Desmoplakin is a plakin-family structural protein that couples intracellular junctional plaques to intermediate-filament networks. Its N-terminal region engages plaque partners and its C-terminal tail binds filament proteins, organizing desmosomes and supporting the mechanical integrity of epithelial and cardiac tissues. Cytoplasmic assembly particles recruit desmoplakin to cell contacts, and cardiac pools also occupy mixed fascia-adherens-like junctions. Association with EB1 helps organize cortical microtubule ends and promotes connexin-43 localization to cell-cell junctions. Alternative splicing changes the central rod while retaining terminal interaction regions. Pathogenic DSP variants cause skin fragility, keratoderma and cardiomyopathy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000723 telomere maintenance | IMP PMID:31595153 Nuclear localization of Desmoplakin and its involvement in t... | KEEP AS NON CORE | Summary: Human HEK293 and other cultured-cell experiments in the recovered original show nuclear DSP, telomere-associated ChIP/FISH signals, TRF2 dependence, and altered telomere length and damage after DSP depletion, with rescue. Reason: Human HEK293 and other cultured-cell experiments in the recovered original show nuclear DSP, telomere-associated ChIP/FISH signals, TRF2 dependence, and altered telomere length and damage after DSP depletion, with rescue. These are positive contextual results. ChIP and co-immunoprecipitation do not establish purified DNA binding, an autonomous telomere enzyme, or a general replacement for the desmosomal structural role. The proposed nuclear-lamina mechanism remains a hypothesis. Supporting Evidence: |
| GO:0001533 cornified envelope | IDA PMID:10908733 Small proline-rich protein 1 is the major component of the c... | KEEP AS NON CORE | Summary: The original human oral-epithelial cornified-envelope preparation was exhaustively extracted with SDS and reducing agent before proteolysis and peptide sequencing. Reason: The original human oral-epithelial cornified-envelope preparation was exhaustively extracted with SDS and reducing agent before proteolysis and peptide sequencing. Its Table 2 identifies a DSP-derived peptide in the resistant envelope material. This is positive incorporation evidence, although the experiment did not isolate a DSP-containing covalent junction or measure an enzymatic activity of DSP. Retain the differentiated-envelope pool. Supporting Evidence: |
| GO:0001533 cornified envelope | TAS Reactome:R-HSA-6814764 | KEEP AS NON CORE | Summary: The exact Reactome output membership chain reaches human DSP/P15924, nominal residues 1–2871, in the cornified-envelope entity 8847736 through the nested envelope complexes. Reason: The exact Reactome output membership chain reaches human DSP/P15924, nominal residues 1–2871, in the cornified-envelope entity 8847736 through the nested envelope complexes. This agrees with the independently recovered human envelope peptide evidence. It represents a differentiated-envelope pool, not transglutaminase catalysis by DSP. Supporting Evidence: Reactome:R-HSA-6814764 file:human/DSP/DSP-evidence/reactome-paths.yaml |
| GO:0002160 desmosome maintenance | IEA GO_REF:0000107 | ACCEPT | Summary: The literal donor is mouse Dsp/E9Q557. Reason: The literal donor is mouse Dsp/E9Q557. Mouse loss-of-function and rescue evidence supports the persistence and functional integrity of desmosomal attachments, and human DSP mutations and junctional-cell experiments independently support the conserved structural role. The target itself supplies the plaque–intermediate-filament link; it is not merely a downstream disease marker. Preserve the original orthology/source assertion rather than treating it as a new human experiment. Propagation Review Root cause: NO FAILURE CORE |
| GO:0002160 desmosome maintenance | ISS GO_REF:0000024 | ACCEPT | Summary: The literal donor is mouse Dsp/E9Q557. Reason: The literal donor is mouse Dsp/E9Q557. Mouse loss-of-function and rescue evidence supports the persistence and functional integrity of desmosomal attachments, and human DSP mutations and junctional-cell experiments independently support the conserved structural role. The target itself supplies the plaque–intermediate-filament link; it is not merely a downstream disease marker. Preserve the original orthology/source assertion rather than treating it as a new human experiment. Propagation Review Root cause: NO FAILURE CORE |
| GO:0002934 desmosome organization | IEA GO_REF:0000107 | ACCEPT | Summary: The traced mouse Dsp donor has direct desmosome-organization annotations. Reason: The traced mouse Dsp donor has direct desmosome-organization annotations. Mouse Dsp deletion disrupts desmosomal structure and intermediate-filament anchorage, while human DSP head-domain plaque clustering and human cellular junction-assembly assays independently establish the corresponding target contribution. The source transfer is biologically coherent; the organism and construct evidence remain separate. Propagation Review Root cause: NO FAILURE CORE |
| GO:0002934 desmosome organization | ISS GO_REF:0000024 | ACCEPT | Summary: The traced mouse Dsp donor has direct desmosome-organization annotations. Reason: The traced mouse Dsp donor has direct desmosome-organization annotations. Mouse Dsp deletion disrupts desmosomal structure and intermediate-filament anchorage, while human DSP head-domain plaque clustering and human cellular junction-assembly assays independently establish the corresponding target contribution. The source transfer is biologically coherent; the organism and construct evidence remain separate. Propagation Review Root cause: NO FAILURE CORE |
| GO:0002934 desmosome organization | ISS PMID:16917092 Desmosomal dysfunction due to mutations in desmoplakin cause... | ACCEPT | Summary: PMID:16917092 reports human cardiomyopathy-associated DSP mutants and transgenic mouse cardiac phenotypes affecting junctional organization. Reason: PMID:16917092 reports human cardiomyopathy-associated DSP mutants and transgenic mouse cardiac phenotypes affecting junctional organization. Its abstract and the exact mouse donor annotation support the inherited process; the full target-specific body was not recovered. Independent human plaque-assembly and trafficking experiments establish the same gene-level organization function, so the curator-supported assertion is retained without inventing an unread mutant assay. Propagation Review Root cause: NO FAILURE CORE |
| GO:0003223 ventricular compact myocardium morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The exact donor is mouse Dsp/E9Q557 and the cited cardiac study reports cardiac-targeted mutant DSP transgenes, deficient intercalated discs and dysplastic ventricular myocardium. Reason: The exact donor is mouse Dsp/E9Q557 and the cited cardiac study reports cardiac-targeted mutant DSP transgenes, deficient intercalated discs and dysplastic ventricular myocardium. Retain the conserved developmental context, distinct from the immediate plaque-linking activity. The available abstract is positive, but does not authenticate every construct or make this a direct human morphogenesis experiment. Propagation Review Root cause: NO FAILURE NON CORE |
| GO:0003223 ventricular compact myocardium morphogenesis | ISS PMID:16917092 Desmosomal dysfunction due to mutations in desmoplakin cause... | KEEP AS NON CORE | Summary: The exact donor is mouse Dsp/E9Q557 and the cited cardiac study reports cardiac-targeted mutant DSP transgenes, deficient intercalated discs and dysplastic ventricular myocardium. Reason: The exact donor is mouse Dsp/E9Q557 and the cited cardiac study reports cardiac-targeted mutant DSP transgenes, deficient intercalated discs and dysplastic ventricular myocardium. Retain the conserved developmental context, distinct from the immediate plaque-linking activity. The available abstract is positive, but does not authenticate every construct or make this a direct human morphogenesis experiment. Propagation Review Root cause: NO FAILURE NON CORE Supporting Evidence: |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | KEEP AS NON CORE | Summary: Genuine PMID:22658674 Table S1 lists DSP/ENSG00000096696 at Excel row 139 as an mRNA-interactome protein: identified in crosslinked samples, not identified in control, adjusted ion-count p=0.00264221421315189 and spectral-count p=0.0166297092443137. Reason: Genuine PMID:22658674 Table S1 lists DSP/ENSG00000096696 at Excel row 139 as an mRNA-interactome protein: identified in crosslinked samples, not identified in control, adjusted ion-count p=0.00264221421315189 and spectral-count p=0.0166297092443137. The HeLa UV-crosslink/oligo(dT) procedure used stringent detergent/salt washing and RNase release; the paper accepts enrichment by either statistical method. This is positive RNA-contact evidence in that assay, without a defined DSP RNA target, RNA-regulatory mechanism or independently validated natural-product specificity. Retain it outside the structural core. |
| GO:0005080 protein kinase C binding | IPI PMID:18474624 Plakophilin 2: a critical scaffold for PKC alpha that regula... | KEEP AS NON CORE | Summary: The original reports DSP association with tagged PKC-alpha in HEK293 cells and dependence of that association on PKP2. Reason: The original reports DSP association with tagged PKC-alpha in HEK293 cells and dependence of that association on PKP2. This supports a kinase-associated junctional complex, not a purified binary interface or DSP kinase activity. The imported partner P04409 is the bovine PRKCA accession; the host cell and separately described human retroviral construct do not authenticate the species of every FLAG reagent. Preserve the exact source partner and contextual class assertion rather than silently rewriting it. Supporting Evidence: |
| GO:0005198 structural molecule activity | IBA GO_REF:0000033 | MODIFY | Summary: The genuine PAINT IBD is on PTN002753757, and the human DSP leaf descends from it without an intervening target-path loss annotation. Reason: The genuine PAINT IBD is on PTN002753757, and the human DSP leaf descends from it without an intervening target-path loss annotation. The broad structural inference is valid. Human plaque-linkage evidence and conserved intermediate-filament anchorage permit the more informative structural constituent of cytoskeleton term; this is a target-level refinement, not a claim that every donor experiment directly tested human DSP. The fixed PAINT audit preserves the literal IBD, target lineage, descendant donor identities and absence of an intervening target-path IRD; donor count is not used to overrule the curator. Propagation Review Root cause: TERM SCOPING PROBLEM Proposed replacements: structural constituent of cytoskeleton |
