Desmoglein-2 is a single-pass desmosomal cadherin that supports adhesion in epithelial tissues and heart muscle. Its calcium-binding extracellular cadherin domains engage neighboring cells, and its cytoplasmic region connects to the desmosomal plaque. This transmembrane connection couples extracellular adhesion to the intracellular junctional architecture and helps tissues resist mechanical stress. Its extracellular region also serves as an attachment receptor for selected species B adenoviruses, including types 3, 7, 11 and 14/14a, and supports type 3 entry into human cells. DSG2 also occurs at non-desmosomal cell contacts and surface pools in progenitor, endothelial and pancreatic cells. Its junctional and signalling-associated roles vary with cell context; proteolytic cleavage can release extracellular or intracellular fragments. Human DSG2 variants are associated with arrhythmogenic cardiomyopathy and altered desmosomal structure.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001533 cornified envelope | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: The cornified-envelope assignment is a contextual propagated localization. Reason: The current ARBA00028309 rule has two target-matching condition sets. Independently, Reactome contains an explicit human DSG2 entity (R-HSA-8847737, Q14126 residues 50β1118) in cornified envelope, reached through the mature-envelope desmosomal component set. This is a positive curated model assignment, not an independently reconstructed DSG2-specific corneocyte experiment. Retain the contextual location as non-core: restriction to a particular tissue does not by itself contradict a cellular-component annotation, and the saved evidence does not establish that this target-specific model entity is erroneous. Supporting Evidence: GO_REF:0000117 Reactome:R-HSA-6814764 |
| GO:0001533 cornified envelope | TAS Reactome:R-HSA-6814764 | KEEP AS NON CORE | Summary: Reactome places DSG2 within the mature cornified-envelope model. Reason: The saved component path from the mature-envelope complex R-HSA-8847742 reaches the explicit human DSG2 entity R-HSA-8847737 (Q14126 residues 50β1118, cornified envelope) through the desmosome network and desmoglein set. This supports a curated, contextual compartment assertion, not direct target-specific measurement in corneocytes. Retain it as non-core with that model-evidence limitation; pathway membership alone would be insufficient, but this record explicitly assigns the target compartment. The cellular-component term does not require DSG2 to catalyse cornification. Supporting Evidence: Reactome:R-HSA-6814764 |
| GO:0002159 desmosome assembly | IEA GO_REF:0000107 | ACCEPT | Summary: DSG2 contributes the adhesive structural component of desmosome assembly. Reason: The literal mouse donor is O55111. Its curated experimental assembly records include PMID:19635863 and PMID:26085008. The former retains morphologically normal desmosomes despite conduction disease and must not be described as an assembly-loss experiment; the latter reports loss of desmosome-like structures after cardiomyocyte-specific depletion. Human ectodomain adhesion and plaque associations independently explain the structural work supplied by DSG2. Accept conserved assembly participation without attributing a catalytic assembly activity or making necessity alone the rationale. |
| GO:0002159 desmosome assembly | ISS GO_REF:0000024 | ACCEPT | Summary: DSG2 contributes the adhesive structural component of desmosome assembly. Reason: The literal mouse donor is O55111. Its curated experimental assembly records include PMID:19635863 and PMID:26085008. The former retains morphologically normal desmosomes despite conduction disease and must not be described as an assembly-loss experiment; the latter reports loss of desmosome-like structures after cardiomyocyte-specific depletion. Human ectodomain adhesion and plaque associations independently explain the structural work supplied by DSG2. Accept conserved assembly participation without attributing a catalytic assembly activity or making necessity alone the rationale. |
| GO:0002934 desmosome organization | IMP PMID:16505173 Mutations in desmoglein-2 gene are associated with arrhythmo... | ACCEPT | Summary: Human DSG2 disease-associated ultrastructure supports desmosome organization. Reason: The accessible PMID:16505173 abstract reports fewer desmosomes and wider intercellular gaps in biopsies from three mutation carriers. The complete operative experiments remain unavailable, so their details are not reconstructed. The broad organization term accommodates arrangement and stability as well as assembly; independent human adhesion and junction studies support that biological role. Do not replace all organization with a uniquely demonstrated assembly or disassembly step. |
| GO:0003165 Purkinje myocyte development | IMP PMID:16505173 Mutations in desmoglein-2 gene are associated with arrhythmo... | UNDECIDED | Summary: The Purkinje-development specificity remains unresolved. Reason: The current definition concerns progression of a Purkinje myocyte to its mature structure. The accessible PMID:16505173 abstract establishes human ARVC variants and desmosomal abnormalities, but does not resolve a Purkinje developmental assay. Full operative evidence was not recovered after bounded access attempts. Preserve the experimental assertion and defer judgment; disease or conduction defects alone do not establish this specific developmental process. Supporting Evidence: |
| GO:0005509 calcium ion binding | IBA GO_REF:0000033 | ACCEPT | Summary: Calcium binding is a conserved component of the cadherin adhesive mechanism. Reason: The literal IBD at PANTHER:PTN001931974 lies on the reconstructed path to human Q14126/PTN002513169; the target MSA sequence matches all 1118 residues. Its calcium-binding donor assertions and the target cadherin domains support inherited calcium coordination. Human ectodomain adhesion measurements and calcium-sensitive junction assays corroborate the role. This does not require a separate calcium-only core. |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: The cadherin domain assignments support calcium-ion binding. Reason: The exact target has the imported IPR002126, IPR009122 and IPR015919 domain assignments. Calcium coordination stabilizes the cadherin ectodomain architecture used in adhesion, independently supported by the human ectodomain study. Retain this molecular subactivity within the integrated adhesive mechanism, without asserting calcium transport or signalling catalysis. |
| GO:0005515 protein binding | IPI PMID:11790773 Protein binding and functional characterization of plakophil... | MODIFY | Summary: The PKP2 association supports cytoskeletal-protein binding. Reason: The original distinguishes positive co-immunoprecipitation of expressed full-length human PKP2a with human DSG2 in COS cells, positive PKP2 head-domain two-hybrid binding, and negative full-length two-hybrid/native SCC9 capture under other conditions. GO:0008092 concerns binding a cytoskeletal protein component, not only a filament-forming polymer subunit. The verified partner is a desmosomal plaque protein; the current human Q99959 GO:0005882 ISS record traces to mouse Q9CQ73 IDA PMID:16917092. These positive curated assignments support its cytoskeletal classification, while the donor experiment remains unreconstructed. The raw located_in qualifier is preserved, not rewritten as part_of or used to claim polymerization. Retain the informative binding class with the original assay limits; neither a purified interface nor downstream physiological regulation is asserted. Proposed replacements: cytoskeletal protein binding |
| GO:0005515 protein binding | IPI PMID:21220045 A novel desmocollin-2 mutation reveals insights into the mol... | MODIFY | Summary: The DSC2 association is refined 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 literal IntAct pair is human Q14126βQ02487, EBI-6901957/IM-20978-13, anti-tag co-immunoprecipitation (MI:0007), physical association (MI:0915), in COS-1 host cells. Both reference-sequence ROGIDs reproduce from the official sequences; the experimental record retains the DSG2 GFP tag and DSC2 binding-region feature rather than equating the constructs with unmodified full-length products. The 2011 association is complemented by direct human DSC2βDSG2 ectodomain adhesive binding in PMID:27298358. Proposed replacements: cadherin binding |
