regulating cadherin turnover.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0097718
    label: disordered domain specific binding
  evidence_type: IPI
  original_reference_id: PMID:11121423
  review:
    summary: Binding to intrinsically disordered regions of partners (e.g. cadherin/APC tails) is a real biophysical mode but a generic descriptor of specific interactions captured elsewhere.
    action: KEEP_AS_NON_CORE
    reason: Generic-ish MF; IPI but peripheral to named partner terms.
    supported_by:
    - reference_id: PMID:11121423
      supporting_text: The cadherin cytoplasmic domain is unstructured in the absence of beta-catenin. A possible mechanism for regulating cadherin turnover.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:20371816
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:20371816
      supporting_text: LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1g) in thalamic neurons of the adult brain.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:20371816
  review:
    summary: Beta-catenin has a cytosolic pool subject to destruction-complex regulation and Wnt-dependent stabilization.
    action: ACCEPT
    reason: Genuine pool; IDA/TAS-supported.
    supported_by:
    - reference_id: PMID:20371816
      supporting_text: LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1g) in thalamic neurons of the adult brain.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:20371816
  review:
    summary: Bare 'membrane' is uninformative given the specific plasma-membrane/junction terms already capturing beta-catenin's localization.
    action: KEEP_AS_NON_CORE
    reason: Over-general CC parent.
    supported_by:
    - reference_id: PMID:20371816
      supporting_text: LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1g) in thalamic neurons of the adult brain.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IGI
  original_reference_id: PMID:20371816
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
    supported_by:
    - reference_id: PMID:20371816
      supporting_text: LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1g) in thalamic neurons of the adult brain.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:25979161
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:25979161
      supporting_text: Transmembrane protein 64 reciprocally regulates osteoblast and adipocyte differentiation by modulating Wnt/Ξ²-catenin signaling.
- term:
    id: GO:1904948
    label: midbrain dopaminergic neuron differentiation
  evidence_type: IMP
  original_reference_id: PMID:19122665
  review:
    summary: Beta-catenin drives midbrain dopaminergic neuron differentiation via Wnt1/TCF transcription; a neuronal cell-fate outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven midbrain DA neuron fate
    supported_by:
    - reference_id: PMID:19122665
      supporting_text: Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:22645310
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:22645310
      supporting_text: Prolyl isomerase Pin1 regulates neuronal differentiation via Ξ²-catenin.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:22645310
  review:
    summary: Beta-catenin has a cytosolic pool subject to destruction-complex regulation and Wnt-dependent stabilization.
    action: ACCEPT
    reason: Genuine pool; IDA/TAS-supported.
    supported_by:
    - reference_id: PMID:22645310
      supporting_text: Prolyl isomerase Pin1 regulates neuronal differentiation via Ξ²-catenin.
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: IPI
  original_reference_id: PMID:22645310
  review:
    summary: Bare 'enzyme binding' is uninformative; beta-catenin's relevant enzyme contacts (GSK3B, CK1, kinases) are captured by specific kinase/phosphatase terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:22645310
      supporting_text: Prolyl isomerase Pin1 regulates neuronal differentiation via Ξ²-catenin.
- term:
    id: GO:1904888
    label: cranial skeletal system development
  evidence_type: IMP
  original_reference_id: PMID:11262227
  review:
    summary: Beta-catenin patterns craniofacial skeleton via Wnt-driven osteochondral fate decisions; a skeletal developmental outcome, not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven craniofacial skeletogenesis
    supported_by:
    - reference_id: PMID:11262227
      supporting_text: Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
- term:
    id: GO:0030901
    label: midbrain development
  evidence_type: IMP
  original_reference_id: PMID:11262227
  review:
    summary: Beta-catenin patterns midbrain via Wnt/TCF transcription and progenitor control; a CNS developmental outcome, not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven midbrain development
    supported_by:
    - reference_id: PMID:11262227
      supporting_text: Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
- term:
    id: GO:0030902
    label: hindbrain development
  evidence_type: IMP
  original_reference_id: PMID:11262227
  review:
    summary: Beta-catenin patterns hindbrain via Wnt/TCF transcription and progenitor control; a CNS developmental outcome, not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven hindbrain development
    supported_by:
    - reference_id: PMID:11262227
      supporting_text: Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
- term:
    id: GO:0061550
    label: cranial ganglion development
  evidence_type: IMP
  original_reference_id: PMID:11262227
  review:
    summary: Beta-catenin supports cranial ganglion/placode development through Wnt/TCF transcription; a neural-crest/placode outcome downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt role in cranial ganglion development
    supported_by:
    - reference_id: PMID:11262227
      supporting_text: Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
- term:
    id: GO:1990403
    label: embryonic brain development
  evidence_type: IMP
  original_reference_id: PMID:11262227
  review:
    summary: Beta-catenin supports embryonic brain growth/patterning via Wnt/TCF neural transcription; a CNS developmental outcome, not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven embryonic brain development
    supported_by:
    - reference_id: PMID:11262227
      supporting_text: Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
- term:
    id: GO:1990791
    label: dorsal root ganglion development
  evidence_type: IMP
  original_reference_id: PMID:11262227
  review:
    summary: Beta-catenin supports DRG formation from neural crest via Wnt/TCF transcription; a peripheral-nervous-system developmental outcome, not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven DRG development
    supported_by:
    - reference_id: PMID:11262227
      supporting_text: Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
- term:
    id: GO:1990909
    label: Wnt signalosome
  evidence_type: IDA
  original_reference_id: PMID:22899650
  review:
    summary: 'IDA-supported: stabilized beta-catenin is a component of the Wnt signalosome where it escapes destruction-complex phosphorylation. Core to its Wnt-effector role.'
    action: ACCEPT
    reason: Experimental component annotation central to canonical Wnt signaling.
    supported_by:
    - reference_id: PMID:22899650
      supporting_text: LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6.
- term:
    id: GO:0019901
    label: protein kinase binding
  evidence_type: IPI
  original_reference_id: PMID:22899650
  review:
    summary: Protein-kinase binding reflects regulatory contacts (GSK3B, CK1, CDKs) governing beta-catenin stability; specific destruction-complex terms are more informative.
    action: KEEP_AS_NON_CORE
    reason: Semi-generic regulatory MF; IPI, non-core.
    supported_by:
    - reference_id: PMID:22899650
      supporting_text: LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15908431
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:15908431
      supporting_text: MAGI1 recruits Dll1 to cadherin-based adherens junctions and stabilizes it on the cell surface.
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:19122665
  review:
    summary: Generic negative-regulation-of-expression parent; beta-catenin's specific repressive effects act at the level of Pol II transcription of particular targets.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative broad parent; specific Pol II transcription terms preferred.
    supported_by:
    - reference_id: PMID:19122665
      supporting_text: Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis.
- term:
    id: GO:0030182
    label: neuron differentiation
  evidence_type: IMP
  original_reference_id: PMID:25009587
  review:
    summary: Beta-catenin influences neuronal differentiation timing via Wnt-target transcription; a downstream neurodevelopmental process.
    action: KEEP_AS_NON_CORE
    reason: Neuronal differentiation downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:25009587
      supporting_text: Depletion of canonical Wnt signaling components has a neuroprotective effect on midbrain dopaminergic neurons in an MPTP-induced mouse model of Parkinson's disease.
- term:
    id: GO:0016600
    label: flotillin complex
  evidence_type: IDA
  original_reference_id: PMID:24046456
  review:
    summary: A reported flotillin-complex association reflects a membrane microdomain pool, peripheral to beta-catenin's core junction/Wnt functions.
    action: KEEP_AS_NON_CORE
    reason: Specialized complex; IDA but non-core.
    supported_by:
    - reference_id: PMID:24046456
      supporting_text: Flotillin microdomains stabilize cadherins at cell-cell junctions.
- term:
    id: GO:0000791
    label: euchromatin
  evidence_type: IDA
  original_reference_id: PMID:22723415
  review:
    summary: beta-catenin localizes with active TCF/LEF target loci in euchromatin, consistent with its coactivator role, but this CC term is contextual rather than a core function statement.
    action: KEEP_AS_NON_CORE
    reason: Localization term supporting, but not equal to, its coactivator function.
    supported_by:
    - reference_id: PMID:22723415
      supporting_text: Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
- term:
    id: GO:0005667
    label: transcription regulator complex
  evidence_type: IDA
  original_reference_id: PMID:22723415
  review:
    summary: Beta-catenin is a component of transcription regulator complexes (with TCF/LEF and coactivators) that drive Wnt target gene expression.
    action: ACCEPT
    reason: Core nuclear Wnt effector complex; IDA-supported.
    supported_by:
    - reference_id: PMID:22723415
      supporting_text: Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
- term:
    id: GO:0002052
    label: positive regulation of neuroblast proliferation
  evidence_type: IMP
  original_reference_id: PMID:21325504
  review:
    summary: Beta-catenin positively drives neuroblast expansion through Wnt cell-cycle targets; a downstream neurodevelopmental proliferative role.
    action: KEEP_AS_NON_CORE
    reason: Pro-neuroblast proliferation downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:21325504
      supporting_text: Frizzled3 is required for neurogenesis and target innervation during sympathetic nervous system development.
