DSC2

Summary: DSC2 is included in a cornified-envelope desmosomal network.

Reason: The current ARBA00028309 conditions match the target. Independently, the Reactome cornified-envelope output contains DSC2 Q02487 residues 136–901 through a desmocollin member set and a desmosome/keratin network. Retain this differentiated epithelial compartment as contextual localization, without assigning DSC2 the proteolytic steps that mature the envelope.

Summary: The cornified-envelope model includes DSC2 as a structural component.

Reason: The source event and its downstream mature cornified-envelope entity retain DSC2 through the desmosome/keratin network. This is a tissue-specific structural location, not evidence that DSC2 performs filaggrin cleavage or other enzymatic envelope-maturation steps.

Summary: Calcium binding supports the extracellular cadherin architecture.

Reason: The exact 901-residue target matches the PANTHER alignment and descends from PTN001931974, which carries the literal calcium-binding IBD. The fly CadN structural donor and rat desmoglein-4 calcium-site evidence ground the ancestral assertion; donor count and target self-evidence are not used to discount PAINT. Target ectodomain and calcium-dependent binding experiments independently fit this conserved activity.

Summary: The cadherin-domain prediction of calcium binding is biologically supported.

Reason: The listed InterPro entries are present on the official target and describe its cadherin architecture. The calcium-associated ectodomain structure and calcium-sensitive binding experiments support this activity as part of the adhesive mechanism, without claiming that every interdomain interface binds the same number of ions.

Summary: Human DSC2 tails associate with plakophilin-2 in the plaque-linkage assay.

Reason: The literal partner F1M7L9 is rat plakophilin-2. Human DSC2a and DSC2b cytoplasmic tails capture it from rat-heart lysate. Plakophilin-2 is an armadillo-repeat plaque protein in the cadherin–intermediate-filament linkage, not a filament-forming subunit. GO:0008092 covers binding a protein component of the cytoskeleton; the partner's documented intermediate-filament and plaque-protein interactions, together with curated intermediate-filament component assignments, support this broad class. Those rat/human component annotations are ortholog-based and are not relabeled as direct rat localization experiments. The DSC2 assay establishes lysate association, not purified binary contact, and does not imply that all cellular PKP2 pools or both DSC2 products have identical functions. Specifically, rat F1M7L9 has GO:0005882 ISO from MGI:1914701 (GO_REF:0000121), human Q99959 has GO:0005882 ISS from Q9CQ73 (GO_REF:0000024), and mouse Q9CQ73 has the corresponding IDA annotation from PMID:16917092. GO:0005882 is within the current GO:0005856 cytoskeleton closure. The donor experiment is retained as a curated assertion; its full PKP2-specific assay was not independently recovered.

Proposed replacements: cytoskeletal protein binding

Summary: The longer human DSC2a tail associates with a desmoplakin fragment.

Reason: The source compares human DSC2a/DSC2b tails and a human desmoplakin N-terminal construct in a transfected-cell assay. The DSC2a association and the desmoplakin intermediate-filament linkage function support cytoskeletal protein binding. The short DSC2b tail lacks this association in the reported comparison; neither purified affinity nor equivalence of the natural products is asserted.

Proposed replacements: cytoskeletal protein binding

Summary: The longer DSC2a tail associates with plakoglobin, the gamma-catenin subunit.

Reason: The literal partner Q6P0K8 is rat plakoglobin/JUP. Human DSC2a tail captures plakoglobin from rat-heart lysate, whereas the DSC2b tail does not in the reported assay. GO:0045295 specifically names gamma-catenin binding and preserves this identified partner class and product distinction. A lysate association is not presented as a purified human–human interface measurement.

Proposed replacements: gamma-catenin binding

Summary: The source reports DSC2 association with desmoglein-2; modified to cadherin binding, with the cell-cell adhesion context in the core functions.

