CDH1

Summary: IBA projection from the PANTHER classical cadherin family tree (PTHR24027) via GO_REF:0000033. E-cadherin contributes to epithelial cell morphogenesis because cadherin-mediated adhesion shapes epithelial cells and is required to establish and maintain epithelial architecture. However, cell morphogenesis is a broad downstream outcome of the core adhesion and junction-organizing activity rather than a distinct core function. The precise core CDH1 processes (calcium-dependent homophilic cell-cell adhesion, cadherin-mediated adhesion, adherens junction organization) are captured by other rows in this file.

Reason: Real but general developmental/cellular outcome downstream of the core adhesion function; the precise core processes (GO:0044331 cell-cell adhesion mediated by cadherin, GO:0034332 adherens junction organization) are ACCEPTed elsewhere in this review.

Summary: IBA projection from the PANTHER cadherin family tree (PTHR24027) via GO_REF:0000033. E-cadherin participates in cell migration processes — it is retained at junctions during collective epithelial migration such as wound healing, and conversely its loss drives the epithelial-mesenchymal transition that licenses single-cell motility and invasion. The bare cell migration term carries no directionality, whereas the best-established directional CDH1 role is suppression of single-cell migration/invasion, separately captured by the IMP GO:0030336 (negative regulation of cell migration) row in this file (PMID:16882694). The generic involved_in cell-migration inference is therefore a real but non-core, context-dependent association.

Reason: Generic non-directional migration term; the core CDH1 activity is cell-cell adhesion rather than migration per se, and the directional regulatory role (suppression of migration/invasion) is captured by GO:0030336 elsewhere in the file.

Summary: IBA projection from the PANTHER classical cadherin family tree (PTHR24027) via GO_REF:0000033. E-cadherin nucleates assembly of epithelial cell-cell junctions — homophilic trans-engagement of E-cadherin ectodomains initiates cell-cell contact, and the cytoplasmic tail recruits the catenins that build the adherens junction and template subsequent tight-junction and desmosome formation. This is a core, well-established CDH1 function, consistent with the more specific GO:0034332 (adherens junction organization) row.

Reason: Core CDH1 biological process — E-cadherin is the founding adhesion receptor that initiates epithelial cell-cell junction assembly.

Summary: The broad PAINT cytoplasmic activity assertion is compatible with the cytoplasmic catenin-binding region and regulated intracellular E-cadherin pools.

Reason: Retain the ancestral is_active_in inference as non-core; this is not a new localization claim based only on the orientation of a transmembrane tail. Human catenin interactions and intracellular trafficking corroborate the broader biology, but a direct assay of catalytic or adhesion activity in free cytosol is not claimed. No target-specific loss of the inferred activity was established.

Summary: IBA projection from the PANTHER cadherin tree (PTHR24027) via GO_REF:0000033. The E-cadherin cytoplasmic catenin-binding domain directly binds beta-catenin (CTNNB1); this interaction links the cadherin to the actin cytoskeleton via alpha-catenin and is the molecular basis of the cadherin-catenin complex. Independently supported within this file by IPI/IDA evidence on this same term (PMID:18593713, Smad7 stabilizes beta-catenin binding to the E-cadherin complex; PMID:17620337) and by Reactome TAS rows describing CDH1-CTNNB1 complex formation.

Reason: Canonical core CDH1 molecular function — direct beta-catenin binding by the cadherin cytoplasmic tail is the defining interaction of the cadherin-catenin complex. Corroborated by IPI (PMID:18593713) and IDA (PMID:17620337) evidence on this exact term elsewhere in the file. Evolutionary note (action unchanged): the IBD sits on PANTHER node PTN008601603, which also covers a Monosiga brevicollis cadherin (A9V8Y4) that lacks the classical cadherin cytoplasmic domain (Pfam PF01049); classical cadherins and this domain are found only in animals. The IBA is correct for human CDH1, but the node is deeper than the evidence for the function.

Summary: IBA projection from the PANTHER classical cadherin tree (PTHR24027) via GO_REF:0000033. Cadherin-mediated cell-cell adhesion is the defining function of E-cadherin — calcium-dependent homophilic trans-interaction of ectodomains between adjacent epithelial cells. This is the central core CDH1 process. Independently supported in this file by IDA evidence on the same term (PMID:18593713) and by the crystallographic adhesion-architecture reference PMID:21300292.

Reason: Defining core biological process of E-cadherin — homophilic cadherin-mediated cell-cell adhesion. Corroborated by IDA evidence on this exact term (PMID:18593713) elsewhere in the file.

Summary: IBA projection (part_of) from the PANTHER cadherin tree (PTHR24027) via GO_REF:0000033. E-cadherin is the transmembrane core of the cadherin-catenin (catenin) complex; its cytoplasmic tail scaffolds beta-catenin and gamma-catenin and, via alpha-catenin, the actin cytoskeleton. Independently supported in this file by IDA evidence on the same GO:0016342 term (PMID:18593713).

Reason: Core CDH1 cellular component — E-cadherin is the obligate transmembrane component of the catenin complex. Corroborated by IDA evidence on this exact term (PMID:18593713) elsewhere in the file.

Summary: IBA projection from the PANTHER cadherin tree (PTHR24027) via GO_REF:0000033. E-cadherin engages in cadherin binding through calcium-dependent homophilic trans- and cis-interactions of its ectodomain (the EC1 strand-swap dimer interface), the mechanistic basis of homophilic cell-cell adhesion. Independently supported in this file by HDA evidence on the same term (PMID:25468996, the E-cadherin interactome) and the crystallographic reference PMID:21300292.

Reason: Core CDH1 molecular function — homophilic cadherin-cadherin binding via the ectodomain is the adhesive activity of E-cadherin. Corroborated by HDA evidence on this exact term (PMID:25468996) elsewhere in the file.

Summary: The inherited proposal captures the p120-catenin association of the E-cadherin juxtamembrane region.

Reason: This proposal was already present in the baseline and is preserved, not newly manufactured by this audit. PMID:15240885 Figure 5B shows E-cadherin/p120 co-immunoprecipitation in transfected L cells, with G-alpha12 increasing association. Human source-linked p120 records in PMID:19604117, PMID:33961781 and PMID:34591612 independently corroborate the partner class. GO:0070097 defines binding to the delta subunit of the catenin complex; it is used here for CTNND1/p120, without claiming that the L-cell experiment by itself resolves every construct species or a purified interface. The new generic-row refinements now also capture this class.

Summary: IBA projection from the PANTHER classical cadherin tree (PTHR24027) via GO_REF:0000033. E-cadherin is the founding component that organizes the epithelial adherens junction — clustering of trans-engaged cadherins together with recruitment of the catenin-actin module assembles and maintains the zonula adherens. Independently supported in this file by IMP evidence on the same term (PMID:21724833).

Reason: Core CDH1 biological process — E-cadherin organizes the adherens junction. Corroborated by IMP evidence on this exact term (PMID:21724833) elsewhere in the file.

Summary: IBA projection (is_active_in) from the PANTHER classical cadherin tree (PTHR24027) via GO_REF:0000033. The adherens junction (zonula adherens) is the principal site of E-cadherin residence and function in epithelial cells. This is a core CDH1 cellular component, independently supported in this file by multiple IDA rows on the same term (PMID:22294297, PMID:18343367, PMID:27760340, PMID:24046456, PMID:20086044, PMID:16338932).

Reason: Core CDH1 cellular component — the adherens junction is the defining site of E-cadherin localization and activity, corroborated by numerous IDA rows on this exact term in the file.

Summary: IBA projection from the PANTHER cadherin tree (PTHR24027) via GO_REF:0000033, originating from the broad ancestral node PTN000616414. Classical cadherins contribute to synapse assembly and stabilization in the nervous system, and E-cadherin has documented roles at neuronal synapses; however, for the canonical epithelial CDH1 this is a tissue-specific, non-core context rather than a defining function. The core CDH1 role is epithelial cell-cell adhesion at adherens junctions.

Reason: Retain the PAINT ancestral functional inference as a non-core neuronal context. The target is a classical cadherin; a short donor list does not invalidate the node. The complete historical node placement was not reconstructed, and the rat cadherin-blockade abstract alone does not resolve every construct. No claim that this function belongs exclusively to CDH2 is warranted.

Summary: IBA projection from the PANTHER classical cadherin tree (PTHR24027) via GO_REF:0000033. E-cadherin adhesion is strictly calcium-dependent — Ca2+ ions bridge the linker regions between extracellular cadherin (EC) domains, rigidifying the ectodomain into the conformation competent for homophilic trans-binding. GO:0016339 (attachment of one cell to another via adhesion molecules that require calcium) precisely describes the core CDH1 adhesive process. Consistent with the IEA GO:0005509 (calcium ion binding) row in this file.

Reason: Core CDH1 biological process — calcium-dependent homophilic cell-cell adhesion is the defining activity of E-cadherin.

Summary: E-cadherin associates with flotillins in cholesterol-sensitive plasma-membrane complexes in human MCF-7 cells.

Reason: Full PMID:24046456 Results and Figures 1B and 7D show reciprocal E-cadherin/flotillin immunoprecipitation and cholesterol-sensitive association. The current GO:0016600 definition explicitly says "and may contain associated proteins"; it does not require every associated protein to be a permanent structural subunit. Preserve the original part_of qualifier. For the IBA row, this human evidence corroborates rather than replaces the ancestral inference.