| GO:0005515 protein binding | IPI PMID:27298358 Structural basis of adhesive binding by desmocollins and des... | MODIFY | Summary: Direct human DSC2βDSG2 adhesive binding supports the specific cadherin 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 source assays all seven human desmosomal-cadherin ectodomains with binding and bead-adhesion measurements. Strong Dsg:Dsc heterophilic interactions include DSG2βDSC2. The soluble/bead assay preference is not universal exclusion of homophilic interactions in other experimental contexts. Proposed replacements: cadherin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29849084 Mapping of Adenovirus of serotype 3 fibre interaction to des... | MODIFY | Summary: The viral-knob interaction belongs to the established virus-receptor activity. Reason: The study tests human DSG2 ectodomain fragments against adenovirus type 3 knob, defining the EC2/EC3 contribution and binding stoichiometry under its construct conditions. This binding assay alone is not labelled an entry experiment. Independent PMID:21151137 demonstrates human DSG2-dependent attachment and transduction, including gain in receptor-negative human U937 cells, so the target-level receptor refinement is justified. Do not infer that the human receptor result applies to mouse DSG2. Proposed replacements: virus receptor activity |
| GO:0005515 protein binding | IPI PMID:29910125 DSG2 Is a Functional Cell Surface Marker for Identification ... | MODIFY | Summary: The identified beta-catenin association supports beta-catenin binding. Reason: PMID:29910125 Figure 6F shows DSG2 immunoprecipitation with beta-catenin in the human pluripotent-cell system; the displayed panel contains input and IP lanes but no IgG control lane. Human perturbation, nuclear active beta-catenin and reporter experiments support the associated retention/signalling context. The class term names the measured partner and does not assert purified direct affinity, transcription-factor activity by DSG2, or an independently solved interface. Proposed replacements: beta-catenin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:30862836 CryoEM structure of adenovirus type 3 fibre with desmoglein ... | MODIFY | Summary: The structural viral interaction is refined to the independently established receptor activity. Reason: The human DSG2βadenovirus type 3 knob cryo-EM study resolves receptor engagement and one/two-receptor populations. RCSB 6QNT identifies human Q14126 and viral P04501; a modeled fragment is not treated as a sequence-authenticated full experimental insert. Independent human attachment/transduction gain and blocking evidence from PMID:21151137 establishes the receptor function beyond structural binding alone. Proposed replacements: virus receptor activity |
| GO:0005515 protein binding | IPI PMID:35922511 A physical wiring diagram for the human immune system. | MODIFY | Summary: The DSC2 pair is retained under 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 source network includes the DSG2βDSC2 affinity record. The quantitative entry derived from the earlier 2016 study is distinguished from newly performed 2022 experiments rather than counted as independent replication; direct human ectodomain adhesive binding is in that primary source. Proposed replacements: cadherin binding |
| GO:0005576 extracellular region | IDA PMID:34742300 Identification of Desmoglein-2 as a novel target of Helicoba... | KEEP AS NON CORE | Summary: The extracellular observation concerns a shed DSG2 fragment. Reason: Human gastric epithelial experiments and recombinant extracellular DSG2 assays show H. pylori HtrA-dependent release of an N-terminal fragment, with inactive-protease and bacterial deletion controls. This is positive extracellular localization of a processed product, not evidence of constitutive secretion of intact membrane DSG2. HtrA performs the proteolysis; no DSG2 protease or processing-process function is inferred. Supporting Evidence: |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The curated extracellular assignment is compatible with ectodomain shedding. Reason: The UniProt subcellular-location mapping is retained with the primary human shedding evidence. The released extracellular portion is distinguished from the membrane-retained precursor and from a secreted natural isoform. No unsupported exclusive soluble location or autonomous proteolytic activity is assigned. |
| GO:0005737 cytoplasm | IDA PMID:17559062 The most widespread desmosomal cadherin, desmoglein 2, is a ... | KEEP AS NON CORE | Summary: The cytoplasmic annotation retains a documented cytosolic processed-fragment context. Reason: Retain cytoplasm as a supported non-core location encompassing several intracellular DSG2 contexts. This source specifically reports a 70-kDa intracellular fragment released into the cytosol during staurosporine-induced apoptosis in human HaCaT and HT-29 cells, with caspase-inhibitor preservation of membrane labeling. That positive cytosolic observation remains valid; it does not establish that the intact protein or the diffuse progenitor-cell and disease-variant pools are all organelle-free. A single cytosol replacement would not represent this combined location claim. Full Methods for this source remain unavailable, and the fragment is not a new natural product. Supporting Evidence: |
| GO:0005737 cytoplasm | IDA PMID:27338829 A non-canonical role for desmoglein-2 in endothelial cells: ... | KEEP AS NON CORE | Summary: Human endothelial progenitors show a diffuse cytoplasmic DSG2 pool. Reason: The actual Results and Figure 1c describe DSG2 across the surface and cytoplasm of human endothelial progenitor cells, unlike punctate desmosomal staining in HaCaT controls. This evidence does not resolve the entire intracellular signal into cytosol or a specific organelle. Retain the broad positive cytoplasmic observation without imposing the location of a different processed-fragment assay. Supporting Evidence: |
| GO:0005737 cytoplasm | IDA PMID:38375917 Ser194Leu DSG2 mutation, associated with arrhythmogenic left... | KEEP AS NON CORE | Summary: The cytoplasmic observation is bounded by the disease-variant context. Reason: The accessible human S194L study reports perinuclear accumulation together with altered DSG2/CX43 distribution. Retain the imported positive localization with its variant context; do not convert it into an exclusive physiological wild-type perinuclear or soluble-cytosol assignment. Complete operative imaging and construct Methods remain unavailable. Supporting Evidence: |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The curated cytoplasmic location accommodates distinct intracellular pools. Reason: UniProt SL-0086 is compatible with the directly observed diffuse human progenitor-cell distribution and the separately released apoptotic intracellular fragment. The former is not resolved into an organelle-free cytosol, whereas the latter is explicitly cytosolic. Retain the broader combined location rather than replacing all source contexts with only the fragment compartment. |
| GO:0005886 plasma membrane | EXP PMID:27338829 A non-canonical role for desmoglein-2 in endothelial cells: ... | ACCEPT | Summary: Human progenitor and endothelial cells show DSG2 at the plasma membrane. Reason: Surface flow cytometry and imaging in the original human endothelial/progenitor-cell study establish a membrane pool, including non-desmosomal distribution. This source cannot be narrowed wholly to desmosome. The plasma-membrane location is compatible with the adhesive and virus-receptor mechanisms without implying that receptor activity was assayed here. Supporting Evidence: |
