CDH11

Summary: Adhesive contacts contribute to cell shape and organization.

Reason: The PAINT inference is consistent with CDH11-dependent changes in cell shape and multicellular organization. Retain this broad morphogenetic outcome as non-core; direct adhesion and junction organization give the more informative account of its molecular role. The ancestral node was not independently re-curated.

Summary: Skeletal development is a supported tissue context.

Reason: The original cloning paper proposes a bone-forming role rather than establishing a developmental mechanism. Later mouse Cdh11 deletion reduces calvarial and metaphyseal bone density; human osteoblasts express junctional CDH11. Retain the historical TAS assertion as non-core with this independent support, preserving its original evidence.

Summary: Ossification is an adhesive tissue-level role.

Reason: The historical NAS annotation is suggestive in its original source. Mouse Cdh11-null calvarial cells subsequently showed reduced mineralized area, supporting a conserved contribution to bone formation. This does not assign CDH11 mineral-catalyzing activity or make bone formation its defining molecular function.

Summary: Adhesion-dependent valve maturation is supported in animal models.

Reason: The source includes mouse knockout valve defects and porcine/chick valve-cell migration assays. WITH F1RFU7 resolves to pig CDH11. Retain the curated ISS transfer as a non-core developmental context, without relabeling it as a direct human valve experiment or attributing RhoA catalysis to CDH11.

Summary: Calcium binding supports the adhesive ectodomain.

Reason: The cadherin-repeat InterPro mapping is consistent with calcium-dependent adhesion and conserved extracellular calcium-binding architecture. Retain this broad cofactor-binding annotation as non-core; the more informative defining activity is cell-cell adhesion mediated by the extracellular domain.

Summary: A released CDH11 fragment is extracellular.

Reason: Reactome explicitly models cleavage of the canonical membrane protein to a secreted extracellular fragment and a membrane remnant. The human splice-variant study independently reports the secreted form. Retain the location for this processed product; the exact cleavage site remains unspecified.

Summary: The specific cytoplasmic localization remains unresolved.

Reason: The electronic transfer traces to mouse Cdh11 IDA evidence from PMID12139922. Its accessible abstract establishes a developmental localization study, but not the exact intracellular pool underlying this term. A cytoplasmic tail alone does not establish whole-protein cytoplasmic localization; preserve the inference pending that source detail.

Summary: Plasma membrane is the principal site of CDH11 adhesion.

Reason: Independent human CDH11 surface-expression and adhesion experiments support the location indicated by the combined electronic sources. This does not depend on reconstructing every ARBA or orthology rule; the original qualifier and source entities are preserved.

Summary: The source places CDH11 at the plasma membrane.

Reason: The reaction explicitly locates the cadherin participating in trans-cellular adhesion at the plasma membrane.

Summary: The source places CDH11 at the plasma membrane.

Reason: The membrane cadherin recruits cytoplasmic catenins at cell contacts; this location does not transfer catenin enzymatic or actin-binding activities to CDH11.

Summary: The source places CDH11 at the plasma membrane.

Reason: The canonical CDH11 translation product is represented at the plasma membrane. This is a product localization, not participation of CDH11 in its own translation.

Summary: The source places CDH11 at the plasma membrane.

Reason: The source specifically represents tail-truncated CDH11 isoform2 at the cell surface. Location is retained without transferring the canonical tail’s catenin-binding properties to that isoform.

Summary: The source places CDH11 at the plasma membrane.

Reason: The source includes the membrane-bound precursor and retained membrane fragment as well as the separate released ectodomain.

Summary: The source places CDH11 at the plasma membrane.

Reason: The CDH11–catenin association is represented at the plasma membrane, consistent with the independent human CDH11 junctional assays.

Summary: The source places CDH11 at the plasma membrane.

Reason: The AMOT interaction is modeled on the membrane-localized CDH11 tail; no AMOT molecular activity is assigned to CDH11.

Summary: The source places CDH11 at the plasma membrane.

Reason: The source places the CDH11 receptor for the extracellular ANGPTL4 fragment at the plasma membrane.

Summary: The source places CDH11 at the plasma membrane.

Reason: CDH11 remains a membrane protein in the modeled release of bound beta-catenin; it is beta-catenin that is released to the cytosol.

Summary: The source places CDH11 at the plasma membrane.

Reason: The source represents membrane-localized CDH11 variant isoform binding ANGPTL4, explicitly without canonical beta-catenin binding.