Summary: IBA projection (is_active_in) from the PANTHER cadherin tree (PTHR24027) via GO_REF:0000033, from the broad ancestral node PTN000616414. The apical junction complex (GO:0043296) is the composite apical unit comprising the tight junction, the zonula adherens and desmosomes. E-cadherin is the core of the zonula adherens, one of the three constituents of the apical junction complex, so the annotation is not wrong; however, the precise and core CDH1 cellular component is the adherens junction itself (GO:0005912, ACCEPTed in this review), and the broader composite grouping is best treated as non-core.

Reason: Accurate but broader-than-precise CC grouping; the precise core localization is GO:0005912 adherens junction. E-cadherin resides specifically in the zonula adherens sub-compartment of the apical junction complex.

Summary: IEA from InterPro2GO (GO_REF:0000002): E-cadherin has five extracellular cadherin (EC) domains, each pair bridged by three Ca2+ ions at the domain linker regions. Ca2+ binding rigidifies the extracellular domain into a rod-like conformation required for homophilic trans-dimerisation and cell-cell adhesion. Calcium ion binding is therefore a core molecular activity of CDH1, corroborated by the IBA GO:0016339 (calcium-dependent cell-cell adhesion) ACCEPT in this file.

Reason: Core CDH1 molecular function — Ca2+ binding via the EC-domain linkers is an obligate step in homophilic cadherin adhesion.

Summary: Released E-cadherin ectodomain is found extracellularly after proteolytic shedding.

Reason: Retain extracellular localization on the basis of an actually released product, not merely the external orientation of a membrane-bound domain. Human gastric-cell supernatant proteomics and cleavage assays in PMID:34742300 provide independent corroboration; the original electronic source is preserved.

Summary: E-cadherin has intracellular trafficking pools as well as its principal junctional membrane pool.

Reason: GO:0005737 includes intracellular organelles. Endosomal transit and processing make this broad located_in assertion defensible; it is not rejected simply because E-cadherin is a transmembrane protein. More informative core locations remain the lateral plasma membrane and adherens junction.

Summary: IEA from UniProt-GOA (GO_REF:0000044): CDH1/E-cadherin undergoes clathrin-mediated endocytosis and is trafficked through early endosomes during junction remodelling and in response to growth factor signalling. Endosomal localisation is real but is a trafficking/turnover context rather than the site of CDH1 core adhesion and junction-organising function.

Reason: Real but non-core CC — endosomal localisation reflects CDH1 endocytic turnover/recycling rather than core adhesion function; primary sites of CDH1 activity are plasma membrane and adherens junction.

Summary: IEA from UniProt-GOA (GO_REF:0000044): CDH1 is glycosylated and processed in the Golgi apparatus as part of the secretory pathway before reaching the plasma membrane. Golgi localisation is real but represents a transient biosynthetic/processing compartment rather than a site of CDH1 function.

Reason: Real but non-core CC — Golgi is a transient biosynthetic/processing compartment for CDH1 maturation; core localisation and function are at the plasma membrane and adherens junction.

Summary: IEA from UniProt keyword mapping (GO_REF:0000120): The plasma membrane is the primary site of CDH1/E-cadherin localization and function. E-cadherin concentrates at the lateral/basolateral plasma membrane of epithelial cells, where it mediates homophilic trans-dimerisation and cell-cell adhesion. Consistent with experimental IDA and TAS evidence on the same term elsewhere in this file.

Reason: Core CDH1 cellular component — the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity.

Summary: IEA from UniProt-GOA (GO_REF:0000044): The adherens junction is the principal and defining site of CDH1/E-cadherin localization and function in epithelial cells. E-cadherin is the core transmembrane component of the cadherin-catenin complex at the adherens junction. Already ACCEPTed for the IBA annotation (GO_REF:0000033) in this file.

Reason: Core CDH1 cellular component — the adherens junction is the defining site of CDH1 localization and activity; consistent with IBA ACCEPT on this term elsewhere in the file.

Summary: IEA from InterPro2GO (GO_REF:0000002): Cell adhesion is the defining biological process of CDH1/E-cadherin. E-cadherin mediates calcium-dependent homophilic cell-cell adhesion between epithelial cells and is the founding member of the classical cadherin family.

Reason: Core CDH1 biological process — cell adhesion is the defining function of E-cadherin.

Summary: IEA from InterPro2GO (GO_REF:0000002): Homophilic cell-cell adhesion is the specific core mechanism of CDH1 — E-cadherin engages in calcium-dependent homophilic trans-dimerisation with E-cadherin on adjacent cells, forming the molecular basis of epithelial cell-cell adhesion.

Reason: Core CDH1 biological process — homophilic cell-cell adhesion via the ectodomain strand-swap mechanism is the defining activity of E-cadherin.

Summary: E-cadherin is a membrane protein, with its main adhesive activity at the cell surface.

Reason: The membrane term is broad but correct. Retain it as non-core while the existing plasma-membrane and junctional annotations carry the useful spatial detail; breadth alone does not make this a biological over-annotation.

Summary: IEA from HGNC (GO_REF:0000117): CDH1 localizes to cell junctions. However, GO:0030054 cell junction is a broad parent term; the more specific and informative CC annotation is GO:0005912 adherens junction (ACCEPTed in this file), which is the precise junction type where E-cadherin resides and functions.

Reason: Broad parent CC — CDH1 localises to cell junctions but the precise junction type is the adherens junction (GO:0005912, accepted elsewhere); the broad parent term adds no annotation value.

Summary: IEA from UniProt-GOA (GO_REF:0000044, the UniProtKB Subcellular Location keyword-to-GO mapping — not generic cadherin-family domain mapping): CDH1/E-cadherin localizes to desmosomes. UniProt P12830 curates "Cell junction, desmosome" as an experimentally-supported subcellular location (ECO:0000269|PubMed:25208567, PubMed:29999492, PubMed:33596089), and E-cadherin plays a role in the early stages of desmosome cell-cell junction formation by facilitating recruitment of DSG2 and DSP to desmosome plaques (PubMed:29999492). CDH1 is not itself a desmosomal cadherin (those are the desmogleins/desmocollins), but its desmosome localization and early-assembly role are genuine biology, not an over-annotation. This is peripheral to the core E-cadherin function at the adherens junction (GO:0005912, ACCEPTed in this file). Two IDA annotations on this term (PMID:33596089, PMID:29999492) and an IMP on GO:0002159 desmosome assembly (PMID:29999492) are PENDING for review in a later batch and should be reviewed consistently as KEEP_AS_NON_CORE.

Reason: GO_REF:0000044 propagates UniProt's curated, experimentally-supported "Cell junction, desmosome" subcellular location (ECO:0000269|PubMed:25208567/29999492/33596089) — it is not generic domain mapping, and the desmosome localization plus early-desmosome-assembly role are genuine but peripheral to the core adherens-junction function of E-cadherin. Corrects the prior MARK_AS_OVER_ANNOTATED decision after a UniProt fact-check (see issue #348). follow-up.

Summary: IEA from HGNC (GO_REF:0000117): CDH1 participates in cell junction assembly — E-cadherin nucleates adherens junction assembly and via the catenin complex templates subsequent tight junction assembly. GO:0034329 cell junction assembly is valid but is a broad parent of GO:0007043 cell-cell junction assembly (already ACCEPTed via IBA in this file).

Reason: Valid but broad parent BP — CDH1 participates in cell junction assembly but the precise term GO:0007043 cell-cell junction assembly is already ACCEPTed via IBA; broad parent adds no annotation value.

Summary: IEA from InterPro2GO (GO_REF:0000002): Cell-cell adhesion is the core biological process of CDH1/E-cadherin — the protein mediates calcium-dependent homophilic cell-cell adhesion between adjacent epithelial cells. Consistent with GO:0007155 cell adhesion (also ACCEPTed) and GO:0044331 cell-cell adhesion mediated by cadherin (ACCEPTed via IBA in this file).

Reason: Core CDH1 biological process — cell-cell adhesion is the defining function of E-cadherin; consistent with GO:0044331 (IBA ACCEPT) and GO:0007155 (IEA ACCEPT).

Summary: Human E-cadherin associates with FGFR1 and beta-catenin in source-linked co-immunoprecipitation records.

Reason: Both original GOA partners are retained in the evidence extraction. Propose the two supported partner classes at complex-association resolution, without claiming kinase activity by E-cadherin. Source-linked curated record identifiers: intact:EBI-1381427|imex:IM-19960-1, intact:EBI-1381432|imex:IM-19960-2, intact:EBI-1381454|imex:IM-19960-4. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json. FGFR1 is a receptor tyrosine kinase, supporting the narrower GO:0030971 partner class.

Proposed replacements: receptor tyrosine kinase binding beta-catenin binding

Summary: The human E-cadherin EC1 region binds the bacterial internalin InlA.

Reason: The exact record links P12830 and P0DJM0 in an X-ray study, with human residues 156–255 and Listeria InlA 36–496. Retain this pathogen receptor contact as non-core; no bacterial enzymatic activity is assigned to the host protein; its receptor role independently supports the existing host-response row. Source-linked curated record identifiers: intact:EBI-1035409|rcsb pdb:1O6S. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json.

Summary: Human E-cadherin associates with protein kinase D1.

Reason: Exact human Q15139 pair records include co-immunoprecipitation and kinase-assay context. Refine to kinase binding; the kinase catalysis belongs to PRKD1. Source-linked curated record identifiers: intact:EBI-1536800|imex:IM-19457-1, intact:EBI-1536833|imex:IM-19457-2, intact:EBI-1536841|imex:IM-19457-3, intact:EBI-1536861|imex:IM-19457-4. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json.