| GO:0005886 plasma membrane | EXP PMID:31402609 S-acylated Golga7b stabilises DHHC5 at the plasma membrane t... | ACCEPT | Summary: The palmitoylation study supports a plasma-membrane DSG2 pool. Reason: The accessible primary abstract identifies DSG2 as a DHHC5 substrate and reports its plasma-membrane/desmosomal distribution. Preserve the positive localization, corroborated independently in human cells. Full operative source Methods remain unavailable, so exact construct and palmitoylation-assay details are not invented. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: HPA independently supports plasma-membrane localization. Reason: The exact HPA ENSG00000046604/Q14126 page rates plasma membrane supported, separately from supported cell junctions and approved vesicles. HPA004896 records KOLF2.1J plasma-membrane/junction staining; A-431 has junction/vesicle observations. No pixel-based compartment conclusion is claimed and the overall gene score is not substituted for individual location reliability. Supporting Evidence: GO_REF:0000052 https://www.proteinatlas.org/ENSG00000046604-DSG2/subcellular |
| GO:0005886 plasma membrane | IDA PMID:17559062 The most widespread desmosomal cadherin, desmoglein 2, is a ... | ACCEPT | Summary: The apoptosis study observes membrane DSG2 before cleavage. Reason: The primary abstract reports loss of surface DSG2 staining during caspase-dependent processing and preservation of membrane labeling by the caspase-3 inhibitor. The membrane precursor and released intracellular fragment are distinct pools. Retain plasma membrane; no inference that every signal is exclusively desmosomal is required. Supporting Evidence: |
| GO:0005886 plasma membrane | IDA PMID:26918609 c-Src/Cav1-dependent activation of the EGFR by Dsg2. | ACCEPT | Summary: The epithelial signalling study supports a nonjunctional membrane pool. Reason: Human HaCaT/A431 and related cell experiments examine DSG2-dependent EGFR/c-Src/caveolin redistribution, including lipid-raft fractions. These observations establish membrane-associated DSG2 beyond a claim that all function occurs at desmosomes. They do not make DSG2 itself a kinase or establish one universal membrane microdomain. Supporting Evidence: |
| GO:0005886 plasma membrane | IDA PMID:30885746 In vitro analysis of arrhythmogenic cardiomyopathy associate... | ACCEPT | Summary: Glycosylation-sensitive surface localization supports plasma membrane. Reason: The imported experimental annotation positively asserts plasma-membrane localization. The accessible abstract measures wild-type/mutant DSG2 glycosylation patterns but does not itself reconstruct the localization assay. Independent human DSG2 surface measurements support the same location, so retain the curator assertion with the full source Methods/construct limit explicit. No enzymatic glycosylation activity is assigned to DSG2. |
| GO:0005886 plasma membrane | IDA PMID:36309486 Desmoglein-2 is important for islet function and Ξ²-cell surv... | ACCEPT | Summary: Human pancreatic-cell observations support surface DSG2. Reason: The full source separately shows human islet/body-donor staining and surface flow cytometry, while mouse hypomorphs and mouse beta-cell perturbations supply functional developmental/secretory evidence. Retain the human membrane observation without transferring the mouse perturbation to human cells or calling all pancreatic signal desmosomal. Supporting Evidence: |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: The domain and curated-location mappings support plasma membrane. Reason: The imported IPR020894/SL-0039 assignments agree with the target single-pass cadherin architecture and directly observed human surface pools. Preserve the broad membrane location because non-desmosomal progenitor and receptor-accessible pools are also established. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-351877 | ACCEPT | Summary: The Reactome event contains an exact human DSG2 plasma-membrane entity. Reason: The saved participant path 351877 β 351896 reaches R-HSA-351896, human Q14126 residues 50β1118 at GO:0005886. The event is Caspase-mediated cleavage of Desmoglein 2. DSG2 occurs as an input or as a component of the input complex, not as the enzyme carrying out the event. This source supports the membrane pool without making every contextual reaction a DSG2 catalytic or core process. Supporting Evidence: Reactome:R-HSA-351877 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6809393 | ACCEPT | Summary: The Reactome event contains an exact human DSG2 plasma-membrane entity. Reason: The saved participant path 6809393 β 6814388 β 6814694 β 351896 reaches R-HSA-351896, human Q14126 residues 50β1118 at GO:0005886. The event is Keratin filaments bind cell-cell adhesion complexes. DSG2 occurs as an input or as a component of the input complex, not as the enzyme carrying out the event. This source supports the membrane pool without making every contextual reaction a DSG2 catalytic or core process. Supporting Evidence: Reactome:R-HSA-6809393 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6810357 | ACCEPT | Summary: The Reactome event contains an exact human DSG2 plasma-membrane entity. Reason: The saved participant path 6810357 β 8942225 β 6814735 β 6814388 β 6814694 β 351896 reaches R-HSA-351896, human Q14126 residues 50β1118 at GO:0005886. The event is Fillagrin and keratin intermediate filaments polymerize forming a network. DSG2 occurs as an input or as a component of the input complex, not as the enzyme carrying out the event. This source supports the membrane pool without making every contextual reaction a DSG2 catalytic or core process. Supporting Evidence: Reactome:R-HSA-6810357 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6810937 | ACCEPT | Summary: The Reactome event contains an exact human DSG2 plasma-membrane entity. Reason: The saved participant path 6810937 β 6814285 β 6814323 β 8942225 β 6814735 β 6814388 β 6814694 β 351896 reaches R-HSA-351896, human Q14126 residues 50β1118 at GO:0005886. The event is Lamellar bodies bind the early cornified envelope. DSG2 occurs as an input or as a component of the input complex, not as the enzyme carrying out the event. This source supports the membrane pool without making every contextual reaction a DSG2 catalytic or core process. Supporting Evidence: Reactome:R-HSA-6810937 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6811539 | ACCEPT | Summary: The Reactome event contains an exact human DSG2 plasma-membrane entity. Reason: The saved participant path 6811539 β 6814323 β 8942225 β 6814735 β 6814388 β 6814694 β 351896 reaches R-HSA-351896, human Q14126 residues 50β1118 at GO:0005886. The event is Reinforcement of the Cornified Envelope. DSG2 occurs as an input or as a component of the input complex, not as the enzyme carrying out the event. This source supports the membrane pool without making every contextual reaction a DSG2 catalytic or core process. Supporting Evidence: Reactome:R-HSA-6811539 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6814298 | ACCEPT | Summary: The Reactome event contains an exact human DSG2 plasma-membrane entity. Reason: The saved participant path 6814298 β 6814723 β 6814278 β 6814285 β 6814323 β 8942225 β 6814735 β 6814388 β 6814694 β 351896 reaches R-HSA-351896, human Q14126 residues 50β1118 at GO:0005886. The event is Late envelope proteins bind cornified envelope:CDSN. DSG2 occurs as an input or as a component of the input complex, not as the enzyme carrying out the event. This source supports the membrane pool without making every contextual reaction a DSG2 catalytic or core process. Supporting Evidence: Reactome:R-HSA-6814298 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6814387 | ACCEPT | Summary: The Reactome event contains an exact human DSG2 plasma-membrane entity. Reason: The saved participant path 6814387 β 6814275 β 6814723 β 6814278 β 6814285 β 6814323 β 8942225 β 6814735 β 6814388 β 6814694 β 351896 reaches R-HSA-351896, human Q14126 residues 50β1118 at GO:0005886. The event is CASP14 cleaves filaggrin. DSG2 occurs as an input or as a component of the input complex, not as the enzyme carrying out the event. This source supports the