Reason: The replacement is the genus GO:0045296 cadherin binding rather than the precomposed GO:0098641 (projects/INVOLVED_IN_PRECOMPOSITION.md); the cell-cell adhesion context is carried by the core functions. Evidence retained from the earlier reasoning: Supplementary Figure S5B provides a controlled DSG2-GFP co-immunoprecipitation with DSC2, with input and empty-GFP controls; IntAct EBI-6901957 / IM-20978-13 records anti-tag co-immunoprecipitation (MI:0007) and physical association (MI:0915). Independently, the human ectodomain SPR and bead-adhesion experiments in PMID:27298358 establish this same DSC2–DSG2 pair as an adhesive cadherin interaction. This does not relabel the 2011 co-IP as a purified trans-cell adhesion assay or resolve natural cytoplasmic-product equivalence.

Proposed replacements: cadherin binding

Summary: DSC2 self-association is observed in defined experimental constructs and conditions.

Reason: The 2016 paper reports a weak DSC2 homodimeric crystal contact in a construct containing DSC2 EC1 and DSG2 EC2–5, while solution DSC2 self-association is very weak and DSC2-coated beads do not aggregate. Complementary 2014/2018 single-molecule experiments detect DSC2 self-binding. Identical protein binding is supported without converting the crystal contact into exclusive native homophilic adhesion or rejecting the positive source assertion.

Proposed replacements: identical protein binding

Summary: DSC2–DSG2 binding directly supports a cadherin adhesion activity; modified to cadherin binding, with the cell-cell adhesion context in the core functions.

Reason: The replacement is the genus GO:0045296 cadherin binding rather than the precomposed GO:0098641 (projects/INVOLVED_IN_PRECOMPOSITION.md); the cell-cell adhesion context is carried by the core functions. Evidence retained from the earlier reasoning: The 2022 study includes DSC2 and DSG2 ectodomains, but its supplementary affinity table attributes the DSC2–DSG2 29,000 nM value to the previously published 2016 study. The source-data network explicitly labels that affinity as Published. The independent 2016 human ectodomain SPR and bead-adhesion experiments establish the DSC2–DSG2 adhesive cadherin binding. Raw 2022 screening values are not relabeled as new high-affinity validation; the DSC2 ectodomain sequence shared by both natural products does not establish identical cytoplasmic-tail behavior.

Proposed replacements: cadherin binding

Summary: The source localizes functional DSC2 at desmosomal cell contacts.

Reason: The human DSC2 constructs and junctional localization/interaction experiments establish the desmosomal adhesive pool more specifically than plasma membrane. Use desmosome while retaining the source’s separate vesicular and overexpression observations in their own review. Human constructs in monkey or rodent hosts are not described as endogenous human-cell localization.

Proposed replacements: desmosome

Summary: HPA supports a plasma-membrane pool; its additional endoplasmic-reticulum observation has uncertain location-specific reliability.

Reason: The HPA target ENSG00000134755/Q02487, assessed with antibody HPA012615, has supported plasma-membrane localization in the summary and plasma-membrane staining in HaCaT, SuSa and U-2 OS cells. The same source records additional endoplasmic-reticulum staining in HaCaT and SuSa but rates that location uncertain. Overall gene reliability is supported and must not be substituted for the individual ER score. Preserve the positive broader plasma-membrane pool as contextual localization because this source does not resolve all signal to desmosomes. Retain ER as an uncertain observation rather than an established additional compartment; no new image-pixel interpretation is claimed.

Summary: Wild-type human DSC2a localizes to desmosomal contacts in cardiac-cell assays.

Reason: The original uses sequence-verified human DSC2a-GFP and tests localization in neonatal rat cardiomyocytes and HL-1 cells. Wild-type junctional/desmosomal targeting is supported and differs from the disease-variant cytoplasmic distribution. Desmosome captures the relevant wild-type membrane pool without treating rodent host cells as human tissue.

Proposed replacements: desmosome

Summary: The source observes wild-type DSC2 at the cell surface and at cardiac intercalated discs.

Reason: The accessed main-text Methods and Results include human DSC2b-GFP in HeLa/HEK293 cells and patient cardiac tissue. The wild-type membrane observation is broader than a resolved desmosomal subdomain in every assay, so it is retained as a nonexclusive contextual pool. Mutant Q554X distribution and proposed secretion are not treated as normal wild-type topology; the intercalated-disc evidence is reviewed separately.