Proposed replacements: protein kinase binding

Summary: The E-cadherin cytoplasmic region associates with alpha- and beta-catenin.

Reason: Exact human source records use the E-cadherin 736–882 region and pull-down/surface-plasmon-resonance methods. Preserve complex-association limits for alpha-catenin; no direct alpha-catenin interface is inferred solely from a ternary complex. Source-linked curated record identifiers: intact:EBI-727492, intact:EBI-762404. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json.

Proposed replacements: alpha-catenin binding beta-catenin binding

Summary: E-cadherin pull-down studies track beta-catenin association during HGF/VHL perturbation in renal carcinoma cells.

Reason: Refine the demonstrated catenin-associated activity while retaining the original experimental source. This does not assign the perturbing protein's regulatory function to E-cadherin or establish a purified interface from co-complex evidence.

Proposed replacements: beta-catenin binding

Summary: Human E-cadherin and beta-catenin occur in the source-associated co-immunoprecipitation complex.

Reason: The exact P35222 pair supports the catenin-specific refinement; the screen or regulatory perturbation is not a new molecular activity of E-cadherin. Source-linked curated record identifiers: intact:EBI-1191199, intact:EBI-1191206. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json.

Proposed replacements: beta-catenin binding

Summary: E-cadherin associates with beta-catenin in the CagA perturbation study.

Reason: The actual human pair is present in two MINT co-immunoprecipitation records. Pathogen disruption of this complex does not negate the positive association. Source-linked curated record identifiers: intact:EBI-55022074|imex:IM-30078-3, intact:EBI-55022085|imex:IM-30078-7. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json.

Proposed replacements: beta-catenin binding

Summary: E-cadherin associates with the human protein phosphatase 1 catalytic subunit PPP1CA.

Reason: Source-linked P62136 records identify co-immunoprecipitation and antibody-array evidence. Refine to phosphatase binding at the reported association resolution, without assigning dephosphorylation to E-cadherin. Source-linked curated record identifiers: intact:EBI-1207018|imex:IM-18875-48, intact:EBI-1207450|imex:IM-18875-80. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json.

Proposed replacements: protein phosphatase binding

Summary: Human E-cadherin EC1 binding to InlA is studied by structural and thermodynamic experiments.

Reason: The original abstract directly identifies the human EC1/internalin interaction and its engineered affinity changes. Retain the bacterial receptor contact as non-core; this receptor role also supports the separately retained existing host-response annotation, without adding a new process row.

Summary: E-cadherin and EPLIN associate in the human DLD-1 cadherin-catenin complex.

Reason: The full primary Results and Figure 1A show endogenous co-immunoprecipitation from human DLD-1 cells. Figure 1B reconstitution establishes that EPLIN reaches the E-cadherin tail through alpha- and beta-catenin; purified EPLIN does not bind the isolated E-cadherin tail. Retain the demonstrated indirect complex association as non-core under the project instruction, without assigning EPLIN actin-binding activity to E-cadherin.

Summary: The primary abstract reports stabilization of the E-cadherin/beta-catenin complex by Smad7.

Reason: Refine the demonstrated catenin-associated activity while retaining the original experimental source. This does not assign the perturbing protein's regulatory function to E-cadherin or establish a purified interface from co-complex evidence.

Proposed replacements: beta-catenin binding

Summary: The human E-cadherin tail is associated with alpha- and beta-catenin in the EspB study.

Reason: MINT target records explicitly recover P12830 with P35221 and P35222 using a GST-tagged E-cadherin 732–882 region. The foreground bacterial protein in the abstract does not exclude the actual cadherin assay. Source-linked curated record identifiers: intact:EBI-8501008|mint:MINT-7010191|imex:IM-13826-1. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json.

Proposed replacements: alpha-catenin binding beta-catenin binding

Summary: E-cadherin participates in infection-associated complexes containing CagA, p120-catenin and MET.

Reason: All three exact GOA partners are represented by MINT records, including the H.pylori accession A0A0S2C3P2. Human p120/MET associations and bacterial CagA association have different biological scopes; retain the collapsed source row as non-core without claiming each pair is a purified binary interface. Source-linked curated record identifiers: intact:EBI-55025802|imex:IM-30087-1, intact:EBI-55025821|imex:IM-30087-5, intact:EBI-55025841|imex:IM-30087-11, intact:EBI-55025856|imex:IM-30087-15. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json.

Summary: Human E-cadherin associates with tensin 3.

Reason: Exact Q68CZ2 co-immunoprecipitation records support this association, including a phosphotyrosine context. No more specific molecular activity of E-cadherin follows from the partner name; retain non-core under the project instruction. Source-linked curated record identifiers: intact:EBI-2638406|imex:IM-13611-9, intact:EBI-2638414|imex:IM-13611-4. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json.

Summary: The Cdh1 in this source is the APC/C coactivator FZR1 rather than E-cadherin/CDH1.

Reason: The full Methods specify HA-Cdh1 Addgene 11596, whose depositor record identifies human FZR1 (GenBank AF083810). This is a construct-based citation-identity correction after reading the relevant full primary text, not an inference from the paper title. The original source tuple remains intact.

Summary: The Cdh1 in this source is the APC/C coactivator FZR1 rather than E-cadherin/CDH1.

Reason: Full Results/Figure 2E test the Cdh1 C-terminal IR peptide and Figure 4C tests its APC association; this is the APC/C coactivator, not a cadherin construct. This is a construct-based citation-identity correction after reading the relevant full primary text, not an inference from the paper title. The original source tuple remains intact. The original GOA partner is P30260 (CDC27); a current curated P12830–APC1 record is a separate observation, not that original partner tuple. Neither accession mapping overrides the primary construct identity.

Summary: The paper describes Src-dependent regulation of E-cadherin phosphorylation and turnover.

Reason: The accessible abstract does not resolve the exact Src/E-cadherin binding assay and no source-linked exact interaction record was recovered. Absence from that lookup is not evidence against binding. Preserve the IPI assertion pending the relevant primary assay.

Summary: Selected Results state that beta-catenin Y333F and wild type similarly associate with E-cadherin in the supplementary control experiments.

Reason: Refine the demonstrated catenin-associated activity while retaining the original experimental source. This does not assign the perturbing protein's regulatory function to E-cadherin or establish a purified interface from co-complex evidence.

Proposed replacements: beta-catenin binding

Summary: The primary abstract reports a CRYAB-associated complex containing endogenous E-cadherin and beta-catenin.

Reason: Refine the demonstrated catenin-associated activity while retaining the original experimental source. This does not assign the perturbing protein's regulatory function to E-cadherin or establish a purified interface from co-complex evidence.

Proposed replacements: beta-catenin binding

Summary: A phosphotyrosine-containing human E-cadherin region binds the mouse Hakai HYB domain.

Reason: Exact source records include human E-cadherin 749–761, phospho-Y754, and mouse Q9JIY2 fragments, with ITC/NMR/pull-down and disruptive mutant comparisons. Retain the positive association as non-core at the tested cross-species/fragment scope; no ubiquitination activity is assigned to E-cadherin. Source-linked curated record identifiers: intact:EBI-7644975|mint:MINT-8386059|imex:IM-18523-33, intact:EBI-7645250|mint:MINT-8386657|imex:IM-18523-36, intact:EBI-7645462|mint:MINT-8386956|imex:IM-18523-34, intact:EBI-7645611|mint:MINT-8385996|imex:IM-18523-1. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json.

Summary: E-cadherin occurs in a junctional complex containing alpha-catenin and the Rho exchange factor ECT2.

Reason: Full PMID:22750944 Results/Figure 5A in human MCF7 cells identify reciprocal immune complexes; ECT2 association depends on alpha-catenin/centralspindlin organization. Retain the source's heterogeneous complex association without assigning ECT2 nucleotide exchange or a direct pairwise interface to E-cadherin.

Summary: Human E-cadherin associates with the source-linked receptor tyrosine kinase partner(s).

Reason: The exact EGFR records use tandem affinity purification. Refine the partner class while preserving the resolution of that assay; neither direct purified contact nor kinase activation by E-cadherin is claimed. Source-linked curated record identifiers: intact:EBI-8770081|imex:IM-21413-2. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json. EGFR is a receptor tyrosine kinase, supporting the narrower GO:0030971 partner class.

Proposed replacements: receptor tyrosine kinase binding

Summary: E-cadherin is proximal to p120-catenin and beta-catenin in the reported human-cell assay.

Reason: The exact two partner records use proximity ligation. The catenin classes are supported, while PLA itself is not treated as proof of a purified binary interface or normal activity of every disease variant. Source-linked curated record identifiers: intact:EBI-9846876|imex:IM-23235-1, intact:EBI-9846885|imex:IM-23235-2. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json.

Proposed replacements: delta-catenin binding beta-catenin binding

Summary: Human E-cadherin associates with the source-linked receptor tyrosine kinase partner(s).

Reason: The exact EGFR records use the MaMTH ubiquitin-reconstitution reporter. Refine the partner class while preserving the resolution of that assay; neither direct purified contact nor kinase activation by E-cadherin is claimed. Source-linked curated record identifiers: intact:EBI-9689407|imex:IM-23090-102. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json. EGFR is a receptor tyrosine kinase, supporting the narrower GO:0030971 partner class.