membrane pool without making every contextual reaction a DSG2 catalytic or core process. Supporting Evidence: Reactome:R-HSA-6814387 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6814695 | ACCEPT | Summary: The Reactome event contains an exact human DSG2 plasma-membrane entity. Reason: The saved participant path 6814695 β 6814388 β 6814694 β 351896 reaches R-HSA-351896, human Q14126 residues 50β1118 at GO:0005886. The event is PERP binds desmosomes. DSG2 occurs as an input or as a component of the input complex, not as the enzyme carrying out the event. This source supports the membrane pool without making every contextual reaction a DSG2 catalytic or core process. Supporting Evidence: Reactome:R-HSA-6814695 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6814734 | ACCEPT | Summary: The Reactome event contains an exact human DSG2 plasma-membrane entity. Reason: The saved participant path 6814734 β 6814278 β 6814285 β 6814323 β 8942225 β 6814735 β 6814388 β 6814694 β 351896 reaches R-HSA-351896, human Q14126 residues 50β1118 at GO:0005886. The event is CDSN binds the cornified envelope. DSG2 occurs as an input or as a component of the input complex, not as the enzyme carrying out the event. This source supports the membrane pool without making every contextual reaction a DSG2 catalytic or core process. Supporting Evidence: Reactome:R-HSA-6814734 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6814764 | ACCEPT | Summary: The Reactome event contains an exact human DSG2 plasma-membrane entity. Reason: The saved participant path 6814764 β 6814763 β 6814757 β 6814758 β 6814759 β 6814760 β 6814735 β 6814388 β 6814694 β 351896 reaches R-HSA-351896, human Q14126 residues 50β1118 at GO:0005886. The event is Plasma membrane resorption. DSG2 occurs as an input or as a component of the input complex, not as the enzyme carrying out the event. This source supports the membrane pool without making every contextual reaction a DSG2 catalytic or core process. Supporting Evidence: Reactome:R-HSA-6814764 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8942224 | ACCEPT | Summary: The Reactome event contains an exact human DSG2 plasma-membrane entity. Reason: The saved participant path 8942224 β 6814735 β 6814388 β 6814694 β 351896 reaches R-HSA-351896, human Q14126 residues 50β1118 at GO:0005886. The event is Filaggrin binds Keratin tonofilament:Desmosome. DSG2 occurs as an input or as a component of the input complex, not as the enzyme carrying out the event. This source supports the membrane pool without making every contextual reaction a DSG2 catalytic or core process. Supporting Evidence: Reactome:R-HSA-8942224 |
| GO:0005911 cell-cell junction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: The junction assignment includes both desmosomal and non-desmosomal pools. Reason: Current ARBA00028427 retrieval did not reconstruct a target-matching condition set, which is a current-rule limit rather than proof that the historical mapping was false. Human desmosomes and non-desmosomal stem/progenitor junctions independently support cell-cell junction. Retain this broader source claim because replacing it only with desmosome would erase the latter experimentally supported context. |
| GO:0005911 cell-cell junction | TAS PMID:8143788 Identification of the ubiquitous human desmoglein, Dsg2, and... | KEEP AS NON CORE | Summary: The broad junction annotation retains desmosomal and non-desmosomal contexts. Reason: Retain cell-cell junction as a supported non-core location encompassing both desmosomal and independently observed non-desmosomal DSG2 contacts. This historical source specifically characterizes human and bovine DSG2 in desmosomal junctions; that precise localization remains supported by the eight accepted desmosome annotations and the adhesive core. Replacing the combined broad claim only with desmosome would omit the non-desmosomal stem/progenitor and endothelial contexts. The historical human precursor length is not silently equated with the modern 1118-residue sequence; complete original Methods remain unavailable. Supporting Evidence: |
| GO:0007155 cell adhesion | IDA PMID:17559062 The most widespread desmosomal cadherin, desmoglein 2, is a ... | MODIFY | Summary: The source concerns intercellular adhesion rather than cell adhesion in general. Reason: The primary abstract measures progressive loss of epithelial intercellular adhesion during DSG2 cleavage and inhibitor-associated preservation. Independent human cadherin ectodomain studies establish the adhesive interaction itself. Refine to cell-cell adhesion, without assigning DSG2 the caspase reaction that disrupts it. Proposed replacements: cell-cell adhesion |
| GO:0007155 cell adhesion | IEA GO_REF:0000002 | MODIFY | Summary: The cadherin domain mapping is refined to cell-cell adhesion. Reason: The target IPR020894 assignment and direct human ectodomain binding/adhesion experiments support adhesion between cells. This is more informative than the broad cell-adhesion parent and does not imply cell-matrix adhesion or one exclusive homo/heterophilic geometry. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR020894 SUPPORTS TRANSFER The authentic target domain mapping supports the broad source claim; independent target experiments justify the specified biological refinement without exclusive-compartment or unmeasured catalytic inference. Proposed replacements: cell-cell adhesion |
| GO:0007156 homophilic cell-cell adhesion | IDA PMID:17559062 The most widespread desmosomal cadherin, desmoglein 2, is a ... | ACCEPT | Summary: Homophilic adhesion is supported in a bounded assay context. Reason: Retain the experimental assertion; the original apoptosis paper is abstract-only and its exact homophilic assay is not reconstructed. Independent PMID:25213555 measures human DSG2 homophilic AFM interactions, whereas PMID:27298358 finds much stronger heterophilic interactions in soluble/bead assays. These context-dependent observations do not justify deleting the homophilic function or claiming it is the exclusive physiological adhesive mode. PMID:29999492 separately reports DSG2 homophilic AFM events at background, with positive DSG2βDSC2 heterophilic binding. This assay disagreement remains explicit rather than being averaged into a universal binding preference. |
| GO:0007156 homophilic cell-cell adhesion | IEA GO_REF:0000002 | ACCEPT | Summary: The homophilic cadherin inference has independent target support. Reason: A cadherin-domain assignment alone would not establish that every desmosomal interaction is homophilic. Here the human DSG2 AFM source provides positive homophilic evidence, with the later soluble/bead heterophilic preference preserved as a distinct assay result. Retain the molecularly grounded adhesion mode without universalizing it. PMID:29999492 separately reports DSG2 homophilic AFM events at background, with positive DSG2βDSC2 heterophilic binding. This assay disagreement remains explicit rather than being averaged into a universal binding preference. |
| GO:0009986 cell surface | HDA PMID:19581412 Quantitative proteomics identifies a Dab2/integrin module re... | KEEP AS NON CORE | Summary: The high-throughput surface assignment is retained with its record-level limit. Reason: The full paper establishes HeLa surface-glycoprotein capture with membrane-impermeant labeling, SILAC and glycopeptide mass spectrometry. The exact DSG2 table/peptide entry was not independently recovered, and the integrin-focused follow-up is not relabeled as DSG2 validation. Independent human DSG2 surface measurements make the positive location credible; retain the curator HDA assertion as non-core rather than call it a wrong-gene annotation. |
| GO:0009986 cell surface | IDA PMID:27338829 A non-canonical role for desmoglein-2 in endothelial cells: ... | KEEP AS NON CORE | Summary: Human endothelial progenitor-cell assays directly support cell-surface exposure. Reason: Surface flow cytometry and imaging directly detect DSG2 on human endothelial progenitor cells, with diffuse non-desmosomal distribution. Retain cell surface as the assay-specific anatomical assertion. Plasma membrane is not a typed descendant of cell surface, and the separately accepted plasma-membrane observation does not replace the information about external accessibility recorded here. Supporting Evidence: |