Summary: The electronic plasma-membrane assignment can be refined to the desmosomal adhesive pool.

Reason: The target is a type-I desmosomal cadherin, and the mapped family/subcellular-location assertion is independently supported by human cardiac and epithelial junction experiments. Desmosome names the mechanistically established adhesive membrane specialization; this refinement is not a claim that DSC2 never occupies broader plasma-membrane or secretory-transport pools.

Proposed replacements: desmosome

Summary: The Reactome event carries DSC2 in a desmosomal membrane component.

Reason: The exact Reactome:R-HSA-6809393 participant/output graph has a positive path through a desmosome and desmocollin member set to DSC2 Q02487 residues 136–901. Refine this modeled membrane component to desmosome. Its presence in the graph does not make DSC2 the enzyme responsible for the event’s proteolytic, phosphorylation or cross-linking chemistry, and it is not an independent localization experiment.

Proposed replacements: desmosome

Summary: The Reactome event carries DSC2 in a desmosomal membrane component.

Reason: The exact Reactome:R-HSA-6810357 participant/output graph has a positive path through a desmosome and desmocollin member set to DSC2 Q02487 residues 136–901. Refine this modeled membrane component to desmosome. Its presence in the graph does not make DSC2 the enzyme responsible for the event’s proteolytic, phosphorylation or cross-linking chemistry, and it is not an independent localization experiment.

Proposed replacements: desmosome

Summary: The Reactome event carries DSC2 in a desmosomal membrane component.

Reason: The exact Reactome:R-HSA-6810937 participant/output graph has a positive path through a desmosome and desmocollin member set to DSC2 Q02487 residues 136–901. Refine this modeled membrane component to desmosome. Its presence in the graph does not make DSC2 the enzyme responsible for the event’s proteolytic, phosphorylation or cross-linking chemistry, and it is not an independent localization experiment.

Proposed replacements: desmosome

Summary: The Reactome event carries DSC2 in a desmosomal membrane component.

Reason: The exact Reactome:R-HSA-6811539 participant/output graph has a positive path through a desmosome and desmocollin member set to DSC2 Q02487 residues 136–901. Refine this modeled membrane component to desmosome. Its presence in the graph does not make DSC2 the enzyme responsible for the event’s proteolytic, phosphorylation or cross-linking chemistry, and it is not an independent localization experiment.

Proposed replacements: desmosome

Summary: The Reactome event carries DSC2 in a desmosomal membrane component.

Reason: The exact Reactome:R-HSA-6814298 participant/output graph has a positive path through a desmosome and desmocollin member set to DSC2 Q02487 residues 136–901. Refine this modeled membrane component to desmosome. Its presence in the graph does not make DSC2 the enzyme responsible for the event’s proteolytic, phosphorylation or cross-linking chemistry, and it is not an independent localization experiment.

Proposed replacements: desmosome

Summary: The Reactome event carries DSC2 in a desmosomal membrane component.

Reason: The exact Reactome:R-HSA-6814387 participant/output graph has a positive path through a desmosome and desmocollin member set to DSC2 Q02487 residues 136–901. Refine this modeled membrane component to desmosome. Its presence in the graph does not make DSC2 the enzyme responsible for the event’s proteolytic, phosphorylation or cross-linking chemistry, and it is not an independent localization experiment.

Proposed replacements: desmosome

Summary: The Reactome event carries DSC2 in a desmosomal membrane component.

Reason: The exact Reactome:R-HSA-6814695 participant/output graph has a positive path through a desmosome and desmocollin member set to DSC2 Q02487 residues 136–901. Refine this modeled membrane component to desmosome. Its presence in the graph does not make DSC2 the enzyme responsible for the event’s proteolytic, phosphorylation or cross-linking chemistry, and it is not an independent localization experiment.

Proposed replacements: desmosome

Summary: The Reactome event carries DSC2 in a desmosomal membrane component.