- term:
    id: GO:0045976
    label: negative regulation of mitotic cell cycle, embryonic
  evidence_type: IMP
  original_reference_id: PMID:21325504
  review:
    summary: Beta-catenin restrains embryonic mitotic cycling in specific contexts via Wnt cell-cycle target genes; a downstream developmental phenotype.
    action: KEEP_AS_NON_CORE
    reason: Embryonic cell-cycle restraint downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:21325504
      supporting_text: Frizzled3 is required for neurogenesis and target innervation during sympathetic nervous system development.
- term:
    id: GO:0061549
    label: sympathetic ganglion development
  evidence_type: IMP
  original_reference_id: PMID:21325504
  review:
    summary: Beta-catenin Wnt signaling supports sympathetic neuron lineage development; a downstream peripheral-nervous-system phenotype.
    action: KEEP_AS_NON_CORE
    reason: Sympathetic ganglion development downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:21325504
      supporting_text: Frizzled3 is required for neurogenesis and target innervation during sympathetic nervous system development.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23856522
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:23856522
      supporting_text: Jmjd3 controls mesodermal and cardiovascular differentiation of embryonic stem cells.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:23856522
  review:
    summary: Nuclear accumulation of stabilized beta-catenin is essential for its role as the canonical Wnt transcriptional effector.
    action: ACCEPT
    reason: Core localization; broadly supported (IDA/IMP/IPI). Retain, not REMOVE.
    supported_by:
    - reference_id: PMID:23856522
      supporting_text: Jmjd3 controls mesodermal and cardiovascular differentiation of embryonic stem cells.
- term:
    id: GO:0016922
    label: nuclear receptor binding
  evidence_type: IPI
  original_reference_id: PMID:14687547
  review:
    summary: Beta-catenin coactivates several nuclear receptors (e.g. NR5A2, AR/ER), broadening its transcriptional crosstalk beyond the core TCF/LEF axis.
    action: KEEP_AS_NON_CORE
    reason: Crosstalk coactivation; non-core relative to TCF.
    supported_by:
    - reference_id: PMID:14687547
      supporting_text: RORalpha coordinates reciprocal signaling in cerebellar development through sonic hedgehog and calcium-dependent pathways.
- term:
    id: GO:0033234
    label: negative regulation of protein sumoylation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Ortholog/electronic-inferred negative effect on SUMOylation; an indirect downstream activity unrelated to beta-catenin's core adhesion/Wnt functions.
    action: KEEP_AS_NON_CORE
    reason: SUMOylation suppression, electronic-inferred and indirect; non-core.
- term:
    id: GO:0048643
    label: positive regulation of skeletal muscle tissue development
  evidence_type: IMP
  original_reference_id: PMID:23460868
  review:
    summary: Beta-catenin Wnt signaling supports skeletal muscle tissue formation by driving myogenic gene programs; a downstream tissue-development role.
    action: KEEP_AS_NON_CORE
    reason: Skeletal muscle development downstream of Wnt/beta-catenin transcription.
    supported_by:
    - reference_id: PMID:23460868
      supporting_text: Ξ²-catenin is essential for efficient in vitro premyogenic mesoderm formation but can be partially compensated by retinoic acid signalling.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11590244
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:11590244
      supporting_text: 'alphaT-catenin: a novel tissue-specific beta-catenin-binding protein mediating strong cell-cell adhesion.'
- term:
    id: GO:0036023
    label: embryonic skeletal limb joint morphogenesis
  evidence_type: IGI
  original_reference_id: PMID:21262216
  review:
    summary: Beta-catenin specifies limb joint interzones via Wnt/TCF transcription (IGI); a skeletal morphogenetic outcome downstream of its signaling role.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven limb joint morphogenesis
    supported_by:
    - reference_id: PMID:21262216
      supporting_text: The zinc finger transcription factors Osr1 and Osr2 control synovial joint formation.
- term:
    id: GO:0045294
    label: alpha-catenin binding
  evidence_type: IPI
  original_reference_id: PMID:21393547
  review:
    summary: Beta-catenin binds alpha-catenin via its N-terminal region, the key linkage coupling the cadherin-catenin complex to the actin cytoskeleton.
    action: ACCEPT
    reason: Core structural MF; crystallographically defined, IPI/IDA.
    supported_by:
    - reference_id: PMID:21393547
      supporting_text: A polarized epithelium organized by beta- and alpha-catenin predates cadherin and metazoan origins.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18636119
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:18636119
      supporting_text: Coxsackievirus and adenovirus receptor (CAR) mediates atrioventricular-node function and connexin 45 localization in the murine heart.
- term:
    id: GO:0072182
    label: regulation of nephron tubule epithelial cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:19112489
  review:
    summary: Beta-catenin tunes nephron epithelial cell fate during kidney development via Wnt targets; a downstream renal phenotype.
    action: KEEP_AS_NON_CORE
    reason: Nephron epithelial differentiation control downstream of Wnt transcription.
    supported_by:
    - reference_id: PMID:19112489
      supporting_text: Gata3 acts downstream of beta-catenin signaling to prevent ectopic metanephric kidney induction.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IMP
  original_reference_id: PMID:19112489
  review:
    summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
    action: MODIFY
    reason: Generic parent; specialize to Pol II-specific positive regulation.
    proposed_replacement_terms: *id002
    supported_by:
    - reference_id: PMID:19112489
      supporting_text: Gata3 acts downstream of beta-catenin signaling to prevent ectopic metanephric kidney induction.
- term:
    id: GO:0071944
    label: cell periphery
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Beta-catenin localizes to the cell periphery at adherens junctions linking cadherins to actin; a broad location term consistent with its structural role but less specific than the junction terms.
    action: KEEP_AS_NON_CORE
    reason: electronic broad location subsumed by adherens-junction terms
- term:
    id: GO:0005938
    label: cell cortex
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Beta-catenin associates with the actin-rich cell cortex via the cadherin-catenin complex at cell-cell contacts.
    action: ACCEPT
    reason: Genuine cortical pool at junctions.
- term:
    id: GO:0007155
    label: cell adhesion
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Generic cell adhesion is subsumed by the more specific cadherin-mediated cell-cell adhesion terms that capture beta-catenin's actual mechanism.
    action: KEEP_AS_NON_CORE
    reason: Over-general parent; electronic; specific child preferred.
- term:
    id: GO:0008285
    label: negative regulation of cell population proliferation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Electronic/ortholog-inferred anti-proliferative effect in some lineages, downstream of context-specific Wnt transcriptional output.
    action: KEEP_AS_NON_CORE
    reason: Context anti-proliferation downstream of transcription; non-core (electronic).
- term:
    id: GO:0010909
    label: positive regulation of heparan sulfate proteoglycan biosynthetic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Ortholog/electronic-inferred up-regulation of HSPG biosynthesis, plausibly via Wnt transcriptional targets; a downstream biosynthetic effect.
    action: KEEP_AS_NON_CORE
    reason: HSPG biosynthesis upregulation downstream of transcription; non-core (electronic).
- term:
    id: GO:0016342
    label: catenin complex
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Beta-catenin is a defining member of the catenin (cadherin-catenin) complex linking cadherins to alpha-catenin/actin.
    action: ACCEPT
    reason: Core complex; broadly supported (IBA/IDA/IMP/ISS).
- term:
    id: GO:0030054
    label: cell junction
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Beta-catenin is a core cell-junction protein, concentrated at cadherin-based cell-cell junctions.
    action: ACCEPT
    reason: Core localization (junction parent).
- term:
    id: GO:0030877
    label: beta-catenin destruction complex
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: In the absence of Wnt, beta-catenin is the substrate within the AXIN/APC/GSK3B/CK1 destruction complex that drives its phosphorylation and degradation.
    action: ACCEPT
    reason: Core Wnt regulation; defining complex membership (IDA/ISS).