Proposed replacements: receptor tyrosine kinase binding

Summary: Human E-cadherin associates with the source-linked receptor tyrosine kinase partner(s).

Reason: The exact EGFR and FGFR1 records use proximity ligation. Refine the partner class while preserving the resolution of that assay; neither direct purified contact nor kinase activation by E-cadherin is claimed. Source-linked curated record identifiers: intact:EBI-6592802|imex:IM-18707-284, intact:EBI-6592813|imex:IM-18707-285. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json. EGFR and FGFR1 are receptor tyrosine kinases, supporting the narrower GO:0030971 partner class.

Proposed replacements: receptor tyrosine kinase binding

Summary: The primary abstract reports an ASPP2/beta-catenin/E-cadherin ternary complex.

Reason: Refine the demonstrated catenin-associated activity while retaining the original experimental source. This does not assign the perturbing protein's regulatory function to E-cadherin or establish a purified interface from co-complex evidence.

Proposed replacements: beta-catenin binding

Summary: Human E-cadherin associates with the source-linked receptor tyrosine kinase partner(s).

Reason: The exact EGFR records use the MaMTH ubiquitin-reconstitution reporter. Refine the partner class while preserving the resolution of that assay; neither direct purified contact nor kinase activation by E-cadherin is claimed. Source-linked curated record identifiers: intact:EBI-25371054|imex:IM-26434-514. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json. EGFR is a receptor tyrosine kinase, supporting the narrower GO:0030971 partner class.

Proposed replacements: receptor tyrosine kinase binding

Summary: The fragment-interaction screen records 25 human E-cadherin partner accessions.

Reason: All 25 original GOA partners join positive MINT/IntAct source records, including all four isoform-qualified accessions. Fragment boundaries are retained in the extract. The heterogeneous partner set has no single justified narrower replacement; retain non-core. Repeated array, pooled and validation records are assay provenance, not independent biological replication. Source-linked curated record identifiers: intact:EBI-25836397|imex:IM-28217-28511, intact:EBI-25837285|imex:IM-28217-52431, intact:EBI-25837293|imex:IM-28217-40693, intact:EBI-25837301|imex:IM-28217-16737. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json.

Summary: BioPlex records E-cadherin associations with p120-catenin and beta-catenin.

Reason: Both exact human partners are supported by source-linked anti-tag AP-MS records. Refine the catenin classes at complex-association resolution; no direct binding interface or independent replication across repeated releases is claimed. Source-linked curated record identifiers: intact:EBI-54583800|imex:IM-29278-2471, intact:EBI-54736260|imex:IM-29278-9851, intact:EBI-54977153|imex:IM-29278-27081. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json.

Proposed replacements: delta-catenin binding beta-catenin binding

Summary: The breast-cancer interaction study records E-cadherin associations with three catenins.

Reason: Exact human MINT records support p120-, alpha- and beta-catenin associations. Some records carry a CDH1 position 243 mutation; the extraction retains that feature without inventing its substitution or generalizing the assay to all wild-type contexts. The supported catenin class remains informative. Source-linked curated record identifiers: intact:EBI-34580737|imex:IM-29535-143, intact:EBI-34580863|imex:IM-29535-183, intact:EBI-34580872|imex:IM-29535-161, intact:EBI-34581511|imex:IM-29535-91. Complete exact pair/taxon/method/feature extraction is in CDH1-interaction-evidence.json.

Proposed replacements: delta-catenin binding alpha-catenin binding beta-catenin binding

Summary: The official OpenCell AP-MS table contains a CTNNB1-bait/CDH1-prey association.

Reason: The CDH1 prey is a protein group that includes P12830 and P12830-2; this does not resolve an individual CDH1 isoform or a direct interface. Refine to beta-catenin binding at complex-association resolution. The source dataset row, retrieval provenance and protein-group identifiers are preserved in the interaction extract.

Proposed replacements: beta-catenin binding

Summary: E-cadherin homophilic association is a core molecular feature of its adhesive function.

Reason: PMID:19114658 uses single-molecule FRET and force measurements to distinguish trans association from a proposed cis-dimer intermediate; it does not support a blanket disulfide-dimer statement. Homophilic association is a core E-cadherin activity independently supported by PMID:21300292. The original assertion and provenance remain intact.

Summary: E-cadherin homophilic association is a core molecular feature of its adhesive function.

Reason: PMID:19646884 uses W2A ectodomain constructs and single-molecule measurements to analyze a weak encounter complex preceding strand swapping; the human IgG Fc label is not proof of a human cadherin construct. Homophilic association is a core E-cadherin activity independently supported by PMID:21300292. The original assertion and provenance remain intact.

Summary: E-cadherin homophilic association is a core molecular feature of its adhesive function.

Reason: PMID:21300292 combines mouse ectodomain structures with full-length human E-cadherin junctional mutants; those experimental arms are distinguished. Homophilic association is a core E-cadherin activity independently supported by PMID:21300292. The original assertion and provenance remain intact.

Summary: E-cadherin homophilic association is a core molecular feature of its adhesive function.

Reason: The PMID:23112161 abstract explicitly describes E-cadherin catch, slip and ideal adhesive bonds, but the full construct methods were not newly inspected. Homophilic association is a core E-cadherin activity independently supported by PMID:21300292. The original assertion and provenance remain intact.

Summary: E-cadherin homophilic association is a core molecular feature of its adhesive function.

Reason: Full PMID:24725409 Results/Figure 4 use E-cadherin ectodomain-coated beads as a positive homophilic aggregation control, despite the paper foregrounding protocadherins. Homophilic association is a core E-cadherin activity independently supported by PMID:21300292. The original assertion and provenance remain intact.

Summary: E-cadherin homophilic association is a core molecular feature of its adhesive function.

Reason: The exact PMID:35922511 supplementary homophilic pair was not independently joined. Retention is supported by independent primary human E-cadherin function/structure evidence, not a claim that the screen table was read. Homophilic association is a core E-cadherin activity independently supported by PMID:21300292. The original assertion and provenance remain intact.

Summary: The electronic synapse-assembly assertion has a rat E-cadherin orthology donor.

Reason: Retain this in the same non-core neuronal context as the PAINT assertion. The current donor is rat E-cadherin Q9R0T4, not N-cadherin; PMID:12123610 reports cadherin blockade during hippocampal synaptogenesis, but its abstract does not resolve every construct identity. This is not independent human experimental evidence, and no target-specific loss of the inherited activity was established.

Summary: IEA from UniProt keyword mapping (GO_REF:0000120): Beta-catenin binding by the CDH1 cytoplasmic tail is the canonical molecular mechanism of the cadherin-catenin complex. The E-cadherin cytoplasmic domain directly binds beta-catenin (CTNNB1); this interaction links the cadherin to the actin cytoskeleton via alpha-catenin and is the basis of the adherens junction. Already ACCEPTed for the IBA annotation in this file.

Reason: Core CDH1 molecular function — beta-catenin binding by the cytoplasmic domain is the canonical interaction of the cadherin-catenin complex; consistent with IBA ACCEPT on this term.

Summary: Rat gingival E-cadherin expression and membrane staining decrease after cyclosporin A exposure.

Reason: The traced rat E-cadherin source measures expression or localization changes after the stimulus. That establishes a responsive readout, but the inspected evidence does not show E-cadherin performing a step in the stimulus-response mechanism. The electronic process transfer therefore exceeds the established participation evidence; the original donor/source fields remain intact. This does not dispute the reported staining/expression change or imply a different cadherin was assayed.

Summary: Rat prostatic E-cadherin expression and localization change after prenatal tributyltin exposure.

Reason: The traced rat E-cadherin source measures expression or localization changes after the stimulus. That establishes a responsive readout, but the inspected evidence does not show E-cadherin performing a step in the stimulus-response mechanism. The electronic process transfer therefore exceeds the established participation evidence; the original donor/source fields remain intact. This does not dispute the reported staining/expression change or imply a different cadherin was assayed.

Summary: The rat donor study maps E- and N-cadherin expression during pituitary histogenesis.

Reason: PMID:17373711 explicitly assays rat E-cadherin, so the previous paralog speculation is unwarranted. Expression during development alone does not establish that E-cadherin performs a step in pituitary development; retain the over-annotation judgment on this evidential distinction, not merely because the process is tissue-specific.

Summary: The axon-growth donor experiment concerns the Cdh1-APC ubiquitin-ligase regulator FZR1.

Reason: The actual rat donor Q9R0T4 points to PMID:23226367. Full Results/Figures 1–3 and Plasmids and Reagents describe HA/GFP-Cdh1 in the APC/Smurf1/p250GAP pathway and Cdh1 RNAi in rat granule neurons. This is a source-identity error in the propagated chain, not a transfer from an unspecified neural cadherin. The exact RNAi target and plasmid sequences were not independently authenticated; the conclusion uses the full APC-coactivator experimental context, not a WD40 experiment claimed for this paper.

Summary: The rat donor study measures E-cadherin redistribution during lesion-associated axonal sprouting.

Reason: PMID:12387456 distinguishes E-cadherin from N-cadherin and documents their different expression patterns. That temporal expression correlation is insufficient to establish participation in neuron projection development. This is not an argument that E-cadherin cannot occur in the nervous system.

Summary: Heparin and enoxaparin alter E-cadherin staining in rat placental/decidual tissues.