| GO:0005198 structural molecule activity | IEA GO_REF:0000117 | MODIFY | Summary: The ARBA source asserts structural molecule activity, which is biologically correct but broad for DSP. Reason: The ARBA source asserts structural molecule activity, which is biologically correct but broad for DSP. Its experimentally supported plaque–intermediate-filament linkage contributes to cytoskeletal integrity, satisfying the current definition of structural constituent of cytoskeleton. The refinement is anchored to target and conserved primary evidence rather than treating the automatic rule as a biochemical experiment. Propagation Review Root cause: TERM SCOPING PROBLEM Proposed replacements: structural constituent of cytoskeleton |
| GO:0005200 structural constituent of cytoskeleton | TAS PMID:9887343 Haploinsufficiency of desmoplakin causes a striate subtype o... | ACCEPT | Summary: The human truncating-variant study reports skin fragility and disrupted attachment of intermediate filaments to desmosomes. Reason: The human truncating-variant study reports skin fragility and disrupted attachment of intermediate filaments to desmosomes. Together with direct human plaque-domain and IF-interaction evidence, this supports DSP as a structural cytoskeletal constituent. The disease association corroborates a physical linkage established independently; it does not imply that each natural splice product was tested. |
| GO:0005515 protein binding | IPI PMID:10852826 Interaction of plakophilins with desmoplakin and intermediat... | MODIFY | Summary: The imported source identifies Q13835-2 and the original abstract reports PKP1a–DSP co-immunoprecipitation in HaCaT cells. Reason: The imported source identifies Q13835-2 and the original abstract reports PKP1a–DSP co-immunoprecipitation in HaCaT cells. PKP1 is a desmosomal scaffold that organizes multiple plaque partners. Independent original PMID:11790773 Figure 6 reports binary yeast two-hybrid binding between DSP-NTP and the PKP1 head, alongside cellular co-immunoprecipitation; full-length and fragment experiments are distinguished. The class refinement describes recognition of that partner, not transfer of PKP1 signaling, translation or enzymatic activities to DSP. The original isoform identifier remains unchanged; no exact modern sequence equivalence is inferred solely from the name PKP1a. Proposed replacements: scaffold protein binding |
| GO:0005515 protein binding | IPI PMID:11790773 Protein binding and functional characterization of plakophil... | MODIFY | Summary: PKP1 is a desmosomal scaffold that organizes multiple plaque partners. Reason: PKP1 is a desmosomal scaffold that organizes multiple plaque partners. Independent original PMID:11790773 Figure 6 reports binary yeast two-hybrid binding between DSP-NTP and the PKP1 head, alongside cellular co-immunoprecipitation; full-length and fragment experiments are distinguished. The class refinement describes recognition of that partner, not transfer of PKP1 signaling, translation or enzymatic activities to DSP. The recovered original Methods/Results specify the DSP N-terminal construct and PKP1a comparison; they do not establish an interaction unique to one current DSP product. Proposed replacements: scaffold protein binding |
| GO:0005515 protein binding | IPI PMID:11790773 Protein binding and functional characterization of plakophil... | MODIFY | Summary: The recovered original demonstrates DSP-NTP–PKP2 interaction in binary yeast two-hybrid assays and co-immunoprecipitation of full-length DSP or DSP-NTP with PKP2a. Reason: The recovered original demonstrates DSP-NTP–PKP2 interaction in binary yeast two-hybrid assays and co-immunoprecipitation of full-length DSP or DSP-NTP with PKP2a. PKP2 is a desmosomal cytoskeletal plaque component, so cytoskeletal protein binding is a supported partner-class refinement. It does not imply that DSP itself performs PKP2-dependent signaling or directly binds intermediate filaments through the same head-domain interface. The class provenance is explicit: human PKP2/Q99959 GO:0005882 annotation !328040827 is ISS via mouse Q9CQ73; rat F1M7L9 !57565728 is ISO via MGI:1914701, which the official mouse record joins to Q9CQ73. Mouse annotation !357919950 is IDA from PMID:16917092. GO:0005882 lies within the cytoskeleton branch. The mouse donor body remains unavailable; these are curator-supported component annotations, not independently read human or rat microscopy or proof that PKP2 polymerizes filaments. Proposed replacements: cytoskeletal protein binding |
| GO:0005515 protein binding | IPI PMID:12482924 Analysis of the interactions between BP180, BP230, plectin a... | UNDECIDED | Summary: The imported interaction is specifically with COL17A1/Q9UMD9. Reason: The imported interaction is specifically with COL17A1/Q9UMD9. The identifier and official target subunit annotation are consistent, but the recovered abstract of PMID:12482924 foregrounds BP180/BP230/plectin and does not expose the DSP-specific construct, controls or result. Bounded publisher and full-text recovery failed. This is not evidence of wrong-gene curation or a negative DSP interaction; defer a narrower class judgment until the target-specific full assay can be inspected. |
| GO:0005515 protein binding | IPI PMID:16917092 Desmosomal dysfunction due to mutations in desmoplakin cause... | MODIFY | Summary: The supplied source describes cardiomyopathy-associated DSP mutants with altered JUP association; full source-specific Methods remain unavailable. Reason: The supplied source describes cardiomyopathy-associated DSP mutants with altered JUP association; full source-specific Methods remain unavailable. Independently, the recovered human DSP N-terminal plaque study establishes JUP binding and clustering. JUP/P14923 is gamma-catenin, making gamma-catenin binding a supported gene-level refinement while preserving the original source and its mutant/organism limitations. Proposed replacements: gamma-catenin binding |
| GO:0005515 protein binding | IPI PMID:19136012 The desmoglein-specific cytoplasmic region is intrinsically ... | MODIFY | Summary: The original abstract explicitly reports weak but direct binding of the human DSG1-specific cytoplasmic region to the DSP plakin domain. Reason: The original abstract explicitly reports weak but direct binding of the human DSG1-specific cytoplasmic region to the DSP plakin domain. DSG1/Q02413 is a desmosomal cadherin. Cadherin binding therefore specifies the positive pair without claiming DSP is a cadherin or that the isolated-tail assay proves every native full-length interface. Full Methods were not recovered. Proposed replacements: cadherin binding |
| GO:0005515 protein binding | IPI PMID:21062920 Mechanistic insights into arrhythmogenic right ventricular c... | MODIFY | Summary: The independently read primary source tests human DSC2 cytoplasmic tails and a DSP N-terminal fragment, with the DSC2a/b distinction retained in the source advice. Reason: The independently read primary source tests human DSC2 cytoplasmic tails and a DSP N-terminal fragment, with the DSC2a/b distinction retained in the source advice. DSC2/Q02487 is a desmosomal cadherin; cadherin binding is the appropriate partner class. The fragment result does not establish equivalent interfaces for all DSC2 tails or current DSP splice products. Proposed replacements: cadherin binding |
| GO:0005515 protein binding | IPI PMID:21756917 The nonlinear structure of the desmoplakin plakin domain and... | MODIFY | Summary: The curator-supported partner is PKP1/Q13835. Reason: The curator-supported partner is PKP1/Q13835. The original PMID and abstract were authenticated, but this paper's full target-specific interaction experiment was not recovered. PKP1 is a desmosomal scaffold that organizes multiple plaque partners. Independent original PMID:11790773 Figure 6 reports binary yeast two-hybrid binding between DSP-NTP and the PKP1 head, alongside cellular co-immunoprecipitation; full-length and fragment experiments are distinguished. The class refinement describes recognition of that partner, not transfer of PKP1 signaling, translation or enzymatic activities to DSP. The independent binary result supports the gene-level refinement without fabricating details of the inaccessible structural or phosphorylation experiment. Proposed replacements: scaffold protein binding |
| GO:0005515 protein binding | IPI PMID:23444369 Insulin signaling via Akt2 switches plakophilin 1 function f... | MODIFY | Summary: The curator-supported partner is PKP1/Q13835. Reason: The curator-supported partner is PKP1/Q13835. The original PMID and abstract were authenticated, but this paper's full target-specific interaction experiment was not recovered. PKP1 is a desmosomal scaffold that organizes multiple plaque partners. Independent original PMID:11790773 Figure 6 reports binary yeast two-hybrid binding between DSP-NTP and the PKP1 head, alongside cellular co-immunoprecipitation; full-length and fragment experiments are distinguished. The class refinement describes recognition of that partner, not transfer of PKP1 signaling, translation or enzymatic activities to DSP. The independent binary result supports the gene-level refinement without fabricating details of the inaccessible structural or phosphorylation experiment. Proposed replacements: scaffold protein binding |