- term:
    id: GO:0030997
    label: regulation of centriole-centriole cohesion
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Beta-catenin has a reported centrosomal moonlighting role in centriole cohesion; ortholog/electronic-inferred and distinct from its core adhesion/Wnt roles.
    action: KEEP_AS_NON_CORE
    reason: Centrosomal moonlighting role, electronic-inferred; non-core.
- term:
    id: GO:0032355
    label: response to estradiol
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Ortholog/electronic-inferred responsiveness to estradiol, reflecting hormone crosstalk with Wnt/beta-catenin transcription in reproductive tissues; a downstream response.
    action: KEEP_AS_NON_CORE
    reason: Estradiol response downstream/crosstalk with Wnt transcription; non-core (electronic).
- term:
    id: GO:0032993
    label: protein-DNA complex
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Beta-catenin is part of protein-DNA complexes only indirectly via TCF/LEF; the specific beta-catenin-TCF complex terms capture this better.
    action: KEEP_AS_NON_CORE
    reason: Indirect/over-general; electronic.
- term:
    id: GO:0034333
    label: adherens junction assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: By linking cadherin to the catenin/actin machinery, beta-catenin is required for adherens junction assembly.
    action: ACCEPT
    reason: Core adhesion process; mechanistically central even if evidence is electronic/ISS.
- term:
    id: GO:0034394
    label: protein localization to cell surface
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Beta-catenin promotes surface delivery/retention of cadherin (e.g. via vinculin), a supporting trafficking role secondary to its structural function.
    action: KEEP_AS_NON_CORE
    reason: Peripheral process; electronic.
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: In some contexts beta-catenin promotes apoptosis; this electronic/ortholog-inferred bidirectional effect is a downstream consequence of context-specific transcription.
    action: KEEP_AS_NON_CORE
    reason: Context-dependent pro-apoptotic output downstream of transcription; non-core (electronic).
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'Core function: nuclear beta-catenin is the TCF/LEF coactivator that activates Wnt-responsive Pol II target genes (recruits EP300/CREBBP, BCL9). Broadly supported.'
    action: ACCEPT
    reason: Central coactivator function, multiply and experimentally supported.
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: A perinuclear cytoplasmic pool may reflect shuttling/staging intermediates, secondary to functional junctional and nuclear pools.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization; electronic.
- term:
    id: GO:0048660
    label: regulation of smooth muscle cell proliferation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Modulation of vascular/visceral smooth muscle proliferation reflects Wnt/beta-catenin mitogenic target genes; ortholog/electronic-inferred downstream process.
    action: KEEP_AS_NON_CORE
    reason: Downstream proliferative control via Wnt transcriptional targets; non-core.
- term:
    id: GO:0061154
    label: endothelial tube morphogenesis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Beta-catenin supports endothelial tube formation via junctional integrity and Wnt transcription; a vascular morphogenetic outcome (electronic) downstream of its dual role.
    action: KEEP_AS_NON_CORE
    reason: electronic; downstream of junction/Wnt vascular roles
- term:
    id: GO:0070369
    label: beta-catenin-TCF7L2 complex
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Beta-catenin forms the specific transcriptional complex with TCF7L2/TCF4 that activates Wnt target genes.
    action: ACCEPT
    reason: Core Wnt effector complex (specific TCF member).
- term:
    id: GO:0071363
    label: cellular response to growth factor stimulus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Beta-catenin participates in growth-factor-responsive transcription via Wnt crosstalk; a broad, electronically inferred response, kept as non-core given indirect linkage.
    action: KEEP_AS_NON_CORE
    reason: electronic/generic; indirect crosstalk, not core
- term:
    id: GO:0071681
    label: cellular response to indole-3-methanol
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: No credible biological basis for beta-catenin as a responder to indole-3-methanol; an electronically propagated (IEA/ISO/ISS) annotation with no support.
    action: REMOVE
    reason: electronic annotation biologically unsupported for this gene
- term:
    id: GO:0090279
    label: regulation of calcium ion import
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Ortholog/electronic-inferred influence on calcium import, distinct from beta-catenin's core Wnt/adhesion roles; a downstream/indirect effect.
    action: KEEP_AS_NON_CORE
    reason: Calcium-import regulation, electronic-inferred and indirect; non-core.
- term:
    id: GO:2000008
    label: regulation of protein localization to cell surface
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Beta-catenin modulates cadherin surface levels, a regulatory trafficking role secondary to its structural junction function.
    action: KEEP_AS_NON_CORE
    reason: Peripheral regulatory process; electronic.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20802155
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:20802155
      supporting_text: Sox17 modulates Wnt3A/beta-catenin-mediated transcriptional activation of the Lef-1 promoter.
- term:
    id: GO:0034750
    label: Scrib-APC-beta-catenin complex
  evidence_type: IDA
  original_reference_id: PMID:16611247
  review:
    summary: Beta-catenin participates in a Scrib-APC complex linked to synaptic vesicle localization and polarity, a specialized assembly beyond core adhesion/Wnt complexes.
    action: KEEP_AS_NON_CORE
    reason: Specialized complex (IDA); peripheral, neuronal-polarity context.
    supported_by:
    - reference_id: PMID:16611247
      supporting_text: Human scribble, a novel tumor suppressor identified as a target of high-risk HPV E6 for ubiquitin-mediated degradation, interacts with adenomatous polyposis coli.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IDA
  original_reference_id: PMID:20300119
  review:
    summary: Beta-catenin has a reported centrosomal pool acting in centrosome cohesion/separation, distinct from its core adhesion and Wnt roles.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization; IDA but non-core moonlighting.
    supported_by:
    - reference_id: PMID:20300119
      supporting_text: Conductin/axin2 and Wnt signalling regulates centrosome cohesion.
- term:
    id: GO:0070602
    label: regulation of centromeric sister chromatid cohesion
  evidence_type: IMP
  original_reference_id: PMID:20300119
  review:
    summary: A reported beta-catenin role at centromeric cohesion is a moonlighting function separate from its Wnt/adhesion core; supported by IMP plus electronic inference.
    action: KEEP_AS_NON_CORE
    reason: Sister-chromatid cohesion moonlighting role; non-core to Wnt/adhesion.
    supported_by:
    - reference_id: PMID:20300119
      supporting_text: Conductin/axin2 and Wnt signalling regulates centrosome cohesion.
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: IDA
  original_reference_id: PMID:12949260
  review:
    summary: 'The core molecular function: nuclear beta-catenin acts as a transcription coactivator for TCF/LEF factors, bridging EP300/CREBBP and BCL9 to Wnt target promoters. Experimentally supported.'
    action: ACCEPT
    reason: Defining molecular-function of beta-catenin; well supported (IDA/IMP).
    supported_by:
    - reference_id: PMID:12949260
      supporting_text: Wnt4 overexpression disrupts normal testicular vasculature and inhibits testosterone synthesis by repressing steroidogenic factor 1/beta-catenin synergy.
    - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
      supporting_text: Beta-catenin is a multifunctional protein with dual roles in cell adhesion and Wnt signaling
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:12949260
  review:
    summary: Correct in essence but uses the generic DNA-templated parent; beta-catenin specifically positively regulates RNA polymerase II transcription as the TCF/LEF coactivator.
    action: MODIFY
    reason: Generic parent; specialize to Pol II-specific positive regulation.
    proposed_replacement_terms: *id002
    supported_by:
    - reference_id: PMID:12949260
      supporting_text: Wnt4 overexpression disrupts normal testicular vasculature and inhibits testosterone synthesis by repressing steroidogenic factor 1/beta-catenin synergy.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20413591
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:20413591
      supporting_text: The TRPV4 channel contributes to intercellular junction formation in keratinocytes.
- term:
    id: GO:0003223
    label: ventricular compact myocardium morphogenesis
  evidence_type: TAS
  original_reference_id: PMID:20299672
  review:
    summary: Beta-catenin Wnt signaling contributes to compact-layer ventricular wall formation; a TAS downstream cardiac-morphogenesis phenotype.
    action: KEEP_AS_NON_CORE
    reason: Compact myocardium morphogenesis downstream of Wnt transcription (TAS).
    supported_by:
    - reference_id: PMID:20299672
      supporting_text: Epicardial-myocardial signaling directing coronary vasculogenesis.
- term:
    id: GO:0010718
    label: positive regulation of epithelial to mesenchymal transition
  evidence_type: TAS
  original_reference_id: PMID:20299672
  review:
    summary: Nuclear beta-catenin drives EMT transcriptional programs (Snail/Twist targets) while loss of its junctional pool also promotes EMT; the process is downstream of both core roles.
    action: KEEP_AS_NON_CORE
    reason: EMT is a transcriptional/adhesion downstream output, not beta-catenin's direct molecular function.
    supported_by:
    - reference_id: PMID:20299672
      supporting_text: Epicardial-myocardial signaling directing coronary vasculogenesis.