| GO:0010719 negative regulation of epithelial to mesenchymal transition | IMP PMID:29910125 DSG2 Is a Functional Cell Surface Marker for Identification ... | KEEP AS NON CORE | Summary: The human pluripotent-cell study supports contextual suppression of EMT. Reason: Human DSG2 depletion, epithelial/mesenchymal marker changes, nuclear active beta-catenin, TCF/LEF reporter and Slug experiments support this signed regulatory outcome. The phenotype is accompanied by a plausible junctional beta-catenin retention mechanism, not merely expression correlation. Keep it as a context-dependent role without making DSG2 a transcription factor or adding a new process row. Supporting Evidence: |
| GO:0014704 intercalated disc | IDA PMID:23381804 Mutated desmoglein-2 proteins are incorporated into desmosom... | KEEP AS NON CORE | Summary: The cardiac junction location is retained with bounded original access. Reason: The accessible source reports human endomyocardial-biopsy immunohistochemistry and incorporation of wild-type/mutant DSG2 into desmosomes. Full spatial imaging details remain unavailable. Independent human heart and mouse studies support the intercalated-disc pool, so retain the positive anatomical assignment without asserting that the entire disc is a single desmosome. |
| GO:0014704 intercalated disc | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse donor supports conserved intercalated-disc localization. Reason: The exact donor is mouse O55111. The operative mouse transgenic study places FLAG-tagged mouse Dsg2 at intercalated discs; its cDNA was amplified from FVB/N cardiac tissue, not human cells. Human cardiac observations independently corroborate the location. Retain the anatomical compartment as a contextual pool rather than transfer every mutant phenotype or equate the whole disc with desmosome. |
| GO:0014704 intercalated disc | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The mouse donor supports conserved intercalated-disc localization. Reason: The exact donor is mouse O55111. The operative mouse transgenic study places FLAG-tagged mouse Dsg2 at intercalated discs; its cDNA was amplified from FVB/N cardiac tissue, not human cells. Human cardiac observations independently corroborate the location. Retain the anatomical compartment as a contextual pool rather than transfer every mutant phenotype or equate the whole disc with desmosome. |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: The membrane assignment is specified by documented membrane and junction locations. Reason: The authentic InterPro signatures support the broad membrane assignment. Independent human junction/adhesion studies establish desmosomal placement, while surface assays and HPA support plasma membrane. These are nonexclusive biological replacements, not a claim that desmosome is an is_a/part_of descendant of membrane. HPA also reports an approved whole-vesicle observation in A-431 cells; that positive observation remains in the source findings and notes, but it does not resolve vesicle-membrane versus luminal topology and is not used as a replacement for this membrane annotation. No endosome, ER, trafficking route or additional localization row is inferred. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR002126 SUPPORTS TRANSFER The authentic target-domain mapping supports the broad membrane claim. Independent human evidence supplies the named membrane/junction locations; whole-vesicle staining does not resolve vesicle-membrane topology. InterPro:IPR009122 SUPPORTS TRANSFER The authentic target-domain mapping supports the broad membrane claim. Independent human evidence supplies the named membrane/junction locations; whole-vesicle staining does not resolve vesicle-membrane topology. InterPro:IPR015919 SUPPORTS TRANSFER The authentic target-domain mapping supports the broad membrane claim. Independent human evidence supplies the named membrane/junction locations; whole-vesicle staining does not resolve vesicle-membrane topology. Proposed replacements: desmosome plasma membrane Supporting Evidence: GO_REF:0000002 https://www.proteinatlas.org/ENSG00000046604-DSG2/subcellular |
| GO:0030054 cell junction | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA supports junctional staining without resolving every junction to desmosome. Reason: The target HPA page rates cell junctions supported. HPA004896 records A-431 and KOLF2.1J junctions, and CAB025122 records A-431 junctions. The stem-cell/non-desmosomal context cautions against assigning all HPA junction signal to desmosomes. Preserve the source resolution while the direct desmosome rows retain the finer established adhesive pool. Supporting Evidence: GO_REF:0000052 https://www.proteinatlas.org/ENSG00000046604-DSG2/subcellular |
| GO:0030057 desmosome | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT desmosome annotation is supported by the target clade and direct evidence. Reason: The literal IBD at PANTHER:PTN002771392 is on the reconstructed human Q14126 lineage, and its descendant evidence includes the target itself. That is legitimate experimental grounding, not circularity. The target MSA sequence is exact and multiple human studies establish desmosomal localization; no target-specific loss or clade-exclusion evidence argues against the curator node. |
| GO:0030057 desmosome | IDA PMID:20859650 E-cadherin and plakoglobin recruit plakophilin3 to the cell ... | ACCEPT | Summary: Human epithelial DSG2 is observed in the desmosomal junctional pool. Reason: The actual Results show DSG2 border staining in human HaCaT and HCT116 controls and depletion from borders after PKP3 knockdown. The source distinguishes DSG2 from its DSC2/3 cross-reactive antibody; the latter caveat is not transferred to the DSG2 measurement. These data support the location and context-dependent recruitment without assigning PKP3 perturbation itself to a DSG2 enzyme activity. Supporting Evidence: |
| GO:0030057 desmosome | IDA PMID:23381804 Mutated desmoglein-2 proteins are incorporated into desmosom... | ACCEPT | Summary: The human disease study supports incorporation of DSG2 into desmosomes. Reason: The accessible abstract explicitly reports endomyocardial/epidermal immunohistochemistry, wild-type and mutant protein expression, and normal desmosomal incorporation. Retain the curator location; limited access does not support a misattribution claim. The exact assays for more specific electrical annotations from this paper remain separately unresolved. Supporting Evidence: |
| GO:0030057 desmosome | IDA PMID:29999492 E-cadherin binds to desmoglein to facilitate desmosome assem... | ACCEPT | Summary: Human keratinocyte imaging places DSG2 in nascent desmosomes. Reason: The actual structured-illumination microscopy Results identify DSG2 at nascent human keratinocyte desmosomes, using the paired desmoplakin pattern to locate the junctions during calcium-induced assembly. This localization evidence is separate from the AFM assay, in which DSG2 homophilic events were at background while DSG2βDSC2 heterophilic binding was positive. Retain the demonstrated desmosome location without transferring DSC2 homophilic results to DSG2 or making every DSG2 pool junction-bound. |
| GO:0030057 desmosome | IDA PMID:31845994 Desmoglein-2 mutations in propeptide cleavage-site causes ar... | ACCEPT | Summary: Human heart and cell-model observations support desmosomal incorporation. Reason: The source examines human heart and wild-type/propeptide-cleavage-site mutant DSG2-GFP constructs. Mutations can prevent propeptide processing without abolishing junction targeting, while stress alters incorporation and internalization. Retain desmosome localization, distinguishing processed precursor status from a naturally alternative isoform or DSG2 protease activity. Supporting Evidence: |