Reason: The exact Reactome:R-HSA-6814734 participant/output graph has a positive path through a desmosome and desmocollin member set to DSC2 Q02487 residues 136–901. Refine this modeled membrane component to desmosome. Its presence in the graph does not make DSC2 the enzyme responsible for the event’s proteolytic, phosphorylation or cross-linking chemistry, and it is not an independent localization experiment.

Proposed replacements: desmosome

Summary: The Reactome event carries DSC2 in a desmosomal membrane component.

Reason: The exact Reactome:R-HSA-6814764 participant/output graph has a positive path through a desmosome and desmocollin member set to DSC2 Q02487 residues 136–901. Refine this modeled membrane component to desmosome. Its presence in the graph does not make DSC2 the enzyme responsible for the event’s proteolytic, phosphorylation or cross-linking chemistry, and it is not an independent localization experiment.

Proposed replacements: desmosome

Summary: The Reactome event carries DSC2 in a desmosomal membrane component.

Reason: The exact Reactome:R-HSA-8942224 participant/output graph has a positive path through a desmosome and desmocollin member set to DSC2 Q02487 residues 136–901. Refine this modeled membrane component to desmosome. Its presence in the graph does not make DSC2 the enzyme responsible for the event’s proteolytic, phosphorylation or cross-linking chemistry, and it is not an independent localization experiment.

Proposed replacements: desmosome

Summary: The general cell-cell junction assertion is supported, with desmosome providing the specific location.

Reason: The current ARBA00028427 rule does not replay against the current target condition sets, so the historical rule provenance remains unresolved rather than being called erroneous. Independent human DSC2 desmosomal evidence clearly supports the biological junction assertion and its refinement to desmosome.

Proposed replacements: desmosome

Summary: The transferred adherens-junction localization requires source-specific resolution.

Reason: The current mouse P55292 record contains an IDA adherens-junction annotation from PMID:15775979. The accessible abstract, indexed figure context and incomplete main-branch HTML extract describe mouse epidermal junction analysis. The extract is flagged full text but omits the operative Figure 2/3 Results and Methods; the complete target-specific original and supplement were not recovered. GO:0005912 refers to an E-cadherin/catenin adherens junction, distinct from desmosome. Preserve the donor and human assertion while leaving this narrower compartment unresolved; the title’s focus on E-cadherin is not evidence of misattribution.

Summary: DSC2 directly participates in adhesion between cells.

Reason: The desmocollin-family assignment is correct, but cell adhesion also includes cell-matrix adhesion. DSC2’s established extracellular adhesive work is cell-cell adhesion, supported by ectodomain binding and cardiac/epithelial junction experiments. GO:0098609 is the appropriate cross-tissue core process; the separate cardiac and epithelial annotations retain their finer experimental contexts.

Proposed replacements: cell-cell adhesion

Summary: The alternatively spliced desmocollin products contribute to cell-cell adhesion.

Reason: The 1991 source establishes human desmocollin cDNAs and alternative cytoplasmic tails; its full original was only partially accessible. Independent human ectodomain and cellular evidence establishes the adhesive process more specifically as cell-cell adhesion. This refinement does not claim that the 1991 cloning study measured all adhesive mechanisms or that the two products have identical plaque coupling.

Proposed replacements: cell-cell adhesion

Summary: Homophilic DSC2 binding can support adhesion under defined assay conditions.

Reason: The broad cadherin-repeat mapping alone does not establish exclusive homophilic specificity. Nevertheless, the 2014/2018 studies provide positive calcium-dependent DSC2 self-binding and functional substrate/contact observations, whereas the 2016 bulk and bead assays favor heterophilic DSC2–desmoglein adhesion. Retain homophilic adhesion as a bounded context rather than rejecting the positive experiments or making it the universal native arrangement.

Summary: DSC2 is a component of cardiac intercalated discs.

Reason: The human DSC2 construct experiments and cardiac localization/partner assays support this tissue-specific junctional compartment. The original distinguishes DSC2a and DSC2b tail interactions and uses rodent cardiac material and nonhuman transfection hosts in part; no all-product or all-assay human-cell equivalence is asserted.