- term:
    id: GO:0060038
    label: cardiac muscle cell proliferation
  evidence_type: TAS
  original_reference_id: PMID:20299672
  review:
    summary: Beta-catenin supports cardiomyocyte proliferation via Wnt/TCF transcription; a cardiac-growth outcome downstream of its signaling effector role (TAS).
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven cardiomyocyte proliferation
    supported_by:
    - reference_id: PMID:20299672
      supporting_text: Epicardial-myocardial signaling directing coronary vasculogenesis.
- term:
    id: GO:0060485
    label: mesenchyme development
  evidence_type: TAS
  original_reference_id: PMID:20299672
  review:
    summary: Beta-catenin supports mesenchymal tissue development via Wnt-driven transcription; a connective-tissue developmental outcome (TAS) downstream of signaling.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven mesenchyme development
    supported_by:
    - reference_id: PMID:20299672
      supporting_text: Epicardial-myocardial signaling directing coronary vasculogenesis.
- term:
    id: GO:0060947
    label: cardiac vascular smooth muscle cell differentiation
  evidence_type: TAS
  original_reference_id: PMID:20299672
  review:
    summary: Beta-catenin promotes cardiac vascular SMC differentiation through Wnt-driven transcription; a cardiovascular cell-fate outcome, not core function (TAS).
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven cardiac SMC fate
    supported_by:
    - reference_id: PMID:20299672
      supporting_text: Epicardial-myocardial signaling directing coronary vasculogenesis.
- term:
    id: GO:0060982
    label: coronary artery morphogenesis
  evidence_type: TAS
  original_reference_id: PMID:20299672
  review:
    summary: Beta-catenin shapes coronary artery formation via epicardial/endothelial Wnt transcription; a cardiovascular morphogenetic outcome (TAS), not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven coronary morphogenesis
    supported_by:
    - reference_id: PMID:20299672
      supporting_text: Epicardial-myocardial signaling directing coronary vasculogenesis.
- term:
    id: GO:0060983
    label: epicardium-derived cardiac vascular smooth muscle cell differentiation
  evidence_type: TAS
  original_reference_id: PMID:20299672
  review:
    summary: Beta-catenin drives epicardium-derived SMC differentiation through Wnt transcription; a cardiovascular cell-fate outcome (TAS), not core function.
    action: KEEP_AS_NON_CORE
    reason: downstream Wnt-driven epicardial SMC fate
    supported_by:
    - reference_id: PMID:20299672
      supporting_text: Epicardial-myocardial signaling directing coronary vasculogenesis.
- term:
    id: GO:0072132
    label: mesenchyme morphogenesis
  evidence_type: TAS
  original_reference_id: PMID:20299672
  review:
    summary: Beta-catenin shapes mesenchymal tissue morphogenesis via Wnt transcription and adhesion; a morphogenetic outcome (TAS) of its dual role.
    action: KEEP_AS_NON_CORE
    reason: downstream of Wnt/adhesion mesenchyme morphogenesis
    supported_by:
    - reference_id: PMID:20299672
      supporting_text: Epicardial-myocardial signaling directing coronary vasculogenesis.
- term:
    id: GO:0140297
    label: DNA-binding transcription factor binding
  evidence_type: IPI
  original_reference_id: PMID:17331723
  review:
    summary: Beta-catenin binds TCF/LEF DNA-binding transcription factors to coactivate Wnt target genes; core to its nuclear Wnt-effector role.
    action: ACCEPT
    reason: 'Core Wnt: direct TCF/LEF coactivation (IPI); foundational MF for the transcriptional arm.'
    supported_by:
    - reference_id: PMID:17331723
      supporting_text: Inhibitory Gli3 activity negatively regulates Wnt/beta-catenin signaling.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16611247
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:16611247
      supporting_text: Human scribble, a novel tumor suppressor identified as a target of high-risk HPV E6 for ubiquitin-mediated degradation, interacts with adenomatous polyposis coli.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19458197
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:19458197
      supporting_text: Scribble interacts with beta-catenin to localize synaptic vesicles to synapses.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10954424
  review:
    summary: Bare 'protein binding' is uninformative; beta-catenin's meaningful interactions are captured by specific cadherin/alpha-catenin/TCF binding terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic MF over-annotation.
    supported_by:
    - reference_id: PMID:10954424
      supporting_text: The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1.
- term:
    id: GO:0019903
    label: protein phosphatase binding
  evidence_type: IPI
  original_reference_id: PMID:16973135
  review:
    summary: Protein-phosphatase binding (e.g. PTPN6/PTPRJ) regulates tyrosine-phosphorylation of junctional beta-catenin, a regulatory interaction.
    action: KEEP_AS_NON_CORE
    reason: Regulatory partner; IBA/IPI, non-core.
    supported_by:
    - reference_id: PMID:16973135
      supporting_text: Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT).
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-209096
  review:
    summary: Beta-catenin has a cytosolic pool subject to destruction-complex regulation and Wnt-dependent stabilization.
    action: ACCEPT
    reason: Genuine pool; IDA/TAS-supported.
references:
- id: GO_REF:0000008
  title: Gene Ontology annotation by the MGI curatorial staff, curated orthology
  findings: []
- id: PMID:10662781
  title: Requirement for beta-catenin in anterior-posterior axis formation in mice.
  findings: []
- id: PMID:11371349
  title: beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin.
  findings: []
- id: PMID:12194849
  title: Formation of multiple hearts in mice following deletion of beta-catenin in the embryonic endoderm.
  findings: []
- id: PMID:12235125
  title: Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor.
  findings: []
- id: PMID:12464179
  title: Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development.
  findings: []
- id: PMID:12717450
  title: A role for Wnt signalling in self-renewal of haematopoietic stem cells.
  findings: []
- id: PMID:12813461
  title: Activation of beta-catenin in prostate epithelium induces hyperplasias and squamous transdifferentiation.
  findings: []
- id: PMID:12885771
  title: beta-Catenin is required for specification of proximal/distal cell fate during lung morphogenesis.
  findings: []
- id: PMID:12923052
  title: Genetic interaction between Wnt/beta-catenin and BMP receptor signaling during formation of the AER and the dorsal-ventral axis in the limb.
  findings: []
- id: PMID:12975353
  title: The conditional inactivation of the beta-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility.
  findings: []
- id: PMID:14608382
  title: Deletion of beta-catenin impairs T cell development.
  findings: []
- id: PMID:14622577
  title: Role of beta-catenin in synaptic vesicle localization and presynaptic assembly.
  findings: []
- id: PMID:15131783
  title: 'Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin.'
  findings: []
- id: PMID:15708565
  title: Effects of canonical Wnt signaling on dorso-ventral specification of the mouse telencephalon.
  findings: []
- id: PMID:15866163
  title: Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
  findings: []
- id: PMID:15866165
  title: Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
  findings: []
- id: PMID:15907834
  title: Wnt/beta-catenin signaling acts upstream of N-myc, BMP4, and FGF signaling to regulate proximal-distal patterning in the lung.
  findings: []
- id: PMID:16040629
  title: Beta-catenin regulates differentiation of respiratory epithelial cells in vivo.
  findings: []
- id: PMID:16102745
  title: 'The duality of beta-catenin function: a requirement in lens morphogenesis and signaling suppression of lens fate in periocular ectoderm.'
  findings: []
- id: PMID:16478791
  title: APC inhibits ERK pathway activation and cellular proliferation induced by RAS.
  findings: []
- id: PMID:16621792
  title: 'Membrane localization of adenomatous polyposis coli protein at cellular protrusions: targeting sequences and regulation by beta-catenin.'
  findings: []
- id: PMID:16818445
  title: Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis.
  findings: []
- id: PMID:17537789
  title: Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development.
  findings: []
- id: PMID:17706960
  title: Persistent expression of stabilized beta-catenin delays maturation of radial glial cells into intermediate progenitors.
  findings: []
- id: PMID:18231602
  title: Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.
  findings: []
- id: PMID:18533146
  title: An FGF-WNT gene regulatory network controls lung mesenchyme development.
  findings: []
- id: PMID:18635608
  title: Tissue-specific requirements of beta-catenin in external genitalia development.
  findings: []
- id: PMID:19023080
  title: Canonical Wnt signaling regulates organ-specific assembly and differentiation of CNS vasculature.