| GO:0030057 desmosome | IDA PMID:33596089 Regulation of intestinal epithelial intercellular adhesion a... | ACCEPT | Summary: The primary junction study supports desmosomal DSG2. Reason: The original uses human SKCO-15 intestinal epithelial cells and a calcium-switch assay: DSC2 depletion delays DSG2 recruitment to the plasma membrane during junction assembly. Its engineered human DSG2 tension sensor contains an inserted FRET module between Gly762 and Ala763 and reports load in the desmosomal context. Retain the direct compartment observation, distinguishing this engineered sensor from the natural product and mechanical load from an autonomous mechanosensor or signalling enzyme. |
| GO:0030057 desmosome | IDA PMID:38375917 Ser194Leu DSG2 mutation, associated with arrhythmogenic left... | ACCEPT | Summary: The variant study retains a desmosomal DSG2 pool. Reason: The accessible human S194L study reports altered DSG2/CX43 distribution and perinuclear accumulation; this does not negate the established desmosomal wild-type pool. Retain the positive curated desmosome assertion with the disease-variant distinction and incomplete operative imaging access, rather than infer exclusive cytoplasmic localization. |
| GO:0030057 desmosome | IEA GO_REF:0000120 | ACCEPT | Summary: The mouse and curated-location sources support desmosome. Reason: The imported mouse O55111 and UniProt SL-0092 sources agree with extensive human junction evidence. Mouse donor phenotypes are not represented as human experiments, and the positive target localization is independently established. Preserve this mapping rather than interpret coexisting nonjunctional pools as a contradiction. |
| GO:0031018 endocrine pancreas development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The endocrine-pancreas role is retained as an ortholog-supported context. Reason: The literal mouse donor is O55111, experimentally grounded by PMID:36309486. Whole-body Dsg2 hypomorphs have altered islet number/size, insulin secretion and pancreatic vascular features; mouse beta-cell perturbations are separate from human islet localization. These data support the existing context but do not establish a human developmental perturbation or a new autonomous endocrine mechanism. Preserve the imported transfer as non-core. |
| GO:0031018 endocrine pancreas development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The endocrine-pancreas role is retained as an ortholog-supported context. Reason: The literal mouse donor is O55111, experimentally grounded by PMID:36309486. Whole-body Dsg2 hypomorphs have altered islet number/size, insulin secretion and pancreatic vascular features; mouse beta-cell perturbations are separate from human islet localization. These data support the existing context but do not establish a human developmental perturbation or a new autonomous endocrine mechanism. Preserve the imported transfer as non-core. |
| GO:0032880 regulation of protein localization | IMP PMID:26918609 c-Src/Cav1-dependent activation of the EGFR by Dsg2. | KEEP AS NON CORE | Summary: DSG2 regulates the distribution of signalling-associated membrane proteins. Reason: The source measures DSG2-dependent EGFR/c-Src/caveolin redistribution and lipid-raft association in human epithelial/cancer cell systems. The broad localization-regulation claim accommodates these multiple cargo and compartment effects; a single uniformly signed or compartment-specific replacement is not established. Keep this context without assigning the catalytic activity of EGFR or Src to DSG2. Supporting Evidence: |
| GO:0042803 protein homodimerization activity | IEA GO_REF:0000107 | ACCEPT | Summary: DSG2 self-association is supported, with assay dependence preserved. Reason: The literal mouse O55111 donor has an IDA homodimerization record from PMID:36268721. Its recovered main text and Figure 1 caption measure homotypic wild-type DSG2 extracellular-domainβFc binding, reduced to background by W2A, and separately test human CaCo2 and mouse keratinocyte adhesion. Expanded construct Methods were not recovered, so the species of the AFM DSG2 insert is not inferred from the human Fc tag or mouse donor record. Independent explicitly human DSG2 AFM evidence from PMID:25213555 supports the target claim, with the contrary homophilic AFM result in PMID:29999492 retained as assay dependence. Accept the transfer without claiming an exclusive physiological homophilic mode. |
| GO:0042803 protein homodimerization activity | ISS GO_REF:0000024 | ACCEPT | Summary: DSG2 self-association is supported, with assay dependence preserved. Reason: The literal mouse O55111 donor has an IDA homodimerization record from PMID:36268721. Its recovered main text and Figure 1 caption measure homotypic wild-type DSG2 extracellular-domainβFc binding, reduced to background by W2A, and separately test human CaCo2 and mouse keratinocyte adhesion. Expanded construct Methods were not recovered, so the species of the AFM DSG2 insert is not inferred from the human Fc tag or mouse donor record. Independent explicitly human DSG2 AFM evidence from PMID:25213555 supports the target claim, with the contrary homophilic AFM result in PMID:29999492 retained as assay dependence. Accept the transfer without claiming an exclusive physiological homophilic mode. |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse donor supports protection against injury-associated apoptosis. Reason: Mouse O55111 is experimentally annotated from the kidney study. Tubular epithelial Dsg2 deletion increases apoptosis after several injury challenges, whereas unchallenged mice develop normally. Human HK-2 knockdown increases cell death separately. Retain the context-dependent protective role; do not generalize it to every tissue or to the pro-apoptotic effect of all cleaved DSG2 fragments. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:38395410 The role of desmoglein-2 in kidney disease. | KEEP AS NON CORE | Summary: The kidney study supports an injury-dependent protective outcome. Reason: The accessible source distinguishes increased apoptosis in injured mouse tubular epithelial Dsg2 knockouts from increased death after human HK-2 siRNA. Preserve the curated human process assertion with this cross-species and access boundary. The study does not establish a universal anti-apoptotic molecular activity or an additional core mechanism. Supporting Evidence: |
| GO:0045602 negative regulation of endothelial cell differentiation | IMP PMID:27338829 A non-canonical role for desmoglein-2 in endothelial cells: ... | UNDECIDED | Summary: The specific inhibition of endothelial differentiation remains unresolved. Reason: The original contains human stem/progenitor marker distributions, expression changes with lineage commitment, and endothelial tube/elongation and junctional-actin experiments. Those are genuine positive observations, but they do not clearly resolve which DSG2-dependent step actively reduces endothelial differentiation as defined by GO:0045602. Retain the curator assertion pending that mechanistic interpretation rather than call expression correlation proof of inhibition or declare the full annotation false. Supporting Evidence: |
| GO:0045785 positive regulation of cell adhesion | IMP PMID:38395410 The role of desmoglein-2 in kidney disease. | MODIFY | Summary: The supported adhesion effect is specifically between cells. Reason: The accessible kidney-study abstract explicitly states that DSG2 siRNA weakens cell-cell adhesion in human HK-2 cells. Refine the broad positive-regulation-of-cell-adhesion term to its cell-cell descendant, retaining the experimental context and limited full-text access. This existing refinement is not a newly inferred process from disease necessity alone. Proposed replacements: positive regulation of cell-cell adhesion Supporting Evidence: |
| GO:0046983 protein dimerization activity | IDA PMID:31845994 Desmoglein-2 mutations in propeptide cleavage-site causes ar... | MODIFY | Summary: The dimerization activity is refined to DSG2 self-association. Reason: The curated source reports DSG2 homodimers and examines propeptide/EC1-dependent interactions, including human heart and engineered wild-type/variant constructs. Independent human DSG2 homophilic AFM evidence corroborates self-association. The refinement names the same-protein dimer rather than all heterophilic adhesive contacts, and does not turn the pathogenic constructs into natural products. Proposed replacements: protein homodimerization activity |