| GO:0005515 protein binding | IPI PMID:25225338 Disease mutations in desmoplakin inhibit Cx43 membrane targe... | MODIFY | Summary: The human HeLa-library yeast two-hybrid screen and targeted assays identify EB1/MAPRE1 binding to DSP-NTP; endogenous human keratinocyte co-IP/PLA/SIM and EB1-binding-deficient DSP mutants provide independent cellular context. Reason: The human HeLa-library yeast two-hybrid screen and targeted assays identify EB1/MAPRE1 binding to DSP-NTP; endogenous human keratinocyte co-IP/PLA/SIM and EB1-binding-deficient DSP mutants provide independent cellular context. MAPRE1/Q15691 is a microtubule-associated cytoskeletal protein, making cytoskeletal protein binding a supported class. Lysate pull-downs are not two-purified-protein assays, and binding EB1 is not itself direct DSP–microtubule binding. Proposed replacements: cytoskeletal protein binding |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: The exact human DSP–FES pair EBI-10103287 is an anti-tag co-immunoprecipitation with FLAG-tagged FES bait in the curated DLD-1 context. Reason: The exact human DSP–FES pair EBI-10103287 is an anti-tag co-immunoprecipitation with FLAG-tagged FES bait in the curated DLD-1 context. Independent human FES AP-MS corroborates the association. FES/P07332 is an experimentally supported protein tyrosine kinase, and the current GO:0019901 definition requires binding to a protein kinase without specifying catalytic-site recognition or purified reconstitution. Protein kinase binding is therefore an informative partner-class refinement under the project binding policy. The association assays do not establish a purified direct interface, and no FES catalytic activity is transferred to DSP. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:28891468 Epidermal Growth Factor Receptor neddylation is regulated by... | KEEP AS NON CORE | Summary: Retain the experimentally supported DSP–COPS3 association as non-core binding. Reason: Endogenous DSP–COPS3 co-immunoprecipitation in human keratinocytes, DSP C-terminal capture from SCC9 lysate and controlled proximity assays support the association. The negative yeast assay concerns only DSP residues 1–584 and does not contradict those results. COPS3 is a COP9 subunit; its complex's deneddylase chemistry and recruitment to desmosomes do not establish the catalytic-partner or signaling-scaffold class required by the considered refinements. Retain the positive interaction as contextual non-core binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31595153 Nuclear localization of Desmoplakin and its involvement in t... | KEEP AS NON CORE | Summary: Retain the experimentally supported DSP–TERF2 association as non-core binding. Reason: Human HEK293/MCF-7 co-immunoprecipitation, NLS dependence and TRF2-dependent telomeric DSP signals support association with TERF2/Q15554. TERF2's telomeric DNA-binding and factor-recruitment roles do not identify it as a DNA-binding transcription factor, and these observations do not establish another more informative DSP molecular function. Retain the positive association and nuclear/telomere context as non-core binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: The exact record EBI-28931656 identifies DSP as prey of human N-terminal Strep/HA-tagged FES in HEK293 Flp-In T-REx AP-MS. Reason: The exact record EBI-28931656 identifies DSP as prey of human N-terminal Strep/HA-tagged FES in HEK293 Flp-In T-REx AP-MS. The association is spoke-expanded from the experiment and is independently corroborated by the FES co-immunoprecipitation source. The verified FES/P07332 protein-kinase class supports GO:0019901 protein kinase binding; its definition does not require an isolated catalytic-site-recognition experiment. This refinement retains the assay and construct limits, does not claim purified direct contact and does not assign kinase activity to DSP. Proposed replacements: protein kinase binding |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | KEEP AS NON CORE | Summary: The authentic author thesis linked to PMID:21630459 contains its study-specific Annex 8.2/Table 8.1: DSP/P15924 has 2.1% sequence coverage and three peptides in isolated normozoospermic sperm nuclei. Reason: The authentic author thesis linked to PMID:21630459 contains its study-specific Annex 8.2/Table 8.1: DSP/P15924 has 2.1% sequence coverage and three peptides in isolated normozoospermic sperm nuclei. The CTAB/DTT decapitation, repeated digitonin washes and microscopy quality-control procedure was read. This is positive fraction detection, not an assumed contaminant. It does not resolve a native intranuclear mechanism or distinguish current DSP isoforms; the later chromatin-fraction tables in the same thesis are not substituted for this study. Supporting Evidence: https://diposit.ub.edu/dspace/handle/2445/60858 file:human/DSP/DSP-evidence/measurements.yaml |
| GO:0005634 nucleus | IDA PMID:31595153 Nuclear localization of Desmoplakin and its involvement in t... | KEEP AS NON CORE | Summary: The recovered original directly reports nuclear fractionation/imaging and telomere-associated DSP in human cultured cells, including perturbation and rescue. Reason: The recovered original directly reports nuclear fractionation/imaging and telomere-associated DSP in human cultured cells, including perturbation and rescue. These positive results support a nonexclusive nuclear pool; telomeric ChIP/co-localization and TRF2 dependence do not establish purified DNA binding or turn the nuclear observations into the principal structural function. Supporting Evidence: |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The current UniProt subcellular-location mapping is corroborated by independently read human nuclear fractionation/imaging and by the separate sperm-nucleus proteomic detection. Reason: The current UniProt subcellular-location mapping is corroborated by independently read human nuclear fractionation/imaging and by the separate sperm-nucleus proteomic detection. Retain a nonexclusive contextual nuclear pool, preserving the original electronic evidence and not treating its mapped location as a new experiment. Propagation Review Root cause: NO FAILURE NON CORE |
| GO:0005737 cytoplasm | EXP PMID:25208567 Plakophilin 3 mediates Rap1-dependent desmosome assembly and... | ACCEPT | Summary: The original human epithelial-cell experiments directly show cytoplasmic DSP precursor particles and their recruitment to cell contacts; PKP3 loss also alters the soluble and cytoskeletal distributions. Reason: The original human epithelial-cell experiments directly show cytoplasmic DSP precursor particles and their recruitment to cell contacts; PKP3 loss also alters the soluble and cytoskeletal distributions. This is a functional cytoplasmic assembly pool. The broad cytoplasm term is retained because particles and filament-associated material should not all be equated with free soluble cytosol. Supporting Evidence: |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: The literal PAINT IBD on PTN002753757 lies above the human DSP leaf, with no target-path loss annotation. Reason: The literal PAINT IBD on PTN002753757 lies above the human DSP leaf, with no target-path loss annotation. DSP itself appears among descendant experimental sources, which is valid phylogenetic grounding rather than circularity. Human cytoplasmic assembly-particle and junction-trafficking experiments independently support the inherited activity/localization context. Do not replace all of this pool with soluble cytosol. The fixed PAINT audit preserves the literal IBD, target lineage, descendant donor identities and absence of an intervening target-path IRD; donor count is not used to overrule the curator. Propagation Review Root cause: NO FAILURE CORE |
| GO:0005737 cytoplasm | IDA PMID:17475244 Increased keratinocyte proliferation initiated through downr... | ACCEPT | Summary: The original source is authenticated and its HaCaT DSP-depletion context is explicit in the abstract, although full source-specific imaging Methods were not recovered. Reason: The original source is authenticated and its HaCaT DSP-depletion context is explicit in the abstract, although full source-specific imaging Methods were not recovered. Independently read human epithelial experiments directly establish cytoplasmic DSP assembly particles and trafficking. Retain the curator-supported broad pool without asserting that the inaccessible experiment measured a particular soluble fraction. |
| GO:0005737 cytoplasm | IDA PMID:25225338 Disease mutations in desmoplakin inhibit Cx43 membrane targe... | ACCEPT | Summary: The recovered original directly studies endogenous or engineered DSP in human epithelial cells, including cytoplasmic material and junction-associated trafficking/complexes. Reason: The recovered original directly studies endogenous or engineered DSP in human epithelial cells, including cytoplasmic material and junction-associated trafficking/complexes. The cytoplasmic pool is biologically integral to assembly and recruitment. It is not exclusively a soluble cytosol pool, and the source does not justify discarding nonjunctional DSP. Supporting Evidence: |
| GO:0005737 cytoplasm | IDA PMID:28891468 Epidermal Growth Factor Receptor neddylation is regulated by... | ACCEPT | Summary: The recovered original directly studies endogenous or engineered DSP in human epithelial cells, including cytoplasmic material and junction-associated trafficking/complexes. Reason: The recovered original directly studies endogenous or engineered DSP in human epithelial cells, including cytoplasmic material and junction-associated trafficking/complexes. The cytoplasmic pool is biologically integral to assembly and recruitment. It is not exclusively a soluble cytosol pool, and the source does not justify discarding nonjunctional DSP. Supporting Evidence: |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: The literal mouse Dsp donor and official cytoplasm mapping agree with the conserved cytoplasmic DSP pool. Reason: The literal mouse Dsp donor and official cytoplasm mapping agree with the conserved cytoplasmic DSP pool. Independent human studies visualize precursor particles, cytoplasmic redistribution and junctional recruitment. Retain the broad term with the original inferred source rather than recasting these data as a human soluble-fraction assay. Propagation Review Root cause: NO FAILURE CORE |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: The literal mouse Dsp donor and official cytoplasm mapping agree with the conserved cytoplasmic DSP pool. Reason: The literal mouse Dsp donor and official cytoplasm mapping agree with the conserved cytoplasmic DSP pool. Independent human studies visualize precursor particles, cytoplasmic redistribution and junctional recruitment. Retain the broad term with the original inferred source rather than recasting these data as a human soluble-fraction assay. Propagation Review Root cause: NO FAILURE CORE |