  findings: []
- id: PMID:19060336
  title: A Wnt7b-dependent pathway regulates the orientation of epithelial cell division and establishes the cortico-medullary axis of the mammalian kidney.
  findings: []
- id: PMID:19129494
  title: Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis.
  findings: []
- id: PMID:19154719
  title: Nrarp coordinates endothelial Notch and Wnt signaling to control vessel density in angiogenesis.
  findings: []
- id: PMID:19204372
  title: Both the RGS domain and the six C-terminal amino acids of mouse Axin are required for normal embryogenesis.
  findings: []
- id: PMID:19503085
  title: HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction.
  findings: []
- id: PMID:19619491
  title: Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
  findings: []
- id: PMID:19620969
  title: A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate.
  findings: []
- id: PMID:19690384
  title: Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.
  findings: []
- id: PMID:20043884
  title: Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling within the Apical Ectodermal Ridge (AER) regulates interdigit formation.
  findings: []
- id: PMID:20454446
  title: WNT4/beta-catenin pathway maintains female germ cell survival by inhibiting activin betaB in the mouse fetal ovary.
  findings: []
- id: PMID:20503375
  title: Expression analysis of an evolutionarily conserved metallophosphodiesterase gene, Mpped1, in the normal and beta-catenin-deficient malformed dorsal telencephalon.
  findings: []
- id: PMID:21937711
  title: ASPM regulates Wnt signaling pathway activity in the developing brain.
  findings: []
- id: PMID:22102609
  title: Increased Ξ²-catenin activity in the anterior neural plate induces ectopic mid-hindbrain characteristics.
  findings: []
- id: PMID:22723415
  title: Wnt/Ξ²-catenin signaling regulates telomerase in stem cells and cancer cells.
  findings: []
- id: PMID:23824574
  title: Wnt/Ξ²-catenin signalling regulates Sox17 expression and is essential for organizer and endoderm formation in the mouse.
  findings: []
- id: PMID:25083995
  title: Canonical WNT signaling components in vascular development and barrier formation.
  findings: []
- id: PMID:28463231
  title: Disruption of lineage specification in adult pulmonary mesenchymal progenitor cells promotes microvascular dysfunction.
  findings: []
- id: PMID:8582267
  title: Lack of beta-catenin affects mouse development at gastrulation.
  findings: []
- id: PMID:9230313
  title: The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara.
  findings: []
- id: GO_REF:0000119
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs.
  findings: []
- id: PMID:10631168
  title: Hippocampus development and generation of dentate gyrus granule cells is regulated by LEF1.
  findings: []
- id: PMID:12551949
  title: Lymphoid enhancer factor-1 and beta-catenin inhibit Runx2-dependent transcriptional activation of the osteocalcin promoter.
  findings: []
- id: PMID:12569130
  title: Ectodermal Wnt3/beta-catenin signaling is required for the establishment and maintenance of the apical ectodermal ridge.
  findings: []
- id: PMID:15024079
  title: Brn-2 expression controls melanoma proliferation and is directly regulated by beta-catenin.
  findings: []
- id: PMID:15371327
  title: Wnt/beta-catenin signaling is sufficient and necessary for synovial joint formation.
  findings: []
- id: PMID:15576404
  title: Sequential roles of Hedgehog and Wnt signaling in osteoblast development.
  findings: []
- id: PMID:15729346
  title: Pax3 functions at a nodal point in melanocyte stem cell differentiation.
  findings: []
- id: PMID:15778706
  title: Wnt signalling induces maturation of Paneth cells in intestinal crypts.
  findings: []
- id: PMID:15781477
  title: Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation.
  findings: []
- id: PMID:15802266
  title: Essential role of beta-catenin in postnatal bone acquisition.
  findings: []
- id: PMID:16025118
  title: Loss of adenomatous polyposis coli gene function disrupts thymic development.
  findings: []
- id: PMID:16192304
  title: Beta-catenin is essential for pancreatic acinar but not islet development.
  findings: []
- id: PMID:16581771
  title: CCN1/Cyr61 is regulated by the canonical Wnt signal and plays an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells.
  findings: []
- id: PMID:16678101
  title: Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
  findings: []
- id: PMID:16936075
  title: The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 expression during somitogenesis.
  findings: []
- id: PMID:17055474
  title: The stabilization of beta-catenin leads to impaired primordial germ cell development via aberrant cell cycle progression.
  findings: []
- id: PMID:17128274
  title: Wnt-beta-catenin signaling initiates taste papilla development.
  findings: []
- id: PMID:17532316
  title: Essential roles of mesenchyme-derived beta-catenin in mouse MΓΌllerian duct morphogenesis.
  findings: []
- id: PMID:17767158
  title: Modulation of morphogenesis by noncanonical Wnt signaling requires ATF/CREB family-mediated transcriptional activation of TGFbeta2.
  findings: []
- id: PMID:18316368
  title: Protein encoded by the Axin(Fu) allele effectively down-regulates Wnt signaling but exerts a dominant negative effect on c-Jun N-terminal kinase signaling.
  findings: []
- id: PMID:18692041
  title: 'Bmp4 is required for tracheal formation: a novel mouse model for tracheal agenesis.'
  findings: []
- id: PMID:19056892
  title: A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors.
  findings: []
- id: PMID:19282366
  title: Genetic interactions of the androgen and Wnt/beta-catenin pathways for the masculinization of external genitalia.
  findings: []
- id: PMID:19515974
  title: Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS.
  findings: []
- id: PMID:19686689
  title: Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut.
  findings: []
- id: PMID:19718027
  title: Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia.
  findings: []
- id: PMID:19805295
  title: beta-Catenin promotes respiratory progenitor identity in mouse foregut.
  findings: []
- id: PMID:20159597
  title: Characterization and in vivo pharmacological rescue of a Wnt2-Gata6 pathway required for cardiac inflow tract development.
  findings: []
- id: PMID:20627076
  title: The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/Notch signaling.
  findings: []
- id: PMID:21075118
  title: Biochemical and structural characterization of Ξ²-catenin interactions with nonphosphorylated and CK2-phosphorylated Lef-1.
  findings: []
- id: PMID:21750544
  title: The Wnt3a/Ξ²-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program.
  findings: []
- id: PMID:22956852
  title: Integration of Ξ²-catenin, sirtuin, and FOXO signaling protects from mutant huntingtin toxicity.
  findings: []
- id: PMID:24309208
  title: Wnt/Ξ²-catenin signaling in dermal condensates is required for hair follicle formation.
  findings: []
- id: PMID:27713508
  title: Conditional Knockout of Breast Carcinoma Amplified Sequence 2 (BCAS2) in Mouse Forebrain Causes Dendritic Malformation via Ξ²-catenin.
  findings: []
- id: PMID:31222549
  title: The Shisa3 knockout mouse exhibits normal bone phenotype.
  findings: []
- id: GO_REF:0000024
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000033
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000043
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000044
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000096
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000117
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000120
  title: 'TODO: Fetch title'
  findings: []
- id: PMID:10318824
  title: Functional domains of axin. Importance of the C terminus as an oligomerization domain.
  findings: []
- id: PMID:10330403
  title: Domains of axin involved in protein-protein interactions, Wnt pathway inhibition, and intracellular localization.
  findings: []
- id: PMID:10481074
  title: A GSK3-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed phosphorylation of axin and beta-catenin.
  findings: []
- id: PMID:10873669
  title: Identification of a novel beta-catenin-interacting protein.
  findings: []
- id: PMID:10882138
  title: Structure of the dimerization and beta-catenin-binding region of alpha-catenin.
  findings: []
- id: PMID:10898789
  title: Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein.
  findings: []
- id: PMID:10954424
  title: The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1.
  findings: []
- id: PMID:11104755
  title: Substitution of a glycogen synthase kinase-3beta phosphorylation site in presenilin 1 separates presenilin function from beta-catenin signaling.
  findings: []
- id: PMID:11121423
  title: The cadherin cytoplasmic domain is unstructured in the absence of beta-catenin. A possible mechanism for regulating cadherin turnover.
  findings: []
- id: PMID:11262227
  title: Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
  findings: []
- id: PMID:11348595
  title: The structure of the beta-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by beta-catenin.
  findings: []
- id: PMID:11590244
  title: 'alphaT-catenin: a novel tissue-specific beta-catenin-binding protein mediating strong cell-cell adhesion.'
  findings: []
- id: PMID:11731229
  title: FAM deubiquitylating enzyme is essential for preimplantation mouse embryo development.