| GO:0050839 cell adhesion molecule binding | IPI PMID:17559062 The most widespread desmosomal cadherin, desmoglein 2, is a ... | MODIFY | Summary: The original plakoglobin association supports gamma-catenin binding. Reason: The exact imported IPI record names P14923/JUP as its partner. Current UniProt identifies that human protein as junction plakoglobin/catenin gamma, and GO:0045295 explicitly names binding to that subunit. The accessible PMID:17559062 abstract reports plakoglobin cleavage and detachment from DSG2 during staurosporine-induced apoptosis in HaCaT and HT-29 cells. Refine the existing positive pair to gamma-catenin binding; do not substitute the independently established DSC2 interaction. Full operative binding Methods remain unavailable, so no purified affinity, direct interface, stoichiometry or unmodified full-length construct is claimed. Proposed replacements: gamma-catenin binding Supporting Evidence: |
| GO:0060231 mesenchymal to epithelial transition | IMP PMID:29910125 DSG2 Is a Functional Cell Surface Marker for Identification ... | KEEP AS NON CORE | Summary: DSG2 contributes to a contextual mesenchymal-to-epithelial transition. Reason: Human fibroblast reprogramming, epithelial/mesenchymal markers and beta-catenin/Slug pathway measurements provide direct context for this existing process assertion. The structural adhesion and beta-catenin association give a plausible performed contribution, while not establishing that every DSG2-expressing cell undergoes MET or that DSG2 catalyses transcription. Retain as non-core. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: The original positively identifies DSG2 in human parotid-saliva exosome preparations. Reason: The original Discussion explicitly names DSG2 among the human parotid-saliva exosome proteins, and the recovered Supplementary Table 2, sheet Paratid Exosomes, row 76 identifies DSG2/desmoglein 2 preproprotein (IPI00028931.2; 1118 residues), with sequence count 2, spectrum count 2 and sequence coverage 0.044. These measured columns establish target-specific proteomic detection; the adjacent biological-function and localization descriptions are background annotations, not additional experiments. Retain the HDA compartment as non-core. The peptide sequences and DSG2-specific orthogonal validation were not independently reconstructed, and the detection does not establish intact-protein topology or an exosome-biogenesis function. Supporting Evidence: |
| GO:0072089 stem cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Stem-cell proliferation is an ortholog-supported developmental context. Reason: The literal donor is mouse O55111. PMID:12494996 reports that Dsg2 loss impairs mouse ES-cell proliferation and early embryo survival, with DSG2 at non-desmosomal junctions; its abstract is available but full Methods are not. Independent human pluripotent-cell perturbations in PMID:29910125 corroborate a related context. Retain the imported function as non-core without presenting mouse knockout as a human assay. |
| GO:0072089 stem cell proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Stem-cell proliferation is an ortholog-supported developmental context. Reason: The literal donor is mouse O55111. PMID:12494996 reports that Dsg2 loss impairs mouse ES-cell proliferation and early embryo survival, with DSG2 at non-desmosomal junctions; its abstract is available but full Methods are not. Independent human pluripotent-cell perturbations in PMID:29910125 corroborate a related context. Retain the imported function as non-core without presenting mouse knockout as a human assay. |
| GO:0086073 bundle of His cell-Purkinje myocyte adhesion involved in cell communication | IMP PMID:16505173 Mutations in desmoglein-2 gene are associated with arrhythmo... | UNDECIDED | Summary: The specified HisβPurkinje adhesion process is not independently resolved. Reason: This term requires adhesion between the named cardiac cell types as part of their communication. Human ARVC and desmosomal ultrastructure from the accessible source support cardiac adhesion generally, but the complete cell-type-specific experiment was not recovered. Preserve the experimental assertion without substituting general cardiomyopathy for the narrowly defined event. Supporting Evidence: |
| GO:0086083 cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication | IC PMID:16505173 Mutations in desmoglein-2 gene are associated with arrhythmo... | UNDECIDED | Summary: The cell-type-specific adhesive binding inference remains unresolved. Reason: The current definition is binding that connects a bundle-of-His cell with a Purkinje myocyte and contributes to communication. General cadherin adhesion is established, but the imported IC assertion adds a particular cellular interface that cannot be reconstructed from the accessible PMID:16505173 material. Do not silently equate it with all DSG2 adhesive interactions or remove it from abstract silence. Supporting Evidence: |
| GO:0086091 regulation of heart rate by cardiac conduction | IMP PMID:16505173 Mutations in desmoglein-2 gene are associated with arrhythmo... | UNDECIDED | Summary: The specific heart-rate regulation claim needs the full operative evidence. Reason: The term describes modulation of contraction frequency through cardiac conduction. Available clinical/abstract evidence establishes arrhythmogenic disease and desmosomal abnormalities, while independent mouse experiments establish conduction changes; none of that alone identifies the particular source-specific heart-rate-regulating step. The cited original operative electrophysiology was not recovered, so retain uncertainty rather than infer a direct pacemaker activity or dismiss the curator assertion. Supporting Evidence: |
| GO:0086091 regulation of heart rate by cardiac conduction | IMP PMID:23381804 Mutated desmoglein-2 proteins are incorporated into desmosom... | UNDECIDED | Summary: The specific heart-rate regulation claim needs the full operative evidence. Reason: The term describes modulation of contraction frequency through cardiac conduction. Available clinical/abstract evidence establishes arrhythmogenic disease and desmosomal abnormalities, while independent mouse experiments establish conduction changes; none of that alone identifies the particular source-specific heart-rate-regulating step. The cited original operative electrophysiology was not recovered, so retain uncertainty rather than infer a direct pacemaker activity or dismiss the curator assertion. Supporting Evidence: |
| GO:0098609 cell-cell adhesion | IBA GO_REF:0000033 | ACCEPT | Summary: Cell-cell adhesion is the conserved directly performed DSG2 role. Reason: The literal PAINT IBD at PANTHER:PTN001931974 lies on the verified target lineage. Human Q14126 appears among its descendant evidence, legitimately grounding the inference rather than creating circularity. Direct human ectodomain adhesive interactions and cellular junction observations support the inherited role. Both homo- and heterophilic assay contexts are retained. |
| GO:0098609 cell-cell adhesion | IEA GO_REF:0000107 | ACCEPT | Summary: The mouse transfer agrees with direct human cell-cell adhesion. Reason: The imported mouse O55111 source is supported by direct donor annotations and independently by human DSG2 ectodomain and cellular adhesion experiments. The target itself contributes the adhesive interaction; this is not merely downstream necessity. Retain the established process while preserving source species and assay boundaries. |