Reason: The traced rat E-cadherin source measures expression or localization changes after the stimulus. That establishes a responsive readout, but the inspected evidence does not show E-cadherin performing a step in the stimulus-response mechanism. The electronic process transfer therefore exceeds the established participation evidence; the original donor/source fields remain intact. This does not dispute the reported staining/expression change or imply a different cadherin was assayed. PubMed also lists a 2023 correction whose full text was not recovered; no assumption about its content or a retraction is made.

Summary: The synaptic donor evidence assays APC/C coactivator Cdh1/FZR1 rather than E-cadherin.

Reason: The live rat Q9R0T4 donor record cites PMID:21186356. The full author-hosted article, Results/Figures 6–7 and online Methods, tests a Cdh1 deletion of the WD40 substrate-binding domain, APC-dependent GluR1 ubiquitination and neuronal knockdown/rescue. This construct identity contradicts transfer to E-cadherin. It does not establish that E-cadherin has no neuronal functions.

Summary: The synaptic donor evidence assays APC/C coactivator Cdh1/FZR1 rather than E-cadherin.

Reason: The live rat Q9R0T4 donor record cites PMID:21186356. The full author-hosted article, Results/Figures 6–7 and online Methods, tests a Cdh1 deletion of the WD40 substrate-binding domain, APC-dependent GluR1 ubiquitination and neuronal knockdown/rescue. This construct identity contradicts transfer to E-cadherin. It does not establish that E-cadherin has no neuronal functions.

Summary: The synaptic donor evidence assays APC/C coactivator Cdh1/FZR1 rather than E-cadherin.

Reason: The live rat Q9R0T4 donor record cites PMID:21186356. The full author-hosted article, Results/Figures 6–7 and online Methods, tests a Cdh1 deletion of the WD40 substrate-binding domain, APC-dependent GluR1 ubiquitination and neuronal knockdown/rescue. This construct identity contradicts transfer to E-cadherin. It does not establish that E-cadherin has no neuronal functions.

Summary: E-cadherin participates in the cellular response to Gram-positive Listeria as the host receptor for InlA; this is independent of the rat Bifidobacterium donor.

Reason: The rat E-cadherin donor PMID:20501441 measures expression/localization after Bifidobacterium treatment and alone does not establish mechanistic participation. Independently, human E-cadherin binds Listeria monocytogenes InlA through EC1 and acts as the receptor used for host-cell entry (PMID:12526809 and PMID:17715295; Reactome:R-HSA-8876497 and subsequent CDH1-complex events). This receptor engagement supplies a host molecular step in the response, rather than merely an expression readout. Retain the existing broad response term as non-core on that separate support. The original electronic donor/source fields are unchanged; the Listeria evidence does not repair the Bifidobacterium provenance or establish an immune-defense activity. PMID:10963665 directly compares human E-cadherin constructs in L2071 fibroblasts: cytoplasmic/catenin-binding deletion impairs uptake while attachment remains, and a human E-cadherin/mouse alpha-catenin chimera restores uptake of internalin-coated beads. Caco-2/LoVo experiments support recruitment in human epithelial cells. This experimentally separates receptor coupling from passive binding.

Summary: Human E-cadherin association with receptor tyrosine kinases is supported independently of the electronic donor.

Reason: The rat donor PMID:12700184 explicitly reports Fer association with N-cadherin but not E-cadherin, so that donor source is problematic. Independent human FGFR1/EGFR association records in PMID:11401320, PMID:24658140 and PMID:25241761 support the biological term. Preserve the original electronic tuple and distinguish this independent support from repair of its provenance.

Summary: Proteolytic shedding releases E-cadherin material into human gastric-cell supernatants.

Reason: Full PMID:34742300 Table 1 and Results detect E-cadherin peptides enriched after H.pylori HtrA treatment of MKN28 cells. Retain the extracellular located_in assertion for the released product, not merely the membrane ectodomain.

Summary: IDA from PMID:36309486 (Myo Min KK et al. 2022): E-cadherin plasma membrane localization confirmed in islet/epithelial context. Plasma membrane is the canonical and core localization for functional E-cadherin mediating cell-cell adhesion.

Summary: Independent primary imaging places E-cadherin at nascent human desmosomal contacts.

Reason: PMID:29999492 uses structured-illumination imaging in primary human keratinocytes and distinguishes early E-cadherin enrichment from later desmosome maturation. Retain the biological location as non-core on this independent support. The exact desmosomal CDH1 observation underlying the original PMID:33596089 assignment was not separately resolved; its source tuple is preserved rather than silently reassigned.

Summary: IDA from GO_REF:0000052 (UniProtKB keyword-to-GO mapping): E-cadherin transits through the Golgi apparatus during biosynthesis and post-translational N-glycosylation (critical for correct E-cadherin folding and function). Golgi localization is a real but non-core CC reflecting biosynthetic/trafficking transit.

Reason: Golgi localization is part of the E-cadherin biosynthetic pathway, not its core adhesive function site. Core CC is plasma membrane/adherens junction.

Summary: IDA from GO_REF:0000052 (UniProtKB keyword-to-GO mapping): Plasma membrane localization is the canonical site for functional E-cadherin. E-cadherin is a type-I transmembrane protein whose extracellular cadherin domains mediate homophilic trans-adhesion at the plasma membrane — unambiguously core CC.

Summary: IDA from GO_REF:0000052 (UniProtKB keyword-to-GO mapping): E-cadherin is the canonical adhesion receptor at cell-cell junctions. GO:0030054 cell junction is the broad parent of GO:0005912 adherens junction; it is a valid CC annotation but the precise core localization is the adherens junction, ACCEPTed elsewhere in this file.

Reason: Broad parent CC — GO:0030054 cell junction is a broader category than GO:0005912 adherens junction, the precise core CC for E-cadherin (ACCEPTed in this file). A real but non-core annotation: the informative term is the specific adherens junction. Action reconciled with the IEA and TAS GO:0030054 rows in this file.

Summary: EXP from PMID:15689490 (Lock and Stow 2005): Rab11-positive recycling endosomes are an intermediate compartment for post-Golgi trafficking and exocytic delivery of E-cadherin to the basolateral plasma membrane. Endosomal localization is real and functionally important for E-cadherin surface delivery, but represents trafficking transit rather than the core functional site.

Reason: E-cadherin transits through recycling endosomes during biosynthetic delivery to the basolateral membrane — a real but non-core CC. Core localization is at the plasma membrane/adherens junction.

Summary: EXP from PMID:19403558 (Pinho et al. 2009): GnT-III knockdown causes membrane de-localization of E-cadherin leading to cytoplasmic accumulation, confirming that plasma membrane is the normal core localization of E-cadherin. Wild-type E-cadherin is robustly present at the plasma membrane.

Summary: E-cadherin binding to cadherin on another cell mediates cell-cell adhesion; refined to cell-cell adhesion mediator activity.

Reason: Correct but general: PMID:11976333 directly tests E-cadherin-dependent cell aggregation and its inhibition by G-alpha12/13, so the mediator activity is specifically cell-cell adhesion mediator activity (GO:0098632), an is_a child of GO:0098631. An earlier pass proposed the precomposed GO:0098641 cadherin binding involved in cell-cell adhesion; per projects/INVOLVED_IN_PRECOMPOSITION.md its cadherin-binding half is already carried by this review's GO:0045296 rows (IBA, HDA) and its core function, so this row keeps the mediator claim within its own branch rather than moving to cadherin binding. The original source term is preserved, and no activity of the G protein is transferred to E-cadherin.

Proposed replacements: cell-cell adhesion mediator activity

Summary: TAS from Reactome (R-HSA-9935547): Endocytosed, ubiquitinated CDH1/E-cadherin is sorted to lysosomes for degradation as part of junction turnover and downregulation. Lysosomal localization is real but reflects CDH1 degradative turnover rather than the site of its core adhesion function.

Reason: Real but non-core CC -- lysosomal localization reflects CDH1 degradative turnover; core localization and function are at the plasma membrane and adherens junction.

Summary: TAS from Reactome (R-HSA-9935552): Endocytosed, ubiquitinated CDH1/E-cadherin is sorted to lysosomes for degradation as part of junction turnover and downregulation. Lysosomal localization is real but reflects CDH1 degradative turnover rather than the site of its core adhesion function.

Reason: Real but non-core CC -- lysosomal localization reflects CDH1 degradative turnover; core localization and function are at the plasma membrane and adherens junction.

Summary: TAS from Reactome (R-HSA-9934752): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-9934753): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-9934752): CDH1/E-cadherin undergoes clathrin-mediated endocytosis and is trafficked through early endosomes during junction remodelling, recycling, and degradative sorting (e.g. following CBLL1/Hakai-mediated ubiquitination). Early endosome localization is real but reflects CDH1 trafficking/turnover rather than the site of its core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA endosome annotation in this file.

Reason: Real but non-core CC -- early endosome localization reflects CDH1 endocytic trafficking/turnover; consistent with KEEP_AS_NON_CORE on the IEA endosome row.

Summary: TAS from Reactome (R-HSA-9935552): CDH1/E-cadherin undergoes clathrin-mediated endocytosis and is trafficked through early endosomes during junction remodelling, recycling, and degradative sorting (e.g. following CBLL1/Hakai-mediated ubiquitination). Early endosome localization is real but reflects CDH1 trafficking/turnover rather than the site of its core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA endosome annotation in this file.

Reason: Real but non-core CC -- early endosome localization reflects CDH1 endocytic trafficking/turnover; consistent with KEEP_AS_NON_CORE on the IEA endosome row.