  findings: []
- id: PMID:11731231
  title: Dynamic expression and nuclear accumulation of beta-catenin during the development of hair follicle-derived structures.
  findings: []
- id: PMID:11731265
  title: Expression of Tcf/Lef and sFrp and localization of beta-catenin in the developing mouse lung.
  findings: []
- id: PMID:11872843
  title: Colorectal cancer in mice genetically deficient in the mucin Muc2.
  findings: []
- id: PMID:12040017
  title: 'Mouse mammary epithelial cells express the Na-K-Cl cotransporter, NKCC1: characterization, localization, and involvement in ductal development and morphogenesis.'
  findings: []
- id: PMID:12055200
  title: Regulation of Wnt signaling during adipogenesis.
  findings: []
- id: PMID:12181493
  title: TCL1 participates in early embryonic development and is overexpressed in human seminomas.
  findings: []
- id: PMID:12203715
  title: Localization of the novel Xin protein to the adherens junction complex in cardiac and skeletal muscle during development.
  findings: []
- id: PMID:12408825
  title: ICAT inhibits beta-catenin binding to Tcf/Lef-family transcription factors and the general coactivator p300 using independent structural modules.
  findings: []
- id: PMID:12421363
  title: Axin negatively affects tau phosphorylation by glycogen synthase kinase 3beta.
  findings: []
- id: PMID:12432063
  title: Protein kinase CKII regulates the interaction of beta-catenin with alpha-catenin and its protein stability.
  findings: []
- id: PMID:12494996
  title: Loss of desmoglein 2 suggests essential functions for early embryonic development and proliferation of embryonal stem cells.
  findings: []
- id: PMID:12611902
  title: Regulation of the SHP-2 tyrosine phosphatase by a novel cholesterol- and cell confluence-dependent mechanism.
  findings: []
- id: PMID:12695331
  title: NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions.
  findings: []
- id: PMID:12861022
  title: T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors.
  findings: []
- id: PMID:12874278
  title: The PDZ protein tax-interacting protein-1 inhibits beta-catenin transcriptional activity and growth of colorectal cancer cells.
  findings: []
- id: PMID:12949260
  title: Wnt4 overexpression disrupts normal testicular vasculature and inhibits testosterone synthesis by repressing steroidogenic factor 1/beta-catenin synergy.
  findings: []
- id: PMID:14597196
  title: Overexpression of Sonic Hedgehog suppresses embryonic hair follicle morphogenesis.
  findings: []
- id: PMID:14625387
  title: Foxj1 is required for apical localization of ezrin in airway epithelial cells.
  findings: []
- id: PMID:14647292
  title: Mammalian formin-1 participates in adherens junctions and polymerization of linear actin cables.
  findings: []
- id: PMID:14657280
  title: 'Lamellipodium extension and cadherin adhesion: two cell responses to cadherin activation relying on distinct signalling pathways.'
  findings: []
- id: PMID:14687547
  title: RORalpha coordinates reciprocal signaling in cerebellar development through sonic hedgehog and calcium-dependent pathways.
  findings: []
- id: PMID:14691142
  title: alpha3beta1 integrin-CD151, a component of the cadherin-catenin complex, regulates PTPmu expression and cell-cell adhesion.
  findings: []
- id: PMID:14758363
  title: The hyh mutation uncovers roles for alpha Snap in apical protein localization and control of neural cell fate.
  findings: []
- id: PMID:14960280
  title: Ozz-E3, a muscle-specific ubiquitin ligase, regulates beta-catenin degradation during myogenesis.
  findings: []
- id: PMID:14981260
  title: Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of beta-catenin.
  findings: []
- id: PMID:15023525
  title: Ksp-cadherin is a functional cell-cell adhesion molecule related to LI-cadherin.
  findings: []
- id: PMID:15037549
  title: Loss of cell polarity causes severe brain dysplasia in Lgl1 knockout mice.
  findings: []
- id: PMID:15057752
  title: Beta-catenin is temporally regulated during normal liver development.
  findings: []
- id: PMID:15110721
  title: Sox1 acts through multiple independent pathways to promote neurogenesis.
  findings: []
- id: PMID:15148305
  title: Mammalian Fat1 cadherin regulates actin dynamics and cell-cell contact.
  findings: []
- id: PMID:15226261
  title: Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization.
  findings: []
- id: PMID:15292239
  title: Defects in cell adhesion and the visceral endoderm following ablation of nonmuscle myosin heavy chain II-A in mice.
  findings: []
- id: PMID:15314168
  title: Cyclin D1 genetic heterozygosity regulates colonic epithelial cell differentiation and tumor number in ApcMin mice.
  findings: []
- id: PMID:15327768
  title: Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation.
  findings: []
- id: PMID:15525667
  title: Stabilization of beta-catenin in the mouse zygote leads to premature epithelial-mesenchymal transition in the epiblast.
  findings: []
- id: PMID:15574752
  title: Role of a BCL9-related beta-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling.
  findings: []
- id: PMID:15645444
  title: Gene expression profile analysis of mouse colon embryonic development.
  findings: []
- id: PMID:15673614
  title: Wnt10b deficiency promotes coexpression of myogenic and adipogenic programs in myoblasts.
  findings: []
- id: PMID:15775979
  title: E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions.
  findings: []
- id: PMID:15834408
  title: The KIF3 motor transports N-cadherin and organizes the developing neuroepithelium.
  findings: []
- id: PMID:15905404
  title: Functional interaction between beta-catenin and FOXO in oxidative stress signaling.
  findings: []
- id: PMID:15908431
  title: MAGI1 recruits Dll1 to cadherin-based adherens junctions and stabilizes it on the cell surface.
  findings: []
- id: PMID:15987773
  title: Forkhead box A1 regulates prostate ductal morphogenesis and promotes epithelial cell maturation.
  findings: []
- id: PMID:16199027
  title: Vezatin, a protein associated to adherens junctions, is required for mouse blastocyst morphogenesis.
  findings: []
- id: PMID:16249236
  title: Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network.
  findings: []
- id: PMID:16293619
  title: 'Thermodynamics of beta-catenin-ligand interactions: the roles of the N- and C-terminal tails in modulating binding affinity.'
  findings: []
- id: PMID:16364283
  title: Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development.
  findings: []
- id: PMID:16368433
  title: Deficient E-cadherin adhesion in C57BL/6J-Min/+ mice is associated with increased tyrosine kinase activity and RhoA-dependent actomyosin contractility.
  findings: []
- id: PMID:16418220
  title: Desmocollin 3 is required for pre-implantation development of the mouse embryo.
  findings: []
- id: PMID:16439479
  title: Foxf1 and Foxf2 control murine gut development by limiting mesenchymal Wnt signaling and promoting extracellular matrix production.
  findings: []
- id: PMID:16481394
  title: 'The transitional junction: a new functional subcellular domain at the intercalated disc.'
  findings: []
- id: PMID:16489008
  title: Patched1 functions as a gatekeeper by promoting cell cycle progression.
  findings: []
- id: PMID:16611247
  title: Human scribble, a novel tumor suppressor identified as a target of high-risk HPV E6 for ubiquitin-mediated degradation, interacts with adenomatous polyposis coli.
  findings: []
- id: PMID:16678815
  title: Lef1 is required for the transition of Wnt signaling from mesenchymal to epithelial cells in the mouse embryonic mammary gland.
  findings: []
- id: PMID:16740478
  title: Apc tumor suppressor gene is the "zonation-keeper" of mouse liver.
  findings: []
- id: PMID:16858399
  title: C3G regulates the size of the cerebral cortex neural precursor population.
  findings: []
- id: PMID:16892058
  title: The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface.
  findings: []
- id: PMID:16962386
  title: 'Tissue, cellular and sub-cellular localization of the Vangl2 protein during embryonic development: effect of the Lp mutation.'
  findings: []
- id: PMID:16973135
  title: Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT).
  findings: []
- id: PMID:16989802
  title: Levels of mesenchymal FGFR2 signaling modulate smooth muscle progenitor cell commitment in the lung.
  findings: []
- id: PMID:17130295
  title: Distinct subdomain organization and molecular composition of a tight junction with adherens junction features.
  findings: []
- id: PMID:17331723
  title: Inhibitory Gli3 activity negatively regulates Wnt/beta-catenin signaling.
  findings: []
- id: PMID:17535849
  title: A unique and specific interaction between alphaT-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs.
  findings: []
- id: PMID:17544522
  title: Targeted disruption of the murine large nuclear KIAA1440/Ints1 protein causes growth arrest in early blastocyst stage embryos and eventual apoptotic cell death.