| GO:0005856 cytoskeleton | IEA GO_REF:0000002 | MODIFY | Summary: The InterPro-derived cytoskeleton assertion is broadly correct. Reason: The InterPro-derived cytoskeleton assertion is broadly correct. DSP's experimentally established intermediate-filament linkage and its conserved localization with the IF network support intermediate filament cytoskeleton as a more informative anatomical structure. This does not claim that DSP is an intermediate-filament polymer subunit or alter the separate colocalizes_with qualifiers of the imported IF annotations. Propagation Review Root cause: TERM SCOPING PROBLEM Proposed replacements: intermediate filament cytoskeleton |
| GO:0005882 intermediate filament | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT assertion on PTN002753757 propagates to DSP through the verified target path. Reason: The PAINT assertion on PTN002753757 propagates to DSP through the verified target path. Its original colocalizes_with qualifier is retained: the target links and associates with intermediate filaments rather than being asserted to polymerize as an IF subunit. Human binding/localization and mouse network-disruption data independently support this conserved relationship. The fixed PAINT audit preserves the literal IBD, target lineage, descendant donor identities and absence of an intervening target-path IRD; donor count is not used to overrule the curator. Propagation Review Root cause: NO FAILURE CORE |
| GO:0005882 intermediate filament | IEA GO_REF:0000107 | ACCEPT | Summary: The exact mouse Dsp donor supports IF association in the cardiac/desmosomal context, and human DSP tail–IF evidence independently corroborates it. Reason: The exact mouse Dsp donor supports IF association in the cardiac/desmosomal context, and human DSP tail–IF evidence independently corroborates it. Preserve colocalizes_with, the original donor and the source paper; do not silently convert the relationship to part_of or infer identical function of every natural splice product. Propagation Review Root cause: NO FAILURE CORE |
| GO:0005882 intermediate filament | ISS PMID:16917092 Desmosomal dysfunction due to mutations in desmoplakin cause... | ACCEPT | Summary: The exact mouse Dsp donor supports IF association in the cardiac/desmosomal context, and human DSP tail–IF evidence independently corroborates it. Reason: The exact mouse Dsp donor supports IF association in the cardiac/desmosomal context, and human DSP tail–IF evidence independently corroborates it. Preserve colocalizes_with, the original donor and the source paper; do not silently convert the relationship to part_of or infer identical function of every natural splice product. Propagation Review Root cause: NO FAILURE CORE |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: The verified PAINT IBD at PTN002753793 includes the human DSP descendant; target self-evidence is legitimate grounding. Reason: The verified PAINT IBD at PTN002753793 includes the human DSP descendant; target self-evidence is legitimate grounding. DSP functions at the cytoplasmic surface of membrane-associated junctional plaques, which satisfies this nonexclusive plasma-membrane context without making DSP an integral membrane protein. The membrane-associated pool spans several junction types. The fixed PAINT audit preserves the literal IBD, target lineage, descendant donor identities and absence of an intervening target-path IRD; donor count is not used to overrule the curator. Propagation Review Root cause: NO FAILURE CORE |
| GO:0005886 plasma membrane | IDA PMID:11790773 Protein binding and functional characterization of plakophil... | ACCEPT | Summary: The recovered original directly shows DSP recruitment and co-localization at epithelial cell borders with desmosomal plaque partners. Reason: The recovered original directly shows DSP recruitment and co-localization at epithelial cell borders with desmosomal plaque partners. Plasma-membrane association is retained as a peripheral junctional pool, not a transmembrane topology claim; the same source distinguishes full DSP and N-terminal fragment experiments. Supporting Evidence: |
| GO:0005886 plasma membrane | IDA PMID:16917092 Desmosomal dysfunction due to mutations in desmoplakin cause... | ACCEPT | Summary: The authenticated original is curator-supported for membrane localization; its full target-specific localization Methods were not recovered. Reason: The authenticated original is curator-supported for membrane localization; its full target-specific localization Methods were not recovered. Independent human cell-border imaging and desmosomal plaque experiments establish the same gene-level pool. Retain this established anatomical pool without pretending the inaccessible paper was read in full or that all membrane-associated DSP is in one uniform compartment. |
| GO:0005886 plasma membrane | IDA PMID:17475244 Increased keratinocyte proliferation initiated through downr... | ACCEPT | Summary: The authenticated original is curator-supported for membrane localization; its full target-specific localization Methods were not recovered. Reason: The authenticated original is curator-supported for membrane localization; its full target-specific localization Methods were not recovered. Independent human cell-border imaging and desmosomal plaque experiments establish the same gene-level pool. Retain this established anatomical pool without pretending the inaccessible paper was read in full or that all membrane-associated DSP is in one uniform compartment. |
| GO:0005886 plasma membrane | IDA PMID:25225338 Disease mutations in desmoplakin inhibit Cx43 membrane targe... | ACCEPT | Summary: Human keratinocyte imaging and the junctional EB1/Cx43 experiments directly establish membrane-associated DSP at cell contacts. Reason: Human keratinocyte imaging and the junctional EB1/Cx43 experiments directly establish membrane-associated DSP at cell contacts. This is a peripheral plaque/trafficking role, not insertion through a lipid bilayer. The original also supports a cytoplasmic pool, so the locations are nonexclusive. Supporting Evidence: |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: The traced mouse Dsp source and official subcellular mapping support the same membrane-associated plaque pool independently demonstrated in human epithelial cells. Reason: The traced mouse Dsp source and official subcellular mapping support the same membrane-associated plaque pool independently demonstrated in human epithelial cells. Preserve the inferred source identity and nonexclusive plasma-membrane pool; neither integral-membrane topology nor exclusivity to desmosomes is asserted. Propagation Review Root cause: NO FAILURE CORE |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: The traced mouse Dsp source and official subcellular mapping support the same membrane-associated plaque pool independently demonstrated in human epithelial cells. Reason: The traced mouse Dsp source and official subcellular mapping support the same membrane-associated plaque pool independently demonstrated in human epithelial cells. Preserve the inferred source identity and nonexclusive plasma-membrane pool; neither integral-membrane topology nor exclusivity to desmosomes is asserted. Propagation Review Root cause: NO FAILURE CORE |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201636 | ACCEPT | Summary: The saved current Reactome event 201636 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). Reason: The saved current Reactome event 201636 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). This agrees with independent human junctional imaging. Retain the anatomical pool; complex membership and reaction context do not assign the event's catalytic activity to DSP. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6800426 | ACCEPT | Summary: The saved current Reactome event 6800426 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). Reason: The saved current Reactome event 6800426 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). This agrees with independent human junctional imaging. Retain the anatomical pool; complex membership and reaction context do not assign the event's catalytic activity to DSP. In this event DSP is a literal hasMember of the ficolin-rich membrane set. The curated model is positive but does not itself verify the underlying DSP-specific neutrophil fraction measurement; that narrower granule assertion is assessed separately. Supporting Evidence: Reactome:R-HSA-6800426 file:human/DSP/DSP-evidence/reactome-paths.yaml |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6809393 | ACCEPT | Summary: The saved current Reactome event 6809393 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). Reason: The saved current Reactome event 6809393 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). This agrees with independent human junctional imaging. Retain the anatomical pool; complex membership and reaction context do not assign the event's catalytic activity to DSP. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6810357 | ACCEPT | Summary: The saved current Reactome event 6810357 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). Reason: The saved current Reactome event 6810357 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). This agrees with independent human junctional imaging. Retain the anatomical pool; complex membership and reaction context do not assign the event's catalytic activity to DSP. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6810937 | ACCEPT | Summary: The saved current Reactome event 6810937 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). Reason: The saved current Reactome event 6810937 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). This agrees with independent human junctional imaging. Retain the anatomical pool; complex membership and reaction context do not assign the event's catalytic activity to DSP. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6811539 | ACCEPT | Summary: The saved current Reactome event 6811539 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). Reason: The saved current Reactome event 6811539 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). This agrees with independent human junctional imaging. Retain the anatomical pool; complex membership and reaction context do not assign the event's catalytic activity to DSP. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6814298 | ACCEPT | Summary: The saved current Reactome event 6814298 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). Reason: The saved current Reactome event 6814298 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). This agrees with independent human junctional imaging. Retain the anatomical pool; complex membership and reaction context do not assign the event's catalytic activity to DSP. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6814387 | ACCEPT | Summary: The saved current Reactome event 6814387 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). Reason: The saved current Reactome event 6814387 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). This agrees with independent human junctional imaging. Retain the anatomical pool; complex membership and reaction context do not assign the event's catalytic activity to DSP. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6814695 | ACCEPT | Summary: The saved current Reactome event 6814695 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). Reason: The saved current Reactome event 6814695 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). This agrees with independent human junctional imaging. Retain the anatomical pool; complex membership and reaction context do not assign the event's catalytic activity to DSP. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6814734 | ACCEPT | Summary: The saved current Reactome event 6814734 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). Reason: The saved current Reactome event 6814734 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). This agrees with independent human junctional imaging. Retain the anatomical pool; complex membership and reaction context do not assign the event's catalytic activity to DSP. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6814764 | ACCEPT | Summary: The saved current Reactome event 6814764 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). Reason: The saved current Reactome event 6814764 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). This agrees with independent human junctional imaging. Retain the anatomical pool; complex membership and reaction context do not assign the event's catalytic activity to DSP. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8942224 | ACCEPT | Summary: The saved current Reactome event 8942224 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). Reason: The saved current Reactome event 8942224 has an exact input/output membership path to human DSP/P15924 at plasma membrane (entity 201580, nominal residues 1–2871; the cleavage product in 201636 has unresolved boundaries). This agrees with independent human junctional imaging. Retain the anatomical pool; complex membership and reaction context do not assign the event's catalytic activity to DSP. |
| GO:0005911 cell-cell junction | IEA GO_REF:0000107 | MODIFY | Summary: The mouse orthology assertion correctly identifies a cell-cell junction. Reason: The mouse orthology assertion correctly identifies a cell-cell junction. Human plaque assembly/localization and conserved IF linkage support the more informative desmosome location for the established principal junctional pool. This is a gene-level refinement and does not deny the separately retained cardiac area-composita/adherens or nonjunctional locations. Propagation Review Root cause: TERM SCOPING PROBLEM Proposed replacements: desmosome |
| GO:0005912 adherens junction | IEA GO_REF:0000107 | ACCEPT | Summary: The literal mouse donor is supported by the recovered PMID:15479741 immunoelectron microscopy: DSP labels both desmosome-like and fascia-adhaerens-type plaques in embryonic cardiac intercalated discs, including fused areae compositae. Reason: The literal mouse donor is supported by the recovered PMID:15479741 immunoelectron microscopy: DSP labels both desmosome-like and fascia-adhaerens-type plaques in embryonic cardiac intercalated discs, including fused areae compositae. The source is positive localization rather than an assumption from a desmosomal name. Retain this junctional context without claiming universal residence in epithelial adherens junctions. Propagation Review Root cause: NO FAILURE CORE |
| GO:0005912 adherens junction | ISS GO_REF:0000024 | ACCEPT | Summary: The literal mouse donor is supported by the recovered PMID:15479741 immunoelectron microscopy: DSP labels both desmosome-like and fascia-adhaerens-type plaques in embryonic cardiac intercalated discs, including fused areae compositae. Reason: The literal mouse donor is supported by the recovered PMID:15479741 immunoelectron microscopy: DSP labels both desmosome-like and fascia-adhaerens-type plaques in embryonic cardiac intercalated discs, including fused areae compositae. The source is positive localization rather than an assumption from a desmosomal name. Retain this junctional context without claiming universal residence in epithelial adherens junctions. Propagation Review Root cause: NO FAILURE CORE |
| GO:0005916 fascia adherens | IEA GO_REF:0000107 | ACCEPT | Summary: The rat Dsp donor and PMID:16406610 support DSP at fascia-adhaerens-like cardiac junctions. Reason: The rat Dsp donor and PMID:16406610 support DSP at fascia-adhaerens-like cardiac junctions. The authenticated primary abstract explicitly includes human, bovine, rat and mouse immunoelectron microscopy and recognizes mixed areae compositae; independently recovered mouse original images' captions and Results agree. Retain the anatomical assertion without making every adherens junction a desmosome. Propagation Review Root cause: NO FAILURE CORE |
| GO:0007281 germ cell development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The exact mouse donor experiment deletes Dsp in NR5A1-positive gonadal somatic cells and finds reduced germ-cell survival in fetal testes and ovaries. Reason: The exact mouse donor experiment deletes Dsp in NR5A1-positive gonadal somatic cells and finds reduced germ-cell survival in fetal testes and ovaries. The original abstract explicitly distinguishes this from altered sex determination. This is positive non-cell-autonomous developmental context through somatic-cell adhesion, not evidence for a new DSP catalytic function or a germ-cell-intrinsic human assay. Propagation Review Root cause: NO FAILURE NON CORE |
| GO:0007281 germ cell development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The exact mouse donor experiment deletes Dsp in NR5A1-positive gonadal somatic cells and finds reduced germ-cell survival in fetal testes and ovaries. Reason: The exact mouse donor experiment deletes Dsp in NR5A1-positive gonadal somatic cells and finds reduced germ-cell survival in fetal testes and ovaries. The original abstract explicitly distinguishes this from altered sex determination. This is positive non-cell-autonomous developmental context through somatic-cell adhesion, not evidence for a new DSP catalytic function or a germ-cell-intrinsic human assay. Propagation Review Root cause: NO FAILURE NON CORE |
| GO:0008544 epidermis development | TAS PMID:9887343 Haploinsufficiency of desmoplakin causes a striate subtype o... | KEEP AS NON CORE | Summary: The human loss-of-function study provides positive epidermal disease and tissue-architecture evidence, consistent with the conserved requirement for DSP-linked desmosomes in skin integrity. Reason: The human loss-of-function study provides positive epidermal disease and tissue-architecture evidence, consistent with the conserved requirement for DSP-linked desmosomes in skin integrity. Retain the developmental context alongside the immediate junctional structural role; the genetic association does not by itself specify a separate developmental biochemical activity. |
| GO:0014704 intercalated disc | IBA GO_REF:0000033 | ACCEPT | Summary: The literal PAINT assertion at PTN002753793 is inherited by DSP; human self-evidence is valid descendant grounding. Reason: The literal PAINT assertion at PTN002753793 is inherited by DSP; human self-evidence is valid descendant grounding. Cardiac intercalated discs contain DSP-positive desmosomal and mixed adhering junctions, supported by human source annotations and the independently inspected ortholog original. Retain this tissue-specific functional location within the junctional mechanism. The fixed PAINT audit preserves the literal IBD, target lineage, descendant donor identities and absence of an intervening target-path IRD; donor count is not used to overrule the curator. Propagation Review Root cause: NO FAILURE CORE |
| GO:0014704 intercalated disc | IDA PMID:22781308 Molecular insights into arrhythmogenic right ventricular car... | ACCEPT | Summary: The authenticated source reports human PKP2-associated cardiac disease, reduced intercalated-disc proteins in patient myocardium and a separate HL-1 interaction model. Reason: The authenticated source reports human PKP2-associated cardiac disease, reduced intercalated-disc proteins in patient myocardium and a separate HL-1 interaction model. Preserve the curated DSP localization. The human tissue observation and murine cell model are not collapsed into an all-human DSP perturbation assay; independent cardiac localization evidence corroborates the compartment. |
| GO:0014704 intercalated disc | IDA PMID:22889254 Detection of genomic deletions of PKP2 in arrhythmogenic rig... | ACCEPT | Summary: The original PMID and clinical cardiac context are authenticated, but the target-specific full localization experiment was not recovered. Reason: The original PMID and clinical cardiac context are authenticated, but the target-specific full localization experiment was not recovered. DSP residence at intercalated discs is independently established, including the primary multi-species immunoelectron study that explicitly includes human tissue. Retain the curator-supported location; do not infer that a paper centered on PKP2 or DSG2 omitted DSP. |