Summary: The source places CDH11 at the plasma membrane.

Reason: This is a deliberately chimeric human CDH11/mouse catenin event based on human CDH11 expressed in mouse L cells. The R-NUL identifier does not invalidate the human protein’s measured membrane location.

Summary: CDH11 functions at adherens junctions.

Reason: Human CDH11 expressed in mouse L cells accumulates with catenins at cell-cell contacts; tail-domain perturbation alters junction organization. This independently corroborates the PAINT assertion and its is_active_in qualifier, without treating the family inference as a pairwise donor transfer.

Summary: CDH11 supports assembly of adhesive cell-cell junctions.

Reason: The full-length human protein enables organized intercellular contacts, whereas its beta-catenin-binding-tail truncation impairs them in the L-cell model. The source-derived IBA is biologically coherent with this direct structural contribution to junction assembly.

Summary: Cell adhesion is the central CDH11 role.

Reason: The broad InterPro-derived process is a correct parent of the experimentally established homophilic adhesive mechanism. Retain it as core; the core synthesis states the more precise cadherin-mediated process rather than repeating every ancestor.

Summary: The historical cell-adhesion assertion is correct.

Reason: The original mouse cloning study demonstrates calcium-dependent adhesive acquisition and identifies human CDH11 isoforms. Later human-protein assays independently establish adhesion, so the broad TAS annotation is sound while its original provenance is retained.

Summary: CDH11 mediates homophilic cell-cell adhesion.

Reason: Human CDH11-positive cells specifically engage immobilized CDH11 ectodomain and form cohesive cell contacts. This corroborates the electronic cadherin-domain inference; a ligand-coated plate is an assay of the homophilic mechanism rather than evidence for a distinct extracellular-matrix ligand.

Summary: The canonical CDH11 tail recruits beta-catenin.

Reason: Retain the PAINT molecular-function assertion. Human CDH11 tail-deletion experiments delimit the beta-catenin-recruiting region, and human osteoblast work independently supports catenin-associated junctional CDH11. This activity is not generalized to tail-truncated isoform2 or equated with beta-catenin transcriptional activity.

Summary: Membrane localization is a correct broad parent.

Reason: CDH11 is a single-pass surface protein. The broad InterPro-derived location remains correct, while the plasma membrane is specified by the independent localization rows and core functions. A more specific location is already represented rather than newly asserted.

Summary: Calcium-dependent adhesion is a defining CDH11 process.

Reason: The cadherin-domain inference is consistent with the original calcium-dependent aggregation result and later calcium-containing human-protein adhesion assays. Retain the family-level IBA as core; it does not require a new independent human ion-binding kinetic experiment.

Summary: Canonical CDH11 participates in catenin-containing adhesion complexes.

Reason: The intact human cytoplasmic tail recruits catenins at adhesive contacts; removing the distal tail disrupts beta/alpha-catenin recruitment. Retain the curated IBA complex membership. This refers to canonical junctional CDH11 and does not imply that every splice product binds catenins.

Summary: CDH11 coordinates movement along adhesive cell contacts.

Reason: Human CDH11 engagement promotes L-cell migration on CDH11-coated substrates and intercalation into cell layers; its cytoplasmic-domain mutants separate these effects from surface expression. This supports the PAINT process inference as an adhesion-coupled core role, without asserting a universal direction of migration regulation.

Summary: The supported migration inference describes a core adhesive role.

Reason: The pig WITH accession matches porcine valve-cell experiments; mouse and chick assays provide additional context. Retain ISS provenance. Because the existing assertion is unqualified cell migration, it represents the same adhesion-coupled core process as the IBA row, without turning an ortholog result into a human experiment.

Summary: CDH11 can restrain migration in the tested fibroblast context.

Reason: PMID33811546 Fig5e compares E279Q patient fibroblasts with controls and finds faster wound closure, without a measured proliferation difference. Retain this perturbation-based negative-regulation annotation as contextual, not a universal anti-migratory property.

Summary: CDH11 contributes to cell-substrate adhesion through focal-adhesion organization.