  findings: []
- id: PMID:17560563
  title: Fgf10 dosage is critical for the amplification of epithelial cell progenitors and for the formation of multiple mesenchymal lineages during lung development.
  findings: []
- id: PMID:17596282
  title: Unique mechanisms of growth regulation and tumor suppression upon Apc inactivation in the pancreas.
  findings: []
- id: PMID:17615359
  title: Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88.
  findings: []
- id: PMID:17666436
  title: Shroom2, a myosin-VIIa- and actin-binding protein, directly interacts with ZO-1 at tight junctions.
  findings: []
- id: PMID:17671182
  title: Haploinsufficiency of KrΓΌppel-like factor 4 promotes adenomatous polyposis coli dependent intestinal tumorigenesis.
  findings: []
- id: PMID:17920587
  title: FERM protein EPB41L5 is a novel member of the mammalian CRB-MPP5 polarity complex.
  findings: []
- id: PMID:18202148
  title: Cooperative control via lymphoid enhancer factor 1/T cell factor 3 and estrogen receptor-alpha for uterine gene regulation by estrogen.
  findings: []
- id: PMID:18632848
  title: SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability.
  findings: []
- id: PMID:18636119
  title: Coxsackievirus and adenovirus receptor (CAR) mediates atrioventricular-node function and connexin 45 localization in the murine heart.
  findings: []
- id: PMID:18816447
  title: 'Diverse roles of E-cadherin in the morphogenesis of the submandibular gland: insights into the formation of acinar and ductal structures.'
  findings: []
- id: PMID:18978355
  title: Overexpression of TEAD-1 in transgenic mouse striated muscles produces a slower skeletal muscle contractile phenotype.
  findings: []
- id: PMID:19107203
  title: Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling.
  findings: []
- id: PMID:19112489
  title: Gata3 acts downstream of beta-catenin signaling to prevent ectopic metanephric kidney induction.
  findings: []
- id: PMID:19122665
  title: Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis.
  findings: []
- id: PMID:19151727
  title: Regulation of cardiovascular development and integrity by the heart of glass-cerebral cavernous malformation protein pathway.
  findings: []
- id: PMID:19213727
  title: Wnt11 promotes osteoblast maturation and mineralization through R-spondin 2.
  findings: []
- id: PMID:19458197
  title: Scribble interacts with beta-catenin to localize synaptic vesicles to synapses.
  findings: []
- id: PMID:19497282
  title: Wnt7a activates the planar cell polarity pathway to drive the symmetric expansion of satellite stem cells.
  findings: []
- id: PMID:19725955
  title: Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification.
  findings: []
- id: PMID:19796622
  title: Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors.
  findings: []
- id: PMID:19850029
  title: A critical role for sFRP proteins in maintaining caudal neural tube closure in mice via inhibition of BMP signaling.
  findings: []
- id: PMID:19966784
  title: Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closure.
  findings: []
- id: PMID:20016102
  title: The small GTPase Rac1 regulates auditory hair cell morphogenesis.
  findings: []
- id: PMID:20089884
  title: Milk secretion and ejection are impaired in the mammary gland of mice harboring a Cx43 mutant while expression and localization of tight and adherens junction proteins remain unchanged.
  findings: []
- id: PMID:20299672
  title: Epicardial-myocardial signaling directing coronary vasculogenesis.
  findings: []
- id: PMID:20300119
  title: Conductin/axin2 and Wnt signalling regulates centrosome cohesion.
  findings: []
- id: PMID:20371816
  title: LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1g) in thalamic neurons of the adult brain.
  findings: []
- id: PMID:20399730
  title: The apical complex couples cell fate and cell survival to cerebral cortical development.
  findings: []
- id: PMID:20413591
  title: The TRPV4 channel contributes to intercellular junction formation in keratinocytes.
  findings: []
- id: PMID:20531388
  title: Mutant huntingtin-impaired degradation of beta-catenin causes neurotoxicity in Huntington's disease.
  findings: []
- id: PMID:20802155
  title: Sox17 modulates Wnt3A/beta-catenin-mediated transcriptional activation of the Lef-1 promoter.
  findings: []
- id: PMID:20837657
  title: Abelson family kinases regulate Frizzled planar cell polarity signaling via Dsh phosphorylation.
  findings: []
- id: PMID:21103407
  title: The leukemia-associated Mllt10/Af10-Dot1l are Tcf4/Ξ²-catenin coactivators essential for intestinal homeostasis.
  findings: []
- id: PMID:21262216
  title: The zinc finger transcription factors Osr1 and Osr2 control synovial joint formation.
  findings: []
- id: PMID:21325504
  title: Frizzled3 is required for neurogenesis and target innervation during sympathetic nervous system development.
  findings: []
- id: PMID:21350016
  title: Canonical Wnt9b signaling balances progenitor cell expansion and differentiation during kidney development.
  findings: []
- id: PMID:21377456
  title: Grainyhead-like 2 regulates neural tube closure and adhesion molecule expression during neural fold fusion.
  findings: []
- id: PMID:21393547
  title: A polarized epithelium organized by beta- and alpha-catenin predates cadherin and metazoan origins.
  findings: []
- id: PMID:21512031
  title: Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size.
  findings: []
- id: PMID:21552260
  title: Nemo kinase phosphorylates Ξ²-catenin to promote ommatidial rotation and connects core PCP factors to E-cadherin-Ξ²-catenin.
  findings: []
- id: PMID:21730140
  title: Ezrin-mediated apical integrity is required for intestinal homeostasis.
  findings: []
- id: PMID:21751375
  title: Functional analysis of novel phosphorylation sites of CREB-binding protein using mass spectrometry and mammalian two-hybrid assays.
  findings: []
- id: PMID:21752258
  title: 'A Wnt1 regulated Frizzled-1/Ξ²-Catenin signaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: Therapeutical relevance for neuron survival and neuroprotection.'
  findings: []
- id: PMID:21991325
  title: RSPO1/Ξ²-catenin signaling pathway regulates oogonia differentiation and entry into meiosis in the mouse fetal ovary.
  findings: []
- id: PMID:21991385
  title: Adhesion protein VSIG1 is required for the proper differentiation of glandular gastric epithelia.
  findings: []
- id: PMID:22083958
  title: Histone H1 recruitment by CHD8 is essential for suppression of the Wnt-Ξ²-catenin signaling pathway.
  findings: []
- id: PMID:22139371
  title: Bardet-Biedl syndrome 3 (Bbs3) knockout mouse model reveals common BBS-associated phenotypes and Bbs3 unique phenotypes.
  findings: []
- id: PMID:22645310
  title: Prolyl isomerase Pin1 regulates neuronal differentiation via Ξ²-catenin.
  findings: []
- id: PMID:22665494
  title: mrhl RNA, a long noncoding RNA, negatively regulates Wnt signaling through its protein partner Ddx5/p68 in mouse spermatogonial cells.
  findings: []
- id: PMID:22899650
  title: LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6.
  findings: []
- id: PMID:23266329
  title: Kruppel-like factor 5 controls villus formation and initiation of cytodifferentiation in the embryonic intestinal epithelium.
  findings: []
- id: PMID:23273993
  title: Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties.
  findings: []
- id: PMID:23377854
  title: Physiological role of Ξ²-catenin/TCF signaling in neurons of the adult brain.
  findings: []
- id: PMID:23460868
  title: Ξ²-catenin is essential for efficient in vitro premyogenic mesoderm formation but can be partially compensated by retinoic acid signalling.
  findings: []
- id: PMID:23610556
  title: A positive feedback loop involving Gcm1 and Fzd5 directs chorionic branching morphogenesis in the placenta.
  findings: []
- id: PMID:23740243
  title: Activation of the transcription factor GLI1 by WNT signaling underlies the role of SULFATASE 2 as a regulator of tissue regeneration.
  findings: []
- id: PMID:23856522
  title: Jmjd3 controls mesodermal and cardiovascular differentiation of embryonic stem cells.
  findings: []
- id: PMID:23863479
  title: Tumor suppressor Nf2 limits expansion of the neural progenitor pool by inhibiting Yap/Taz transcriptional coactivators.
  findings: []
- id: PMID:24046456
  title: Flotillin microdomains stabilize cadherins at cell-cell junctions.
  findings: []
- id: PMID:24191021
  title: Sox9 plays multiple roles in the lung epithelium during branching morphogenesis.
  findings: []
- id: PMID:24338362
  title: POPX2 phosphatase regulates the KIF3 kinesin motor complex.