| GO:0014704 intercalated disc | IDA PMID:23381804 Mutated desmoglein-2 proteins are incorporated into desmosom... | ACCEPT | Summary: The original PMID and clinical cardiac context are authenticated, but the target-specific full localization experiment was not recovered. Reason: The original PMID and clinical cardiac context are authenticated, but the target-specific full localization experiment was not recovered. DSP residence at intercalated discs is independently established, including the primary multi-species immunoelectron study that explicitly includes human tissue. Retain the curator-supported location; do not infer that a paper centered on PKP2 or DSG2 omitted DSP. |
| GO:0014704 intercalated disc | IEA GO_REF:0000120 | ACCEPT | Summary: The exact mouse Dsp donor and the official ARBA/orthology source map to intercalated disc. Reason: The exact mouse Dsp donor and the official ARBA/orthology source map to intercalated disc. Recovered mouse immunoelectron Results and an authenticated primary abstract explicitly including human tissue support the conserved compartment. The source is retained as inferred evidence, not relabelled as a direct human experiment. Propagation Review Root cause: NO FAILURE CORE |
| GO:0014704 intercalated disc | ISS GO_REF:0000024 | ACCEPT | Summary: The exact mouse Dsp donor and the official ARBA/orthology source map to intercalated disc. Reason: The exact mouse Dsp donor and the official ARBA/orthology source map to intercalated disc. Recovered mouse immunoelectron Results and an authenticated primary abstract explicitly including human tissue support the conserved compartment. The source is retained as inferred evidence, not relabelled as a direct human experiment. Propagation Review Root cause: NO FAILURE CORE |
| GO:0016323 basolateral plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The literal mouse donor study uses differentiating HNF-3beta-transfected embryonic stem cells and explicitly co-localizes DSP with basolateral-marker oatp1; the abstract notes broad membrane distributions. Reason: The literal mouse donor study uses differentiating HNF-3beta-transfected embryonic stem cells and explicitly co-localizes DSP with basolateral-marker oatp1; the abstract notes broad membrane distributions. Retain this contextual basolateral pool without treating the source as direct human hepatocyte localization or excluding other membrane domains. Propagation Review Root cause: NO FAILURE NON CORE |
| GO:0018149 peptide cross-linking | IDA PMID:10908733 Small proline-rich protein 1 is the major component of the c... | MARK AS OVER ANNOTATED | Summary: The current term requires formation of a covalent cross-link between or within protein chains. Reason: The current term requires formation of a covalent cross-link between or within protein chains. The recovered original detects a DSP peptide after digestion of a highly resistant cornified-envelope preparation; it does not recover a joined DSP cross-link peptide or establish DSP as the catalyst, template or cofactor that performs cross-link formation. The study discusses transglutaminases as the cross-linking enzymes and DSP as incorporated structural material. Thus the experiment is real and supports envelope incorporation, but assigning the cross-linking process itself to DSP overstates the demonstrated role. This is not a wrong-gene or false-experiment claim. Supporting Evidence: |
| GO:0021532 neural tube patterning | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Mouse neuroepithelial integrity is supported; regional patterning is over-specific. Reason: PMID:11222147 reports mouse tube formation/closure followed by collapse, with recognizable neuroepithelial layers retained. GO:0021532 requires regionalization. The observed structural developmental contribution does not establish that specific process; retain the biological context while marking the term over-annotated. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH |
| GO:0021532 neural tube patterning | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Mouse neuroepithelial integrity is supported; regional patterning is over-specific. Reason: PMID:11222147 reports mouse tube formation/closure followed by collapse, with recognizable neuroepithelial layers retained. GO:0021532 requires regionalization. The observed structural developmental contribution does not establish that specific process; retain the biological context while marking the term over-annotated. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH |
| GO:0030054 cell junction | IDA GO_REF:0000052 | MODIFY | Summary: The actual HPA ICC/IF record gives supported cell-junction localization in A-431 cells. Reason: The actual HPA ICC/IF record gives supported cell-junction localization in A-431 cells. It does not itself resolve desmosomal ultrastructure. Independent human DSP plaque/localization experiments establish the more informative desmosome pool, used as a gene-level refinement while preserving the HPA assay resolution and nonexclusive pools. Proposed replacements: desmosome Supporting Evidence: GO_REF:0000052 https://www.proteinatlas.org/ENSG00000096696-DSP/subcellular |
| GO:0030057 desmosome | IDA PMID:18343367 P120-catenin is a novel desmoglein 3 interacting partner: id... | ACCEPT | Summary: The original is authenticated, but its full DSP-specific imaging experiment was not recovered. Reason: The original is authenticated, but its full DSP-specific imaging experiment was not recovered. Independent human DSP plaque assembly and epithelial localization directly establish desmosome residence. Retain the curator-supported assertion; the paper's emphasis on Dsg3/p120 is not evidence that DSP was not also visualized. |
| GO:0030057 desmosome | IDA PMID:20859650 E-cadherin and plakoglobin recruit plakophilin3 to the cell ... | ACCEPT | Summary: The recovered original directly shows endogenous human DSP border staining in control HaCaT/HCT116 cells, its loss or cytoplasmic redistribution after PKP3 depletion, and restored border recruitment after PKP3 rescue. Reason: The recovered original directly shows endogenous human DSP border staining in control HaCaT/HCT116 cells, its loss or cytoplasmic redistribution after PKP3 depletion, and restored border recruitment after PKP3 rescue. These are positive desmosomal localization/assembly observations; the perturbation is PKP3, not an unreported DSP knockout. Supporting Evidence: |
| GO:0030057 desmosome | IDA PMID:25733715 GSK3- and PRMT-1-dependent modifications of desmoplakin cont... | ACCEPT | Summary: The original human DSP constructs and cellular imaging establish desmosomal residence. Reason: The original human DSP constructs and cellular imaging establish desmosomal residence. The R2834H variant alters IF association and border recruitment; FRAP did not establish increased instability of already assembled mature junctions. Retain the location without turning every mutant phenotype into a defect in mature-desmosome maintenance. Supporting Evidence: |
| GO:0030057 desmosome | IDA PMID:28891468 Epidermal Growth Factor Receptor neddylation is regulated by... | ACCEPT | Summary: Endogenous human keratinocyte DSP localization and the DSG1/COP9 study's DSP interaction/perturbation data support the desmosomal pool. Reason: Endogenous human keratinocyte DSP localization and the DSG1/COP9 study's DSP interaction/perturbation data support the desmosomal pool. The catalytic deneddylation activity belongs to COP9, not DSP; this does not diminish the positive localization assertion. Supporting Evidence: |
| GO:0030057 desmosome | IEA GO_REF:0000120 | ACCEPT | Summary: The mouse/rat donor and official desmosomal location mappings are consistent with independently established human DSP plaque residence. Reason: The mouse/rat donor and official desmosomal location mappings are consistent with independently established human DSP plaque residence. Preserve every source accession and inferred evidence code. Cross-species mapping supports the gene-level compartment, without proving functional equivalence among all three natural DSP products. Propagation Review Root cause: NO FAILURE CORE |
| GO:0030057 desmosome | ISS GO_REF:0000024 | ACCEPT | Summary: The mouse/rat donor and official desmosomal location mappings are consistent with independently established human DSP plaque residence. Reason: The mouse/rat donor and official desmosomal location mappings are consistent with independently established human DSP plaque residence. Preserve every source accession and inferred evidence code. Cross-species mapping supports the gene-level compartment, without proving functional equivalence among all three natural DSP products. Propagation Review Root cause: NO FAILURE CORE |
| GO:0030216 keratinocyte differentiation | IDA PMID:10908733 Small proline-rich protein 1 is the major component of the c... | KEEP AS NON CORE | Summary: The recovered original directly examines human differentiated oral keratinocytes and incorporates DSP-derived material into their cornified envelopes. Reason: The recovered original directly examines human differentiated oral keratinocytes and incorporates DSP-derived material into their cornified envelopes. This supports a structural differentiation context. It does not demonstrate DSP as the transglutaminase or isolate a DSP-specific differentiation-regulatory pathway; retain the contextual process rather than infer a new enzyme activity. Supporting Evidence: |
| GO:0030424 axon | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: The literal mouse donor is supported by the primary nerve-regeneration abstract: DSP is upregulated in motoneurons after sciatic nerve injury, associates with a N-cadherin/JUP/vimentin complex and affects axonal growth-front localization and repair after conditional deletion. Reason: The literal mouse donor is supported by the primary nerve-regeneration abstract: DSP is upregulated in motoneurons after sciatic nerve injury, associates with a N-cadherin/JUP/vimentin complex and affects axonal growth-front localization and repair after conditional deletion. Preserve this positive specialized axonal pool, with the mouse injury context explicit and no inferred universal neuronal location. Propagation Review Root cause: NO FAILURE NON CORE |