Reason: The original patient fibroblasts show altered spreading and immature paxillin-positive focal adhesions (Fig.5b–d), while initial substrate attachment is comparable to controls through 2 hours (Fig.S4C). The CDH11-Fc plate assay alone measures homophilic trans adhesion and is not the basis for this process. Independent PMID26952325 establishes a direct structural contribution in Xenopus neural crest: CDH11 transmembrane/cytoplasmic regions support fibronectin adhesion through a syndecan-4 complex, with loss/rescue and force assays; syndecan-4 supplies the extracellular fibronectin recognition. That study also localizes endogenous CDH11 to focal adhesions in human HFF-1 fibroblasts. Together these support a conserved non-core contribution, while preserving the original IMP source and distinguishing ortholog mechanism from human localization. No intrinsic CDH11 fibronectin- or integrin-binding activity is inferred.

Summary: CDH11 organizes catenin-linked adherens junctions.

Reason: Its own adhesive and catenin-recruiting domains establish intercellular contacts whose organization changes with tail deletion. This supports the PAINT process assertion, with direct human-protein evidence in a mouse-cell host; the PAINT node itself was not reconstructed.

Summary: Pathological fibrosis evidence is broader than normal skin development.

Reason: Exact mouse donor evidence points to PMID29112946, which tests antibody inhibition of hypodermal fibrosis in Tsk-1 mice at 5–9 weeks. GO0043588 describes progression of skin from formation to mature structure. The fibrosis results are valid, but do not establish that developmental process for this human transfer; flag the term’s scope rather than deny CDH11-dependent fibroblast behavior.

Summary: CDH11 itself mediates cadherin-dependent cell-cell adhesion.

Reason: The extracellular domain supplies the trans interaction between cells. Human-protein adhesion and contact-formation experiments corroborate the PAINT assertion, so this is participation by the gene product itself rather than inference from disease severity alone.

Summary: Synaptic localization is supported by the mouse donor evidence.

Reason: The Ensembl transfer traces to SynGO annotations from PMID10860580. Its abstract reports hippocampal synaptic neuropil and synaptophysin/GluR1-associated localization. Retain this conserved neural context as non-core, with the source orthology and is_active_in qualifier preserved; no direct human synaptic assay is claimed.

Summary: CDH11 binds cadherins; the cadherin binding (GO:0045296) genus is correct as it stands, and the cell-cell adhesion context is carried by the core functions rather than by the precomposed GO:0098641.

Reason: The genus GO:0045296 is the right term. An earlier pass proposed MODIFY to the precomposed GO:0098641; per projects/INVOLVED_IN_PRECOMPOSITION.md that adds only the cell-cell adhesion context, which is carried by the core functions. Evidence retained from the earlier reasoning: human CDH11 on cells binds the CDH11 ectodomain and establishes cell-cell contacts; independent human assays support the activity, while the PAINT ancestral node was not re-curated.

Summary: CDH11 perturbation alters focal-adhesion maturation.

Reason: Patient E279Q fibroblasts contain immature paxillin-positive focal adhesions and abnormal actin organization (PMID33811546 Fig5c). Retain the existing IMP process as a contextual consequence of CDH11-dependent cell organization, not proof of an intrinsic integrin-binding activity.

Summary: Cadherin-11 contributes to synaptic plasticity in the donor model.

Reason: Mouse Cdh11 deletion enhances CA1 long-term potentiation in PMID10860580. The exact SynGO donor linkage supports retention of the broader modulation term as a non-core ortholog inference; it does not make CDH11 a neurotransmitter receptor or demonstrate the same effect directly in humans.

Summary: The exact exosomal CDH11 protein-list entry was not recovered.

Reason: The full source describes proteomics of human expressed-prostatic-secretions/urine exosome preparations. Its target list is Supplementary Table2, whose download returned a preparation page and whose Europe PMC endpoint is unavailable. Preserve the curator’s HDA assertion pending target-level confirmation; do not infer exosome biogenesis or reject localization merely because it is non-core.

Summary: Cell-cell adhesion is the core process.

Reason: This electronic annotation is a correct parent of CDH11-mediated homophilic adhesion. The human-protein assays support the process independently of the domain mapping; the more specific cadherin-mediated process is used in the core synthesis.

Summary: The source donor acts at hippocampal CA1 synapses.

Reason: QuickGO resolves the mouse donor’s exact SynGO CA1-synapse annotation to the electrophysiology study PMID10860580. Retain the human orthology transfer as a specialized non-core neural location, without converting its evidence to direct human localization.

Summary: Glutamatergic-synapse localization is a supported donor context.

Reason: The mouse SynGO record derives from hippocampal localization assays in PMID10860580, whose abstract reports occasional GluR1 overlap at spines. Retain the source-qualified orthology inference as non-core; detailed human subcompartment localization remains outside the directly tested scope.