  findings: []
- id: PMID:24681597
  title: Kindlin-1 controls Wnt and TGF-Ξ² availability to regulate cutaneous stem cell proliferation.
  findings: []
- id: PMID:24847765
  title: From inception to output, Tcf1 and Lef1 safeguard development of T cells and innate immune cells.
  findings: []
- id: PMID:25009587
  title: Depletion of canonical Wnt signaling components has a neuroprotective effect on midbrain dopaminergic neurons in an MPTP-induced mouse model of Parkinson's disease.
  findings: []
- id: PMID:25232112
  title: Dlg5 regulates dendritic spine formation and synaptogenesis by controlling subcellular N-cadherin localization.
  findings: []
- id: PMID:25535395
  title: Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway.
  findings: []
- id: PMID:25873176
  title: TGIF governs a feed-forward network that empowers Wnt signaling to drive mammary tumorigenesis.
  findings: []
- id: PMID:25961718
  title: Resveratrol-Induced Vascular Progenitor Differentiation towards Endothelial Lineage via MiR-21/Akt/Ξ²-Catenin Is Protective in Vessel Graft Models.
  findings: []
- id: PMID:25979161
  title: Transmembrane protein 64 reciprocally regulates osteoblast and adipocyte differentiation by modulating Wnt/Ξ²-catenin signaling.
  findings: []
- id: PMID:26371318
  title: Lhx2 regulates the timing of Ξ²-catenin-dependent cortical neurogenesis.
  findings: []
- id: PMID:26787558
  title: SPECC1L deficiency results in increased adherens junction stability and reduced cranial neural crest cell delamination.
  findings: []
- id: PMID:26893351
  title: The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis.
  findings: []
- id: PMID:27015268
  title: Plakophilin-1, a Novel Wnt Signaling Regulator, Is Critical for Tooth Development and Ameloblast Differentiation.
  findings: []
- id: PMID:27375112
  title: Antagonistic Regulation of Intercellular Cohesion by Plakophilins 1 and 3.
  findings: []
- id: PMID:28641114
  title: A Critical Role of Presynaptic Cadherin/Catenin/p140Cap Complexes in Stabilizing Spines and Functional Synapses in the Neocortex.
  findings: []
- id: PMID:29148101
  title: Homeobox protein MSX-1 inhibits expression of bone morphogenetic protein 2, bone morphogenetic protein 4, and lymphoid enhancer-binding factor 1 via Wnt/Ξ²-catenin signaling to prevent differentiation of dental mesenchymal cells during the late bell stage.
  findings: []
- id: PMID:29211732
  title: The mouse Jhy gene regulates ependymal cell differentiation and ciliogenesis.
  findings: []
- id: PMID:30389919
  title: ARTS mediates apoptosis and regeneration of the intestinal stem cell niche.
  findings: []
- id: PMID:30478225
  title: TBX2 and TBX3 act downstream of canonical WNT signaling in patterning and differentiation of the mouse ureteric mesenchyme.
  findings: []
- id: PMID:30659184
  title: Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis.
  findings: []
- id: PMID:31073040
  title: LMBR1L regulates lymphopoiesis through Wnt/Ξ²-catenin signaling.
  findings: []
- id: PMID:32533114
  title: ADNP promotes neural differentiation by modulating Wnt/Ξ²-catenin signaling.
  findings: []
- id: PMID:32868762
  title: The cellular and molecular landscape of hypothalamic patterning and differentiation from embryonic to late postnatal development.
  findings: []
- id: PMID:8555428
  title: Immunotoxicologic effects of ethylene dibromide in the mouse and their modulation by the estrous cycle.
  findings: []
- id: PMID:8821035
  title: Expression of catenins during mouse embryonic development and in adult tissues.
  findings: []
- id: PMID:8853988
  title: Expression and cell membrane localization of catenins during mouse preimplantation development.
  findings: []
- id: PMID:8909549
  title: The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones.
  findings: []
- id: PMID:9264463
  title: A specific domain in alpha-catenin mediates binding to beta-catenin or plakoglobin.
  findings: []
- id: PMID:9488439
  title: Two members of the Tcf family implicated in Wnt/beta-catenin signaling during embryogenesis in the mouse.
  findings: []
- id: PMID:9554852
  title: Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta.
  findings: []
- id: PMID:9950951
  title: Nuclear localization of beta-catenin and loss of apical brush border actin in cystic tubules of bcl-2 -/- mice.
  findings: []
- id: Reactome:R-MMU-209096
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-MMU-9735211
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-MMU-9754284
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-MMU-9773219
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-MMU-9793864
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-MMU-9794042
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-MMU-9823738
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-MMU-9824206
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-MMU-9824277
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-MMU-9824278
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-MMU-9860515
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-MMU-9860560
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-MMU-9860569
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-MMU-9863577
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-NUL-9761463
  title: 'TODO: Fetch title'
  findings: []
- id: file:mouse/Ctnnb1/Ctnnb1-deep-research-falcon.md
  title: Falcon deep research synthesis for mouse Ctnnb1
  findings:
  - statement: >-
      Beta-catenin has two core molecular roles: cadherin-catenin adhesion
      at adherens junctions and canonical Wnt/TCF transcriptional coactivation.
    supporting_text: beta-catenin is widely characterized as a multifunctional protein that supports adherens junction integrity by binding the cytoplasmic tail of E-cadherin and acts as the central transcriptional effector of canonical Wnt/beta-catenin signaling.
  - statement: Ctnnb1 is a non-enzymatic adaptor and transcriptional coactivator whose functions are driven by partner-specific protein interactions.
    supporting_text: Ctnnb1/beta-catenin is best annotated as a non-enzymatic adaptor and transcriptional co-activator whose primary molecular functions arise from protein-protein interactions rather than catalytic activity.
core_functions:
- description: Beta-catenin binds cadherins and alpha-catenin in adherens junctions to support cadherin-mediated cell-cell adhesion.
  molecular_function:
    id: GO:0045296
    label: cadherin binding
  directly_involved_in:
  - id: GO:0098609
    label: cell-cell adhesion
  - id: GO:0044331
    label: cell-cell adhesion mediated by cadherin
  locations:
  - id: GO:0005912
    label: adherens junction
  - id: GO:0005911
    label: cell-cell junction
  - id: GO:0005886
    label: plasma membrane
  in_complex:
    id: GO:0016342
    label: catenin complex
  supported_by:
  - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
    supporting_text: Beta-catenin is a key cytoplasmic component of the cadherin-catenin complex at adherens junctions
  - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research-falcon.md
    supporting_text: beta-catenin supports adherens junction integrity by binding the cytoplasmic tail of E-cadherin and linking to alpha-catenin/actin-associated structures.
- description: Stabilized beta-catenin acts with TCF/LEF transcription factors as a transcriptional coactivator in canonical Wnt signaling.
  molecular_function:
    id: GO:0003713
    label: transcription coactivator activity
  directly_involved_in:
  - id: GO:0060070
    label: canonical Wnt signaling pathway
  - id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0005654
    label: nucleoplasm
  in_complex:
    id: GO:1990907
    label: beta-catenin-TCF complex
  supported_by:
  - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research.md
    supporting_text: In the nucleus, beta-catenin acts as a co-activator for TCF/LEF transcription factors
  - reference_id: file:mouse/Ctnnb1/Ctnnb1-deep-research-falcon.md
    supporting_text: beta-catenin acts as the central transcriptional effector of canonical Wnt/beta-catenin signaling, accumulating and entering the nucleus when stabilized to co-activate TCF/LEF-dependent transcription.
suggested_questions:
- question: How does Ξ²-catenin coordinate its dual roles in cell adhesion and Wnt signaling, and what mechanisms prevent crosstalk?
- question: What determines the tissue-specific requirements for Ξ²-catenin in development versus homeostasis?
- question: How do different Ξ²-catenin mutations lead to distinct developmental disorders and cancer types?
- question: What role does Ξ²-catenin play in stem cell maintenance and differentiation across different tissue types?
suggested_experiments:
- description: Single-cell RNA sequencing of tissues with conditional Ξ²-catenin knockout to map cell-type-specific transcriptional programs
- description: Super-resolution microscopy to study Ξ²-catenin dynamics between adherens junctions and the nucleus during Wnt signaling
- description: Cryo-EM structural determination of Ξ²-catenin in complex with different binding partners like cadherins and TCF/LEF
- description: Lineage tracing in mouse models to study Ξ²-catenin function in stem cell fate decisions during development and regeneration

πŸ”— Related Resources

πŸ“Š View Pathway Visualization Interactive pathway diagram with detailed annotations