Summary: Cardiac tissue and cell experiments support DSC2 localization at intercalated discs.

Reason: The source includes human patient cardiac biopsy material and defined human DSC2 constructs in neonatal rat cardiac and HL-1 cells. It examines desmosomal/cadherin and gap-junction organization in this compartment. The intercalated-disc localization is retained without transferring every mutant effect to wild type or claiming that DSC2 is itself a connexin channel.

Summary: Human cardiac material supports intercalated-disc DSC2 localization.

Reason: The accessed original main text includes cardiac tissue staining and wild-type DSC2 membrane/junction observations. Intercalated-disc localization is supported even though the separate His–Purkinje and ventricular action-potential claims cannot be verified at the same anatomical/physiological resolution from the recovered source windows.

Summary: The general membrane prediction is refined to the desmosomal adhesive pool and independently supported broader plasma-membrane localization.

Reason: The official target is a single-pass desmosomal cadherin. Human cardiac and epithelial junction experiments establish desmosome as its adhesive specialization. HPA independently supports plasma-membrane localization, with staining in HaCaT, SuSa and U-2 OS cells that is not resolved entirely to desmosomes. Retain desmosome and plasma membrane as complementary supported pools. The HPA page and downloadable location record rate the additional ER observation uncertain, despite the overall gene reliability being supported. That location-specific uncertainty, rather than absence from the GOA import or an assumed transit mechanism, is the reason not to propose ER here. The uncertain HaCaT/SuSa observation remains documented. This biological specificity judgment does not assert a missing desmosome-to-membrane ontology edge.

Proposed replacements: desmosome plasma membrane

Summary: The PAINT desmosome assertion is supported by target and family evidence.

Reason: The exact target sequence and descent from PTN002771418 were reconstructed, and the literal node IBD contains the desmosome assertion. Direct human DSC2 junction studies independently support the location. The target appearing among the extant sources is legitimate experimental grounding, not circular evidence.

Summary: Wild-type DSC2a is targeted to desmosomal contacts.

Reason: The original sequence-verified human DSC2a-GFP experiments compare wild type and disease variants in neonatal rat cardiomyocytes and HL-1 cells. Wild-type junctional localization and the variant targeting defects support desmosomal localization, with species and transgene boundaries retained.

Summary: DSC2 occupies desmosomal junctions and couples to plaque proteins.

Reason: The source’s localization and tail-interaction experiments support the desmosomal role. Human DSC2a/b products are experimentally distinguished: both tails associate with plakophilin-2, whereas the longer tail supports plakoglobin and desmoplakin-fragment association in the reported assays.

Summary: The source directly assesses DSC2 in cardiac desmosomal structures.

Reason: Human biopsy and human DSC2 transgene experiments in cardiac-cell models support localization within the desmosomal apparatus. Altered mutant distribution and connexin-43 organization are retained as contextual outcomes, not treated as evidence that DSC2 itself forms a gap-junction channel.

Summary: The combined orthology and curated-location inference agrees with direct target desmosomal localization.

Reason: The current mouse Dsc2 record contains desmosomal localization evidence, and the UniProt subcellular-location mapping names desmosome. Independent human DSC2 localization and adhesive experiments corroborate transfer; no claim of identical regulation or product behavior across species is required.

Summary: A cytoplasmic-vesicle pool is observed in the source’s expression/localization experiments.

Reason: The paper reports vesicular/Golgi-associated distribution in addition to junctional targeting, including expression-dependent effects. Retain the actual vesicle observation as contextual localization without defining DSC2 as a vesicle-biogenesis factor, asserting a specific vesicle subtype, or replacing normal junctional localization with the overexpression pattern.

Summary: The source’s self-association is specifically a homodimerization observation.

Reason: Refine the positive self-interaction to protein homodimerization activity. The 2016 structural contact involves a DSC2 EC1-containing chimera and weak self-association at high concentration, while bulk bead adhesion is negative for DSC2 self-pairs. Complementary single-molecule studies support self-binding. The refinement preserves the measured molecular interaction without asserting that this is the exclusive physiological adhesive unit.