| GO:0030424 axon | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The literal mouse donor is supported by the primary nerve-regeneration abstract: DSP is upregulated in motoneurons after sciatic nerve injury, associates with a N-cadherin/JUP/vimentin complex and affects axonal growth-front localization and repair after conditional deletion. Reason: The literal mouse donor is supported by the primary nerve-regeneration abstract: DSP is upregulated in motoneurons after sciatic nerve injury, associates with a N-cadherin/JUP/vimentin complex and affects axonal growth-front localization and repair after conditional deletion. Preserve this positive specialized axonal pool, with the mouse injury context explicit and no inferred universal neuronal location. Propagation Review Root cause: NO FAILURE NON CORE |
| GO:0032880 regulation of protein localization | IEA GO_REF:0000107 | MODIFY | Summary: The exact mouse donor paper directly shows DP-dependent ninein recruitment to cell-cell borders in differentiating epidermis and rescue by full-length or head-plus-rod DSP, while the head alone fails. Reason: The exact mouse donor paper directly shows DP-dependent ninein recruitment to cell-cell borders in differentiating epidermis and rescue by full-length or head-plus-rod DSP, while the head alone fails. A biochemical ninein–DSP interface was not resolved. Together with independently measured human EB1/Cx43 junction targeting, this supports the more informative positive regulation of protein localization to cell-cell junction. The refinement preserves the localization-regulatory role without claiming DSP catalyzes transport. Propagation Review Root cause: TERM SCOPING PROBLEM Proposed replacements: positive regulation of protein localization to cell-cell junction |
| GO:0032880 regulation of protein localization | ISS GO_REF:0000024 | MODIFY | Summary: The exact mouse donor paper directly shows DP-dependent ninein recruitment to cell-cell borders in differentiating epidermis and rescue by full-length or head-plus-rod DSP, while the head alone fails. Reason: The exact mouse donor paper directly shows DP-dependent ninein recruitment to cell-cell borders in differentiating epidermis and rescue by full-length or head-plus-rod DSP, while the head alone fails. A biochemical ninein–DSP interface was not resolved. Together with independently measured human EB1/Cx43 junction targeting, this supports the more informative positive regulation of protein localization to cell-cell junction. The refinement preserves the localization-regulatory role without claiming DSP catalyzes transport. Propagation Review Root cause: TERM SCOPING PROBLEM Proposed replacements: positive regulation of protein localization to cell-cell junction |
| GO:0042060 wound healing | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The genuine PAINT IBD at PTN002753757 propagates through the verified DSP target path, with experimental grounding among other plakin descendants. Reason: The genuine PAINT IBD at PTN002753757 propagates through the verified DSP target path, with experimental grounding among other plakin descendants. There is no established target-specific loss that overturns this ancestral judgment. Retain wound healing as a tissue-repair context rather than a separate DSP biochemical function; donor number is not used as a confidence surrogate. The fixed PAINT audit preserves the literal IBD, target lineage, descendant donor identities and absence of an intervening target-path IRD; donor count is not used to overrule the curator. Propagation Review Root cause: NO FAILURE NON CORE |
| GO:0043588 skin development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The literal PAINT assertion at PTN002753793 includes the human DSP descendant and target experimental grounding. Reason: The literal PAINT assertion at PTN002753793 includes the human DSP descendant and target experimental grounding. Human skin-fragility genetics and mouse epidermal loss/rescue support a developmental tissue-integrity role. Retain it outside the immediate structural unit without calling self-grounding circular or claiming a separate skin-patterning enzyme. The fixed PAINT audit preserves the literal IBD, target lineage, descendant donor identities and absence of an intervening target-path IRD; donor count is not used to overrule the curator. Propagation Review Root cause: NO FAILURE NON CORE |
| GO:0045104 intermediate filament cytoskeleton organization | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT IBD at PTN002753757 is ancestral to DSP with no intervening target-path loss. Reason: The PAINT IBD at PTN002753757 is ancestral to DSP with no intervening target-path loss. The current process definition includes arranging IF-associated proteins, not merely polymerizing filament monomers. DSP physically links IFs to junctions, and mouse deletion directly disrupts the network before overt tissue failure, supporting this inherited structural process. The fixed PAINT audit preserves the literal IBD, target lineage, descendant donor identities and absence of an intervening target-path IRD; donor count is not used to overrule the curator. Propagation Review Root cause: NO FAILURE CORE |
| GO:0045104 intermediate filament cytoskeleton organization | IEA GO_REF:0000002 | ACCEPT | Summary: The plakin-family InterPro mapping is independently corroborated for DSP by its human tail–IF interaction and the conserved IF-network defects after Dsp loss. Reason: The plakin-family InterPro mapping is independently corroborated for DSP by its human tail–IF interaction and the conserved IF-network defects after Dsp loss. The term includes arrangement of associated cytoskeletal components. This is a structural organization function, not inferred IF monomer polymerization or direct microtubule binding. Propagation Review Root cause: NO FAILURE CORE |
| GO:0045109 intermediate filament organization | IEA GO_REF:0000107 | ACCEPT | Summary: The exact mouse Dsp donor and the cardiac source support IF organization. Reason: The exact mouse Dsp donor and the cardiac source support IF organization. The current definition concerns spatial distribution, and the independently recovered mouse loss-of-function study directly shows collapse of the keratin network and loss of junctional anchorage. Human IF interaction corroborates the conserved mechanism; preserve the original organism/source identity. Propagation Review Root cause: NO FAILURE CORE |
| GO:0045109 intermediate filament organization | ISS PMID:16917092 Desmosomal dysfunction due to mutations in desmoplakin cause... | ACCEPT | Summary: The exact mouse Dsp donor and the cardiac source support IF organization. Reason: The exact mouse Dsp donor and the cardiac source support IF organization. The current definition concerns spatial distribution, and the independently recovered mouse loss-of-function study directly shows collapse of the keratin network and loss of junctional anchorage. Human IF interaction corroborates the conserved mechanism; preserve the original organism/source identity. Propagation Review Root cause: NO FAILURE CORE |
| GO:0045596 negative regulation of cell differentiation | IMP PMID:17475244 Increased keratinocyte proliferation initiated through downr... | UNDECIDED | Summary: The authenticated PMID:17475244 abstract reports DSP knockdown, increased proliferation/G1–S progression, ERK/Akt phosphorylation and reductions in other junctional proteins. Reason: The authenticated PMID:17475244 abstract reports DSP knockdown, increased proliferation/G1–S progression, ERK/Akt phosphorylation and reductions in other junctional proteins. The target-specific full differentiation experiments were not recovered through bounded access attempts. These accessible results do not resolve the literal negative regulation of cell differentiation assertion. Defer rather than infer that the full paper lacked such an assay or that the curator made an error. Supporting Evidence: |
| GO:0045618 positive regulation of keratinocyte differentiation | IMP PMID:28891468 Epidermal Growth Factor Receptor neddylation is regulated by... | KEEP AS NON CORE | Summary: The recovered human keratinocyte study gives positive DSP-dependent EGFR handling: DSP depletion alters EGFR neddylation/ubiquitination and delays border clearance. Reason: The recovered human keratinocyte study gives positive DSP-dependent EGFR handling: DSP depletion alters EGFR neddylation/ubiquitination and delays border clearance. Much of the direct differentiation-marker and rescue analysis is performed on COPS3, so the DSP differentiation role is retained as a contextual inference within the junctional signaling mechanism, not recast as a directly measured DSP deneddylase or as an all-DSP version of the COPS3 experiments. Supporting Evidence: |
| GO:0045786 negative regulation of cell cycle | IMP PMID:17475244 Increased keratinocyte proliferation initiated through downr... | KEEP AS NON CORE | Summary: The authenticated primary abstract reports increased proliferation and G1–S progression after DSP RNA interference in human HaCaT cells, together with ERK/Akt changes. Reason: The authenticated primary abstract reports increased proliferation and G1–S progression after DSP RNA interference in human HaCaT cells, together with ERK/Akt changes. This is positive context for restraint of cell-cycle progression; full source-specific Methods were unavailable. Retain the contextual consequence without assigning a cell-cycle catalytic activity to DSP. Supporting Evidence: |
| GO:0050821 protein stabilization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse donor has positive protein-stability evidence from the recovered Cx43 study: DSP depletion reduces Cx43 lifetime and favors lysosomal turnover, with Ras/ERK-dependent effects and rescue. Reason: The mouse donor has positive protein-stability evidence from the recovered Cx43 study: DSP depletion reduces Cx43 lifetime and favors lysosomal turnover, with Ras/ERK-dependent effects and rescue. This supports contextual stabilization through junctional organization, distinct from direct protease inhibition or a universal stabilization function. Human DSP junction-targeting results corroborate the broader mechanism. Propagation Review Root cause: NO FAILURE NON CORE |