Summary: TAS from Reactome (R-HSA-9934751): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-9934755): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-9766227): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-9934584): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-9766223): CDH1/E-cadherin undergoes clathrin-mediated endocytosis and is trafficked through early endosomes during junction remodelling, recycling, and degradative sorting (e.g. following CBLL1/Hakai-mediated ubiquitination). Early endosome localization is real but reflects CDH1 trafficking/turnover rather than the site of its core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA endosome annotation in this file.

Reason: Real but non-core CC -- early endosome localization reflects CDH1 endocytic trafficking/turnover; consistent with KEEP_AS_NON_CORE on the IEA endosome row.

Summary: TAS from Reactome (R-HSA-9934584): CDH1/E-cadherin undergoes clathrin-mediated endocytosis and is trafficked through early endosomes during junction remodelling, recycling, and degradative sorting (e.g. following CBLL1/Hakai-mediated ubiquitination). Early endosome localization is real but reflects CDH1 trafficking/turnover rather than the site of its core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA endosome annotation in this file.

Reason: Real but non-core CC -- early endosome localization reflects CDH1 endocytic trafficking/turnover; consistent with KEEP_AS_NON_CORE on the IEA endosome row.

Summary: TAS from Reactome (R-HSA-9766219): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-9816278): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-9817325): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-9817330): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-9934294): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-9934410): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-9934411): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-9934486): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-9816275): CDH1/E-cadherin transits and is further processed/glycosylated in the Golgi apparatus en route from the ER to the plasma membrane. Golgi localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.

Reason: Real but non-core CC -- the Golgi is a transient biosynthetic/processing compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus row.

Summary: TAS from Reactome (R-HSA-9816278): CDH1/E-cadherin transits and is further processed/glycosylated in the Golgi apparatus en route from the ER to the plasma membrane. Golgi localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.

Reason: Real but non-core CC -- the Golgi is a transient biosynthetic/processing compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus row.

Summary: TAS from Reactome (R-HSA-9934330): CDH1/E-cadherin transits and is further processed/glycosylated in the Golgi apparatus en route from the ER to the plasma membrane. Golgi localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.

Reason: Real but non-core CC -- the Golgi is a transient biosynthetic/processing compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus row.

Summary: TAS from Reactome (R-HSA-9935209): CDH1/E-cadherin transits and is further processed/glycosylated in the Golgi apparatus en route from the ER to the plasma membrane. Golgi localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.

Reason: Real but non-core CC -- the Golgi is a transient biosynthetic/processing compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus row.

Summary: TAS from Reactome (R-HSA-9816275): CDH1/E-cadherin transits and is further processed/glycosylated in the Golgi apparatus en route from the ER to the plasma membrane. Golgi localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.

Reason: Real but non-core CC -- the Golgi is a transient biosynthetic/processing compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus row.

Summary: TAS from Reactome (R-HSA-9816273): CDH1/E-cadherin transits and is further processed/glycosylated in the Golgi apparatus en route from the ER to the plasma membrane. Golgi localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.

Reason: Real but non-core CC -- the Golgi is a transient biosynthetic/processing compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus row.

Summary: TAS from Reactome (R-HSA-9816273): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.

Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction.

Summary: TAS from Reactome (R-HSA-9933194): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.

Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction.

Summary: TAS from Reactome (R-HSA-9933380): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.

Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction.

Summary: TAS from Reactome (R-HSA-9816277): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.

Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction.

Summary: TAS from Reactome (R-HSA-9932352): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.

Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction.

Summary: TAS from Reactome (R-HSA-9932913): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.

Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction.

Summary: TAS from Reactome (R-HSA-9932988): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.

Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction.

Summary: TAS from Reactome (R-HSA-9816276): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.

Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction.

Summary: TAS from Reactome (R-HSA-9932344): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.

Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction.

Summary: TAS from Reactome (R-HSA-9932162): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.

Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction.

Summary: TAS from Reactome (R-HSA-9932162): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.

Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction.

Summary: IMP from PMID:29999492 (Shafraz et al. 2018): E-cadherin cis-dimerization site (Leu-175) is required for efficient desmoglein-2 (Dsg2) recruitment and desmosome assembly in keratinocytes. E-cadherin facilitates desmosome assembly by initially recruiting Dsg2 via a direct Ca2+-independent heterophilic interaction, with Ecad levels in desmosomes decreasing as junctions mature.

Reason: E-cadherin's role in desmosome assembly is real but non-core — it facilitates early desmosomal junction initiation as an auxiliary function. E-cadherin's primary role is adherens junction formation and homophilic cadherin-mediated cell-cell adhesion. The L175D mutant experiments use mouse E-cadherin constructs; the separate localization arm uses primary human keratinocytes. Do not describe the mutant arm as direct human-protein evidence.

Summary: IDA from PMID:29999492 (Shafraz et al. 2018): Super-resolution imaging shows E-cadherin is enriched in nascent desmosomes (1 hr after Ca2+ switch), declining 50% as desmosomes mature by 18 hr. E-cadherin transiently localizes to nascent desmosomal sites where it recruits Dsg2, but is displaced from mature desmosomes.

Reason: Desmosomal localization is transient and non-core for E-cadherin — it functions to nucleate early junction formation but is not a permanent resident of mature desmosomes (desmoglein/desmocollin are the stable components). Core CC is plasma membrane/adherens junction.

Summary: E-cadherin promotes recruitment of desmoglein 2 and desmoplakin to nascent cell contacts.

Reason: PMID:29999492 directly tests the Ecad cis-interface mutant L175 in junction recruitment. The broad positive protein-localization term is correct but non-core; breadth and overlap with desmosome assembly do not by themselves make it biologically wrong. The L175D mutant experiments use mouse E-cadherin constructs; the separate localization arm uses primary human keratinocytes. Do not describe the mutant arm as direct human-protein evidence.

Summary: IPI from PMID:18593713 (Tang et al. 2008): Smad7 stabilizes the beta-catenin-E-cadherin complex at the plasma membrane. E-cadherin physically binds beta-catenin through its cytoplasmic tail — this is the canonical CDH1-CTNNB1 armadillo repeat interaction that links E-cadherin to the actin cytoskeleton via alpha-catenin. Beta-catenin binding is core MF for E-cadherin.

Summary: IDA from PMID:18593713 (Tang et al. 2008): Smad7 promotes cell-cell adhesion by increasing the beta-catenin-E-cadherin complex level at the plasma membrane. Cell-cell adhesion mediated by cadherin is the defining core BP for E-cadherin, confirmed in this study through perturbation of the cadherin complex.

Summary: The primary abstract reports association of nonjunctional desmoglein 3 with E-cadherin.

Reason: Retain the experimentally reported cadherin complex association as non-core at the abstract-supported scope. No purified direct interface or desmoglein activity is transferred to E-cadherin.

Summary: E-cadherin has intracellular as well as junctional pools.

Reason: Retain the broad cytoplasmic location at the original experimental resolution, corroborated independently by intracellular trafficking evidence. A transmembrane topology does not exclude localization in intracellular organelles. The exact source figure in PMID:22294297 was not newly inspected.

Summary: IDA from PMID:22294297 (Tsang et al. 2012): Non-junctional Dsg3 regulates Src and E-cadherin adherens junction formation. Adherens junction is the core CC for functional E-cadherin — E-cadherin organizes with beta-catenin, alpha-catenin, and p120-catenin at adherens junctions to mediate epithelial cell-cell adhesion.

Summary: IDA from PMID:18343367: Adherens junction localization of E-cadherin confirmed experimentally. Core CC for E-cadherin — adherens junctions are the primary site of E-cadherin-mediated cell-cell adhesion in epithelial cells.

Summary: IDA from PMID:20859650: Plasma membrane localization of E-cadherin confirmed. Core CC — E-cadherin is a type-I transmembrane protein that localizes to the basolateral plasma membrane of epithelial cells where it mediates homophilic adhesion.

Summary: IDA from PMID:27760340: Adherens junction localization confirmed experimentally. Core CC for E-cadherin.

Summary: TAS from Reactome (R-HSA-9768614): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.

Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction.

Summary: TAS from Reactome (R-HSA-9768618): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.

Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction.

Summary: Plakophilin2 and beta-catenin affect E-cadherin complex organization.

Reason: The accessible abstract establishes PKP2/beta-catenin binding and competition with E-cadherin, but the exact assays supporting both original GOA partner pairs were not inspected. Preserve uncertainty for the collapsed source row; do not equate competition with a positive direct PKP2/E-cadherin interaction.

Summary: ARVCF binds the E-cadherin juxtamembrane region and competes with p120-catenin.

Reason: The accessible primary abstract supports a catenin-associated interaction network. Retain the collapsed ARVCF/p120/beta-catenin source row as non-core without treating all three as the same purified interface or inventing a modern isoform distinction.

Summary: IMP from PMID:21724833 (Lin et al. 2011): PTPN23 knockdown increases E-cadherin internalization and impairs adherens junction integrity, identifying E-cadherin as a key regulator/component of adherens junction organization. E-cadherin is the core structural component whose proper trafficking and membrane retention is essential for adherens junction maintenance.

Summary: Endogenous SPEF1/CLAMP associates with E-cadherin in human intestinal epithelial cells.

Reason: Selected full PMID:31473225 Results/Figures 4C,E,F describe PLA and reciprocal immunoprecipitation in SKCO-15 cells. The association is retained without assigning CLAMP actin-binding or microtubule-related activity to E-cadherin.