Proposed replacements: protein homodimerization activity

Summary: DSC2 and desmoglein-2 form a heterotypic adhesive pair.

Reason: The source directly measures human ectodomain DSC2–DSG2 binding and adhesive bead association. Protein heterodimerization is more specific than generic protein dimerization for the literal Q02487/Q14126 pair. The heterodimer arrangement is inferred from biophysical and modeling evidence rather than a solved DSC2–DSG2 heterodimer crystal structure.

Proposed replacements: protein heterodimerization activity

Summary: DSC2 was identified in the urinary exosome-enriched proteome.

Reason: The original describes pooled healthy-human urinary low-density vesicle preparations and LC-MS/MS. Its linked NIH laboratory database lists DSC2/NP_004940 with one peptide assigned to the 2009 study. This positive proteomic localization is retained as contextual evidence; the database’s isoform-b label does not establish a uniquely mapped natural product without peptide-level sequence resolution, and detection does not establish an exosome-specific function.

Summary: The source-specific DSC2 assignment in the parotid exosome proteome remains unverified.

Reason: The genuine main original describes an exosome-enriched human parotid-saliva preparation, protein-level controls and an identification list, but the target-containing supplementary table was not recovered after bounded attempts. Preserve the curator’s positive HDA assertion rather than treating the absent table as a negative result. The independently recovered urinary observation does not identify the particular salivary peptide evidence.

Summary: The DSC2 peptide assignment in the expressed-prostatic-secretion urine proteome remains unverified.

Reason: The genuine main original describes pooled human cancer/noncancer urine preparations, vesicle enrichment and LC-MS/MS, but the target-specific supplementary identification table remains inaccessible. This is an access and source-resolution limit, not a conclusion that DSC2 is absent from the preparation or that the curator used the wrong gene.

Summary: DSC2 contributes directly to adhesion between cardiac muscle cells.

Reason: The source places DSC2 in cardiac desmosomes and tests human DSC2 tail coupling to plaque proteins in cardiac-cell/lysate contexts. Together with the independently measured extracellular adhesive activity, DSC2 supplies the transmembrane adhesive structure rather than merely being a disease marker necessary for an unrelated process. The natural-tail differences are retained.

Summary: The narrow bundle-of-His–Purkinje adhesion claim cannot be resolved from the recovered source.

Reason: The accessed main-text clinical, transfection and cardiac-biopsy material supports human DSC2 disease association and junctional localization, but does not establish the specific His-cell/Purkinje-cell interface at the resolution required by GO:0086073. The supplement was not recovered. Retain the original positive IMP assertion without claiming that the complete study lacks relevant evidence or confusing general cardiac adhesion with this anatomical subtype.

Summary: The inferred binding role in His–Purkinje communication depends on an unresolved anatomical claim.

Reason: The source infers this specific binding activity from GO:0086073. General DSC2 adhesive activity is well supported, but the recovered original windows do not resolve the bundle-of-His–Purkinje communication setting and the supplement remains unavailable. Preserve the source assertion and its inference basis; do not substitute generic cardiac adhesion as proof of the narrower activity.

Summary: The exact heart-rate regulation claim is not established by the recovered clinical conduction evidence alone.

Reason: The original reports clinical electrical/conduction observations and DSC2 disease-associated cellular phenotypes. GO:0086091 specifically concerns changing heart rate through cardiac conduction; neither disease association nor a conduction abnormality alone identifies DSC2’s particular rate-regulatory contribution. The complete supporting supplement is unavailable, so this is uncertainty about source scope, not a rejection of the positive curator annotation.

Summary: The mouse-to-human epithelial-adhesion transfer is independently supported in human epithelial cells.

Reason: The current mouse donor carries the term from PMID:33596089. That study also directly tests human intestinal epithelial DSC2 depletion, cell-sheet adhesion and junction assembly, in addition to conditional mouse experiments. The conserved structural adhesive participation is therefore corroborated on the human target rather than inferred solely from disease necessity.