| GO:0098911 regulation of ventricular cardiac muscle cell action potential | IMP PMID:16505173 Mutations in desmoglein-2 gene are associated with arrhythmo... | UNDECIDED | Summary: The ventricular action-potential regulatory specificity is unresolved. Reason: The current term requires modulation of ventricular-myocyte action-potential creation, propagation or termination. Clinical arrhythmia and general conduction abnormalities are not automatically the full source-specific cellular assay. Operative electrophysiology from the cited original remains unavailable, so preserve the annotation pending verification rather than assert DSG2 is an ion channel or that the reported experiment never occurred. Supporting Evidence: |
| GO:0098911 regulation of ventricular cardiac muscle cell action potential | IMP PMID:23381804 Mutated desmoglein-2 proteins are incorporated into desmosom... | UNDECIDED | Summary: The ventricular action-potential regulatory specificity is unresolved. Reason: The current term requires modulation of ventricular-myocyte action-potential creation, propagation or termination. Clinical arrhythmia and general conduction abnormalities are not automatically the full source-specific cellular assay. Operative electrophysiology from the cited original remains unavailable, so preserve the annotation pending verification rather than assert DSG2 is an ion channel or that the reported experiment never occurred. Supporting Evidence: |
| GO:0106015 negative regulation of inflammatory response to wounding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse kidney injury context supports reduced inflammatory response. Reason: The literal donor O55111 has the experimental kidney-injury annotation. Conditional tubular epithelial deletion increases inflammation after injury, with normal baseline development. Preserve this context-dependent protective consequence as an existing non-core transfer; no universal anti-inflammatory activity or additional process assertion is introduced. |
| GO:0150107 positive regulation of protein localization to cell-cell junction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The donor supports junctional organization of other proteins in an endothelial context. Reason: The imported mouse ortholog assignment is retained with the literal donor record. Independent human endothelial DSG2 knockdown experiments show altered cortical actin and VE-cadherin/junction-associated organization. The donor and target assays are not conflated, and the evidence does not establish a general protein-transport motor. |
| GO:0150107 positive regulation of protein localization to cell-cell junction | IMP PMID:27338829 A non-canonical role for desmoglein-2 in endothelial cells: ... | KEEP AS NON CORE | Summary: Human endothelial perturbation supports junction-associated protein organization. Reason: The actual source uses three DSG2 siRNAs in human bone-marrow-derived endothelial cells, with reduced tube formation/elongation and redistribution of cortical actin and VE-cadherin-defined boundaries. Retain the existing positive junction-localization regulation in this context, without claiming that every affected cytoskeletal protein directly binds DSG2 or that it transports cargo autonomously. Supporting Evidence: |
| GO:1902459 positive regulation of stem cell population maintenance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Stem-cell population maintenance is retained as a contextual conserved role. Reason: The mouse O55111 donor is experimentally grounded by PMID:12494996, with mouse ES-cell and embryo survival/proliferation findings. Human DSG2 depletion/reprogramming in PMID:29910125 adds target-specific support for maintenance of pluripotent populations through adhesion/beta-catenin-associated effects. Keep the existing transfer as non-core and do not infer all developmental lineages or a new molecular activity. |
| GO:1902459 positive regulation of stem cell population maintenance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Stem-cell population maintenance is retained as a contextual conserved role. Reason: The mouse O55111 donor is experimentally grounded by PMID:12494996, with mouse ES-cell and embryo survival/proliferation findings. Human DSG2 depletion/reprogramming in PMID:29910125 adds target-specific support for maintenance of pluripotent populations through adhesion/beta-catenin-associated effects. Keep the existing transfer as non-core and do not infer all developmental lineages or a new molecular activity. |
| GO:1903672 positive regulation of sprouting angiogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse donor supports a pro-sprouting vascular context. Reason: Mouse Dsg2 hypomorph aortic/vascular assays in PMID:27338829 provide the donor context, distinct from human endothelial knockdown and tube-formation experiments. Retain the existing transferred regulatory process as non-core. Neither donor phenotype nor surface-marker correlation is converted into a new universal differentiation mechanism. |
| GO:1903672 positive regulation of sprouting angiogenesis | IMP PMID:27338829 A non-canonical role for desmoglein-2 in endothelial cells: ... | KEEP AS NON CORE | Summary: The original supports a vascular sprouting/elongation context. Reason: The paper separates mouse hypomorph vascular sprouting from human endothelial DSG2 perturbation, where multiple siRNAs reduce tube formation and elongation and alter junction-associated actin. These support the existing positive vascular regulatory role with explicit organism/assay scope. No autonomous angiogenic enzymatic mechanism is assigned. Supporting Evidence: |
| GO:1903779 regulation of cardiac conduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse donor directly supports a cardiac-conduction context. Reason: Mouse Dsg2 perturbations have ECG and mapped conduction abnormalities in PMID:19635863, with the 2015 ablation study independently reporting conduction defects and altered connexin43 distribution. The 2009 mouse cDNA/transgene is explicitly mouse; human clinical findings are separate. Retain regulation of conduction as a contextual consequence of the cardiac adhesive system, without narrowing it to a specific human channel or heart-rate mechanism. |
| GO:1903779 regulation of cardiac conduction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The mouse donor directly supports a cardiac-conduction context. Reason: Mouse Dsg2 perturbations have ECG and mapped conduction abnormalities in PMID:19635863, with the 2015 ablation study independently reporting conduction defects and altered connexin43 distribution. The 2009 mouse cDNA/transgene is explicitly mouse; human clinical findings are separate. Retain regulation of conduction as a contextual consequence of the cardiac adhesive system, without narrowing it to a specific human channel or heart-rate mechanism. |
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Download this section (compressed HTML)Q: Which membrane organization, force geometry and calcium conditions explain the differing DSG2 homophilic results across AFM and solution/bead assays?
Q: Do the narrow HisβPurkinje, heart-rate and ventricular-action-potential annotations reflect directly measured DSG2-dependent steps, or the broader consequence of damaged cardiac adhesion?
Q: Does DSG2 actively inhibit endothelial differentiation, or do the reported lineage-marker changes primarily track cell state while DSG2 affects adhesion and vascular organization?
Q: Which molecular form of DSG2 is present in parotid exosomes and HPA-positive vesicles, and what functions, if any, accompany these contextual pools?
Experiment: Compare sequence-authenticated human DSG2 ectodomains and cell-surface constructs in matched homophilic/DSC2 heterophilic assays while varying calcium, force geometry and membrane density; measure binding and adhesion separately.
Experiment: Separate adhesion loss from electrophysiological changes in human cardiomyocyte conduction systems using matched rescue constructs, cell-type-resolved localization and direct action-potential/conduction measurements.
Experiment: Follow DSG2-positive vesicles and purified salivary extracellular vesicles with domain-specific antibodies and peptide mapping to distinguish intact receptor from shed or intracellular fragments.
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