Summary: E-cadherin-mediated contacts affect MGAT3 expression in the original cell model.

Reason: The source abstract reports a reciprocal relationship between E-cadherin-dependent adhesion and glycosylation-related gene expression. Retain this context-dependent regulation as non-core; a broad process term is not false merely because only one regulated target was assayed.

Summary: E-cadherin-dependent adhesion can restrain cell migration.

Reason: The original PMID:16882694 abstract links weakened E-cadherin adhesion to faster directional wound closure after AF6i3 depletion. Independent PMID:11976333 directly reports migration inhibition after ectopic E-cadherin expression. Retain the context-dependent regulatory process as non-core, separating these different perturbations.

Summary: HDA from PMID:25468996 (Guo et al. 2014): E-cadherin interactome quantitative proteomics using proximity biotinylation (BioID). Cadherin binding is confirmed — E-cadherin mediates homophilic trans-adhesion by binding to E-cadherin on opposing cells (strand-swap dimer) and to other cadherin family members. Cadherin binding is core MF for E-cadherin.

Reason: The original HDA source is an E-cadherin proximity interactome; proximity labeling is not itself proof of a purified cadherin interface. Retain the established core cadherin-binding activity on independent primary structure/function evidence from PMID:21300292 while preserving the source attribution.

Summary: IDA from PMID:16338932 (Peignon et al. 2006): E-cadherin-dependent cell-cell adhesion controls nuclear abundance of HNF4alpha in Caco-2 enterocytes, linking E-cadherin engagement to increased nuclear import of this transcription factor. This is an indirect downstream signaling consequence of E-cadherin adhesion, not a direct E-cadherin MF.

Reason: Positive regulation of protein import into nucleus is an indirect consequence of E-cadherin-mediated adhesion signaling (via HNF4alpha redistribution), not a core CDH1 function. E-cadherin's primary role is cell-cell adhesion at adherens junctions.

Summary: IDA from PMID:28301459: Plasma membrane localization of E-cadherin confirmed experimentally. Core CC.

Summary: IDA from PMID:28169360: Cell junction localization of E-cadherin confirmed experimentally. GO:0030054 cell junction is the broad parent of GO:0005912 adherens junction; the precise core CC is the adherens junction, ACCEPTed elsewhere in this file.

Reason: Broad parent CC — GO:0030054 cell junction is a broader category than GO:0005912 adherens junction, the precise core CC for E-cadherin (ACCEPTed in this file). A real but non-core annotation: the informative term is the specific adherens junction. Action reconciled with the IEA and TAS GO:0030054 rows in this file.

Summary: TAS from Reactome (R-HSA-8876948): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-8876993): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-8877003): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: IDA from PMID:24046456 (Guillaume et al. 2013): Flotillins stabilize E-cadherin at cell-cell junctions; flotillin and E-cadherin complexes co-localize at CCJs. Adherens junction is confirmed as core CC for E-cadherin.

Summary: E-cadherin associates with flotillins in cholesterol-sensitive plasma-membrane complexes in human MCF-7 cells.

Reason: Full PMID:24046456 Results and Figures 1B and 7D show reciprocal E-cadherin/flotillin immunoprecipitation and cholesterol-sensitive association. The current GO:0016600 definition explicitly says "and may contain associated proteins"; it does not require every associated protein to be a permanent structural subunit. Preserve the original part_of qualifier. This IDA is supported by the human immunoprecipitation experiments at complex-association resolution.

Summary: Endogenous E-cadherin colocalizes with flotillin 2 in human MCF7 lamellipodia.

Reason: The full primary Figure 2E legend explicitly identifies the E-cadherin signal and lamellipodial arrows. This resolves the previous abstract-only doubt; retain the original located_in assertion as a non-core motile-cell location.

Summary: E-cadherin/catenin/flotillin junctional signals colocalize with cortical F-actin.

Reason: Full PMID:24046456 Figure 3B uses human MCF7 staining and structured-illumination microscopy. Preserve the original colocalizes_with qualifier: this is not a claim that E-cadherin itself binds purified actin.

Summary: Phosphorylated E-cadherin is captured by the PTPN23 E1357A substrate-trapping domain.

Reason: Full PMID:21724833 Results associated with supplementary Figure 13A identify E-cadherin in the mutant-domain pull-down from pervanadate-treated human-cell lysate. PTPN23 is not established here as a cell-adhesion-molecule ligand. Its disputed catalytic competence and the trapping-mutant context do not justify a phosphatase-binding class refinement; generalize to supported non-core protein association, without claiming E-cadherin catalytic activity. The original cell-adhesion-molecule partner class is unsupported because the demonstrated partner is PTPN23. GO:0005515 is a deliberate specificity downgrade to a non-core association under the explicit campaign supported-binding instruction, not a proposed new core function.

Proposed replacements: protein binding

Summary: The exact E-cadherin entry in the prostatic-secretions exosome proteomics table remains uninspected.

Reason: The full primary article and its supplemental Table S2 identity were recovered, but target-table retrievals returned challenge/error content rather than the data. The original HDA localization assertion is preserved as undecided. The main article alone does not establish the CDH1 protein entry, vesicle localization of a particular isoform, passive shedding, or release of an ectodomain fragment.

Summary: The recovered CD46 supplementary experiment identifies alpha-E-catenin, while the precise source of the CDH1/CD46 assertion remains unresolved.

Reason: The genuine PMID:23086448 supplementary PDF Figure 4a and legend were independently inspected: CD46 immunoprecipitation and alpha-E-catenin detection use primary human CD4 T cells, with CD3/isotype and gamma-secretase-inhibitor controls. Main Methods identify alpha-E-catenin antibody and siRNA reagents. The original GOA tuple explicitly links P12830 to P15529, but its curation-to-assay linkage was not recovered; that figure alone is insufficient to assert a whole-paper misattribution. Preserve the exact experimental assertion as undecided.

Summary: E-cadherin helps recruit plakophilin 3 and other desmosomal proteins to cell borders.

Reason: Full PMID:20859650 Figure 6 tests E-cadherin depletion in human HCT116 cells: PKP3, PKP2 and desmoplakin decrease at borders, whereas plakoglobin is not similarly depleted. Low-calcium complex/localization assays support a junctional recruiting role. Retain this non-core protein-localization process because E-cadherin helps organize the destination, not merely because E-cadherin itself is transported.

Summary: Released E-cadherin ectodomain occurs in the extracellular compartment.

Reason: Retain the Reactome extracellular assertion for a released protein product, supported independently by the human gastric-cell shedding experiments in PMID:34742300. It is non-core relative to the membrane-anchored adhesive activity; external orientation of an attached domain alone is not the rationale.

Summary: Released E-cadherin ectodomain occurs in the extracellular compartment.

Reason: Retain the Reactome extracellular assertion for a released protein product, supported independently by the human gastric-cell shedding experiments in PMID:34742300. It is non-core relative to the membrane-anchored adhesive activity; external orientation of an attached domain alone is not the rationale.

Summary: TAS from Reactome (R-HSA-3827958): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-4224014): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-NUL-2534209): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-202939): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-265422): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-419001): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-419002): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-5672304): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-8876497): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-9825774): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: TAS from Reactome (R-HSA-9926527): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.

Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file.

Summary: The abstract reports that anti-CDH1 antibody precipitates beta-catenin from human cumulus-cell extracts.

Reason: Refine the demonstrated catenin-associated activity while retaining the original experimental source. This does not assign the perturbing protein's regulatory function to E-cadherin or establish a purified interface from co-complex evidence.

Proposed replacements: beta-catenin binding

Summary: IMP from PMID:17620337 (Kizhatil et al. 2007): Ankyrin-G and beta-2-spectrin are required for exit of E-cadherin from the trans-Golgi network in a microtubule-dependent pathway. TGN is the staging point for post-Golgi trafficking of newly synthesized E-cadherin to the lateral plasma membrane.

Reason: Trans-Golgi network localization is non-core — reflects biosynthetic trafficking transit of E-cadherin before its delivery to the lateral plasma membrane. Core CC is plasma membrane/adherens junction.

Summary: The E-cadherin tail binds beta-catenin while also accommodating ankyrin-G.

Reason: Selected full PMID:17620337 Results and Figure 3 reconstitute E-cadherin/beta-catenin/ankyrin-G complexes and distinguish the partner-binding regions. Retain beta-catenin binding as a core activity; do not describe an associated spectrin molecule as directly bound to the cadherin tail.

Summary: E-cadherin is concentrated at lateral epithelial membranes.

Reason: The full primary study measures lateral-membrane E-cadherin and its dependence on ankyrin-G/spectrin, alongside mouse embryo experiments. The epithelial membrane localization is core, while the embryo species is kept distinct.

Summary: Ankyrin-G binds a distinct region of the E-cadherin cytoplasmic tail.

Reason: The original abstract directly supports this association and recruitment of the spectrin cytoskeleton. It is a regulatory/scaffolding partner interaction supporting membrane organization, retained outside the representative adhesive/catenin core.

Summary: E-cadherin recruits ankyrin-G to the plasma membrane in a cell-based assay.

Reason: Selected full PMID:17620337 Results and Figure 1C show ankyrin-G-GFP changing from cytoplasmic to plasma-membrane localization when coexpressed with E-cadherin in HEK293 cells; ankyrin-B is the comparison. This supports an E-cadherin recruiting/scaffold role, not merely its status as trafficking cargo. Retain the existing protein-localization process as non-core; an overexpression recruitment assay is not an unrestricted physiological transport mechanism.