Summary: DSC2 supports intestinal epithelial cell-cell adhesion and desmosome assembly.

Reason: Human SK-CO15/Caco-2 BBE depletion experiments and conditional mouse intestinal studies measure adhesion/barrier phenotypes and delayed desmoglein-2 recruitment after calcium switching. DSC2 supplies a desmosomal adhesive component, so its contribution is structural participation in epithelial adhesion, not an autonomous enzymatic activity. The tension-sensor experiment uses DSG2 and is not relabeled as a DSC2 force measurement.

Summary: The conserved epithelial-repair phenotype is supported but is a contextual outcome of the adhesive system.

Reason: The mouse donor’s PMID:31967937 experiments include conditional intestinal deletion and wound repair, while human intestinal-cell experiments independently support migration and traction effects. Retain positive regulation of wound healing as a secondary tissue context; the work does not establish DSC2 as a Rap1 exchange factor or prove direct DSC2–integrin binding.

Summary: DSC2 promotes intestinal epithelial repair in the tested systems.

Reason: The source combines human intestinal-cell depletion/migration/traction assays with mouse intestinal wound-repair experiments. These positive results support the annotation as a tissue-level consequence of DSC2-dependent epithelial organization. Reduced integrins, plakophilin-3 and Rap1-GTP do not by themselves demonstrate a separate direct receptor, GEF or catalytic signaling mechanism.

Summary: The ancestral cell-cell adhesion function is supported across DSC2 tissue contexts.

Reason: The exact target descends from PTN001931974, which carries the literal cell-cell adhesion IBD. Target ectodomain binding, cardiac adhesion and intestinal epithelial experiments independently corroborate the inherited function. This cross-tissue process is an appropriate integrated core description; existing cardiac and epithelial terms preserve finer contexts without making the general adhesive mechanism false or requiring one tissue to substitute for the other. The target’s presence among source descendants is legitimate.

Summary: The ventricular-myocyte action-potential regulation claim requires more specific source evidence.

Reason: Clinical ECG/conduction findings and junctional protein phenotypes in the recovered source do not resolve the specific regulation of ventricular cardiac muscle cell action potentials. The full supplementary material remains unavailable. Preserve the positive IMP annotation and its source identity without asserting that the complete experiments lack such measurements or transferring a connexin-channel activity to DSC2.

Summary: The transferred p38MAPK-regulation claim has unresolved target-specific source scope.

Reason: The mouse Dsc2 donor P55292 carries the positive regulation term from PMID:26763450. The recovered main original’s operative Figure 6 and immunoprecipitation Methods describe Dsc3 in Dsg3-manipulated keratinocytes; historical DSC3 naming for human DSC2 is not sufficient to identify these experimental reagents. The supplement is unavailable, so the donor assertion is retained as unresolved rather than called a paralog miscitation or evidence of no DSC2 function.

Summary: The DSC2-specific positive p38MAPK-regulation assertion cannot yet be confirmed from the recovered original.

Reason: The accessed human HaCaT and mouse Dsg3-perturbation main-text experiments identify Dsc3-associated p38MAPK in Figure 6 and the stated IP reagent. They do not independently authenticate a DSC2-specific experiment in the inaccessible supplement. Preserve the experimental source annotation; no REMOVE or wrong-gene claim follows from the partial original scope, and an indirect intestinal Rap1 phenotype does not resolve the p38 claim.

Summary: DSC2 promotes timely recruitment of DSG2 to cell-cell junctions.

Reason: In human intestinal epithelial calcium-switch experiments, DSC2 depletion delays DSG2 recruitment to intercellular contacts while E-cadherin recruitment is preserved. The observed positive effect is specifically protein localization to a cell-cell junction, fitting GO:0150107, an is_a descendant of GO:1903829. This is source-supported junctional organization, not a claim that DSC2 transports every cargo or is the kinase responsible for desmoplakin phosphorylation.

Proposed replacements: positive regulation of protein localization to cell-cell junction