Summary: Armus regulates E-cadherin junction disassembly and degradation.

Reason: The accessible primary abstract establishes Armus binding to active Rac1 and its Rab7 GAP activity, but does not resolve the exact E-cadherin/Armus binding assay. Preserve the original IPI claim as undecided pending that primary evidence, rather than infer binding because E-cadherin is its regulated cargo.

Summary: IDA from PMID:20189993: E-cadherin's cytoplasmic domain localizes to the cytoplasmic side of the plasma membrane where it interacts with beta-catenin, alpha-catenin, and p120-catenin. As a type-I transmembrane protein, E-cadherin's cytoplasmic tail is definitively on the cytoplasmic side of the plasma membrane, making this a correct CC annotation.

Summary: TAS from PMID:17047063: CDH1/E-cadherin localizes to cell junctions. GO:0030054 cell junction is a broad parent term; the precise and informative CC annotation is GO:0005912 adherens junction (ACCEPTed in this file), the specific junction type where E-cadherin resides and functions. Consistent with KEEP_AS_NON_CORE on the IEA cell junction annotation in this file.

Reason: Real but non-core CC -- CDH1 localizes to cell junctions but the precise junction type is the adherens junction (GO:0005912, accepted elsewhere); consistent with KEEP_AS_NON_CORE on the IEA cell junction row.

Summary: The precise CDH1 negative-adhesion experiment in the LEF1 paper remains unresolved.

Reason: The abstract reports effects of LEF1 perturbation on E-cadherin expression and aggregation; it does not establish that the curated experimental assertion is erroneous. The relevant full assay could not be recovered. Reverse the previous REMOVE and preserve the experimental source pending full evidence.

Summary: IDA from PMID:19038973: Cell junction localization of E-cadherin confirmed experimentally. GO:0030054 cell junction is the broad parent of GO:0005912 adherens junction; the precise core CC is the adherens junction, ACCEPTed elsewhere in this file.

Reason: Broad parent CC — GO:0030054 cell junction is a broader category than GO:0005912 adherens junction, the precise core CC for E-cadherin (ACCEPTed in this file). A real but non-core annotation: the informative term is the specific adherens junction. Action reconciled with the IEA and TAS GO:0030054 rows in this file.

Summary: E-cadherin is associated with a vinculin/beta-catenin junctional complex.

Reason: Full primary Methods identify full-length chick vinculin and human MCF10A cells, matching the cross-species GOA partner scope. The source describes beta-catenin-mediated recruitment, not necessarily direct E-cadherin/vinculin contact. Retain this reported complex association as non-core.

Summary: IDA from PMID:20086044: Adherens junction localization confirmed experimentally. Core CC for E-cadherin.

Summary: Indole-3-carbinol changes E-cadherin expression alongside migration and invasion phenotypes.

Reason: The accessible PMID:10868478 abstract reports dose-dependent E-cadherin/catenin induction and reduced invasion/migration, but does not resolve whether an E-cadherin-specific perturbation establishes participation in the drug response. The relevant full assay was not recovered. Preserve the experimental IDA assertion as undecided rather than equating expression induction with an executed response mechanism or confidently removing it.

Summary: IPI from PMID:1639850 (Knudsen and Wheelock 1992): Plakoglobin (gamma-catenin, JUP) co-immunoprecipitates with E-cadherin and N-cadherin. E-cadherin cytoplasmic tail interacts with plakoglobin/gamma-catenin (an 83-kD Drosophila armadillo/plakoglobin-like protein), linking E-cadherin to the cytoskeleton. Gamma-catenin binding is a core MF — plakoglobin is a functional component of the E-cadherin-catenin complex at adherens junctions and desmosomes.

Summary: IDA from PMID:10460003 (Smythe et al. 1999): E-cadherin and catenins detected at apical junction complexes in normal human bronchial epithelium by immunohistochemistry. The apical junction complex (AJC) is the composite apical unit comprising the tight junction, zonula adherens and desmosomes; E-cadherin resides specifically in the zonula adherens sub-compartment, so the annotation is accurate but broader than the precise core CC, GO:0005912 adherens junction.

Reason: Accurate but broader-than-precise CC grouping — the apical junction complex is the composite of tight junction, adherens junction and desmosomes; E-cadherin resides specifically in the zonula adherens, whose precise term GO:0005912 adherens junction is ACCEPTed as core in this file. Action reconciled with the IBA GO:0043296 row in this file.

Summary: Lithium induces E-cadherin expression in selected human lung-cancer cell lines.

Reason: Full PMID:12937339 Methods and Results/Figure 1 directly measure LiCl-dependent E-cadherin protein/mRNA induction, with inositol and histone-deacetylase-inhibitor comparisons. The demonstrated E-cadherin role here is the regulated readout. These assays do not establish that E-cadherin executes a step in lithium sensing or the response mechanism; the biological-process assignment is therefore over-annotated at this inspected scope, without disputing the experimental induction.

Summary: The Cdh1 in this source is the APC/C coactivator FZR1 rather than E-cadherin/CDH1.

Reason: Full Results/Figure 2D–G test Cdh1 with a deleted WD40 domain and purified His-Cdh1 in APC/C-associated ubiquitin-chain elongation. This is a construct-based citation-identity correction after reading the relevant full primary text, not an inference from the paper title. The original source tuple remains intact.

Summary: IDA from PMID:18593713 (Tang et al. 2008): Smad7 stabilizes the beta-catenin-E-cadherin complex at the plasma membrane. The catenin complex (GO:0016342) — comprising E-cadherin, beta-catenin, alpha-catenin, and p120-catenin — is the core protein complex mediating E-cadherin adhesion and cytoskeletal linkage. E-cadherin is the transmembrane scaffold of this complex.

Summary: IDA from PMID:16338932 (Peignon et al. 2006): E-cadherin-dependent cell-cell adhesion via adherens junctions studied using chimeric E-cadherin-Fc homophilic surfaces and Caco-2 enterocytes. Adherens junction is the core CC for E-cadherin in intestinal epithelial cells.

Summary: NAS from PMID:16338932 (Peignon et al. 2006): Homophilic cell-cell adhesion is the foundation for the experimental design (chimeric E-cadherin-Fc surfaces, Caco-2 cell-cell contacts) and is cited as established background knowledge. Homophilic cell-cell adhesion is the definitively core BP for E-cadherin — the basis for all adherens junction-mediated tissue cohesion.

Summary: The E-cadherin complex associates with the actin cytoskeleton through catenins.

Reason: The PMID:16338932 abstract explicitly describes E-cadherin-actin complexes in polarized Caco-2 enterocytes. Preserve the original colocalization context as non-core, without turning indirect cytoskeletal association into purified actin-binding activity.

Summary: E-cadherin is a membrane protein, with its main adhesive activity at the cell surface.

Reason: The membrane term is broad but correct. Retain it as non-core while the existing plasma-membrane and junctional annotations carry the useful spatial detail; breadth alone does not make this a biological over-annotation.

Summary: The lateral membrane is the principal epithelial E-cadherin compartment.

Reason: The original PMID:16338932 Caco-2 study is retained with independent primary lateral-membrane evidence from PMID:17620337. Only the abstract of the original paper was recovered; no uninspected figure is claimed as newly verified.

Summary: IDA from PMID:16338932 (Peignon et al. 2006): E-cadherin-dependent cell-cell adhesion promotes transcriptional activation of the apoA-IV gene via increased nuclear abundance of HNF4alpha. Positive regulation of transcription is an indirect downstream consequence of E-cadherin-mediated adhesion signaling.

Reason: Transcriptional activation of apoA-IV via HNF4alpha is an indirect downstream effect of E-cadherin signaling in intestinal enterocytes — a context-specific non-core function. E-cadherin's core function is homophilic cell-cell adhesion.

Summary: The exact perinuclear E-cadherin localization assay remains unresolved.

Reason: Only the abstract of PMID:16338932 was available in the normal cache; it emphasizes HNF4alpha redistribution but does not exclude an E-cadherin localization experiment in the full text. The previous claim of misattribution was unsupported. Preserve the original IDA assertion as undecided.

Summary: The source uses an E-cadherin-Fc homophilic ligand to engage cell-surface E-cadherin.

Reason: The primary abstract identifies a cadherin ligand explicitly, so refine the broad cell-adhesion-molecule-binding term to cadherin binding. This does not assign DNA binding or HNF4alpha transcription-factor activity to E-cadherin. The soluble E-cadherin-Fc presentation tests cadherin engagement without independently establishing an opposing-cell ligand in that particular assay, so this source-specific refinement remains cadherin binding rather than automatically adopting the core cell-cell-adhesion-qualified term.

Proposed replacements: cadherin binding

Summary: IDA from PMID:16338932 (Peignon et al. 2006): Cell-cell adhesion confirmed directly — E-cadherin mediates Caco-2 enterocyte cell-cell adhesion; impairing or enhancing E-cadherin-dependent adhesion modulates apoA-IV transcription. Cell-cell adhesion (GO:0098609) is core BP for E-cadherin.

Summary: NAS from PMID:8033105: Homophilic cell-cell adhesion is the foundational and defining function of E-cadherin — a classical cadherin mediating Ca2+-dependent homophilic trans-adhesion between cells via strand-swap dimerization of the EC1 domain. This is the core BP and mechanism for E-cadherin's role in epithelial tissue integrity and morphogenesis.