| GO:0050821 protein stabilization | IMP PMID:17475244 Increased keratinocyte proliferation initiated through downr... | KEEP AS NON CORE | Summary: The primary abstract reports reduced levels of other desmosomal and adherens-junction proteins after human HaCaT DSP depletion. Reason: The primary abstract reports reduced levels of other desmosomal and adherens-junction proteins after human HaCaT DSP depletion. Full source-specific turnover measurements were not recovered, so none are invented. Independently recovered Cx43 decay/rescue experiments support a genuine gene-level stabilization role in a defined junctional context; retain the existing claim without treating altered abundance alone as a measured half-life. |
| GO:0050821 protein stabilization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The mouse donor has positive protein-stability evidence from the recovered Cx43 study: DSP depletion reduces Cx43 lifetime and favors lysosomal turnover, with Ras/ERK-dependent effects and rescue. Reason: The mouse donor has positive protein-stability evidence from the recovered Cx43 study: DSP depletion reduces Cx43 lifetime and favors lysosomal turnover, with Ras/ERK-dependent effects and rescue. This supports contextual stabilization through junctional organization, distinct from direct protease inhibition or a universal stabilization function. Human DSP junction-targeting results corroborate the broader mechanism. Propagation Review Root cause: NO FAILURE NON CORE |
| GO:0061028 establishment of endothelial barrier | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The exact mouse donor is the extraembryonic-rescue study. Reason: The exact mouse donor is the extraembryonic-rescue study. Its abstract explicitly describes non-desmosomal endothelial junctions containing DP, JUP and VE-cadherin and severe vascular defects after Dsp loss. Retain the positive endothelial-barrier context with this organism/cell-type scope; it is not merely extrapolated from skin desmosomes or evidence for an independent endothelial enzyme. Propagation Review Root cause: NO FAILURE NON CORE |
| GO:0061028 establishment of endothelial barrier | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The exact mouse donor is the extraembryonic-rescue study. Reason: The exact mouse donor is the extraembryonic-rescue study. Its abstract explicitly describes non-desmosomal endothelial junctions containing DP, JUP and VE-cadherin and severe vascular defects after Dsp loss. Retain the positive endothelial-barrier context with this organism/cell-type scope; it is not merely extrapolated from skin desmosomes or evidence for an independent endothelial enzyme. Propagation Review Root cause: NO FAILURE NON CORE |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: The recovered original Table 1 directly lists DSP with ten unique peptides and 16 spectra in a low-density human urinary membrane preparation enriched for exosomes. Reason: The recovered original Table 1 directly lists DSP with ten unique peptides and 16 spectra in a low-density human urinary membrane preparation enriched for exosomes. The Methods describe differential centrifugation, DTT treatment and protein-identity filtering. This is positive fraction detection, not an inferred contaminant, but does not establish an exosome-specific DSP function, vesicle topology or uniquely identified modern isoform. |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: Genuine supplemental Table 2 lists DSP/IPI00013933.2 at Excel row 176 with 16 sequences, 16 spectra and 8.3% coverage in the human parotid exosome preparation. Reason: Genuine supplemental Table 2 lists DSP/IPI00013933.2 at Excel row 176 with 16 sequences, 16 spectra and 8.3% coverage in the human parotid exosome preparation. The original describes ductal collection, differential centrifugation, at least two peptides per protein group and independent vesicle-marker assessment. Retain this positive fraction localization while distinguishing it from a DSP-specific intravesicular protection test or a demonstrated vesicle-biogenesis role. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | UNDECIDED | Summary: The original PMID and B-cell exosome study are authenticated, but the DSP-specific target table and full original were not recovered. Reason: The original PMID and B-cell exosome study are authenticated, but the DSP-specific target table and full original were not recovered. Saved .xls-labelled routes are HTML challenge/error payloads, not spreadsheets, and are not used as target evidence. The independent urinary and parotid DSP detections make extracellular-vesicle association plausible but do not verify this B-cell source claim. Preserve the assertion pending source access; no contamination or signal-peptide argument is made. |
| GO:0086073 bundle of His cell-Purkinje myocyte adhesion involved in cell communication | IMP PMID:12373648 Mutation in human desmoplakin domain binding to plakoglobin ... | MARK AS OVER ANNOTATED | Summary: The current GO definition requires attachment between a bundle-of-His cell and a Purkinje myocyte that enables their communication. Reason: The current GO definition requires attachment between a bundle-of-His cell and a Purkinje myocyte that enables their communication. The recovered human S299R primary study reports clinical cardiac phenotyping, ECG/Holter findings, linkage and sequencing, not a measured interaction between those cell types. The proposed S299 phosphorylation/JUP mechanism is inferential. Clinical arrhythmia is real but does not establish this precise anatomical communication process; retain the source identity while marking the scope as excessive. Supporting Evidence: |
| GO:0086083 cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication | IC PMID:12373648 Mutation in human desmoplakin domain binding to plakoglobin ... | MARK AS OVER ANNOTATED | Summary: This IC claim is based on GO:0086073 and its current definition requires protein binding that connects a bundle-of-His cell with a Purkinje myocyte. Reason: This IC claim is based on GO:0086073 and its current definition requires protein binding that connects a bundle-of-His cell with a Purkinje myocyte. The recovered clinical/genetic source does not assay that interface, and its proposed JUP-binding mechanism is not a measured binding result. DSP has independently established plaque-partner binding, but that does not establish the His–Purkinje-specific activity. The problem is the inferred scope, not falsity of the patient observations. Propagation Review Root cause: TERM SCOPING PROBLEM Supporting Evidence: |
| GO:0086091 regulation of heart rate by cardiac conduction | IMP PMID:12373648 Mutation in human desmoplakin domain binding to plakoglobin ... | KEEP AS NON CORE | Summary: The recovered human S299R clinical/genetic study reports arrhythmic cardiac disease and conduction-related phenotyping. Reason: The recovered human S299R clinical/genetic study reports arrhythmic cardiac disease and conduction-related phenotyping. Retain a contextual cardiac-conduction/rhythm role associated with disrupted DSP junctional integrity. It does not establish a direct ion-channel or pacemaker activity, nor the specific His–Purkinje contact asserted by the separate over-scoped annotations. Supporting Evidence: |
| GO:0090136 epithelial cell-cell adhesion | IMP PMID:26604139 Dominant de novo DSP mutations cause erythrokeratodermia-car... | ACCEPT | Summary: The recovered human EKC study combines patient skin pathology/ultrastructure with DSP-mutant cellular analyses: reduced junctional components, widened intercellular spaces and altered junction assembly support an epithelial-adhesion function. Reason: The recovered human EKC study combines patient skin pathology/ultrastructure with DSP-mutant cellular analyses: reduced junctional components, widened intercellular spaces and altered junction assembly support an epithelial-adhesion function. Engineered DPII and human tissue observations are kept distinct; no equivalence of every natural DSP product is assumed. Supporting Evidence: |
| GO:0090136 epithelial cell-cell adhesion | IMP PMID:27892606 SVEP1 plays a crucial role in epidermal differentiation. | ACCEPT | Summary: The recovered original actually includes DSP siRNA as a positive control in the human foreskin-keratinocyte dispase assay and observes reduced mechanical cohesion. Reason: The recovered original actually includes DSP siRNA as a positive control in the human foreskin-keratinocyte dispase assay and observes reduced mechanical cohesion. The paper's emphasis on SVEP1 does not make the DSP result a misattribution. Preserve the original acts_upstream_of_or_within qualifier rather than silently upgrading its relationship. Supporting Evidence: |
| GO:0097110 scaffold protein binding | IPI PMID:10852826 Interaction of plakophilins with desmoplakin and intermediat... | ACCEPT | Summary: PKP1 is a desmosomal scaffold that organizes plaque partners, and its association with DSP is supported by the original biochemical study and independently recovered binary DSP-NTP/PKP1-head interaction. Reason: PKP1 is a desmosomal scaffold that organizes plaque partners, and its association with DSP is supported by the original biochemical study and independently recovered binary DSP-NTP/PKP1-head interaction. The scaffold-binding assertion describes this recognition, not transfer of the partner's other signaling or translation activities to DSP. Full target-specific Methods of PMID:10852826 were not recovered; the independent original supports the gene-level class. |
| GO:0098609 cell-cell adhesion | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT IBD at PTN002753793 propagates through the verified DSP path and includes target experimental grounding. Reason: The PAINT IBD at PTN002753793 propagates through the verified DSP path and includes target experimental grounding. Human DSP depletion/mutant mechanical-cohesion assays and conserved desmosomal linkage support a direct structural contribution to cell-cell adhesion. The self-donor is valid evidence, not a circularity diagnosis. The fixed PAINT audit preserves the literal IBD, target lineage, descendant donor identities and absence of an intervening target-path IRD; donor count is not used to overrule the curator. Propagation Review Root cause: NO FAILURE CORE |
| GO:0098609 cell-cell adhesion | IMP PMID:25733715 GSK3- and PRMT-1-dependent modifications of desmoplakin cont... | ACCEPT | Summary: The original dispase assay measures weaker intercellular cohesion in DSP R2834H-expressing human epithelial sheets, with wild-type and phosphorylation-mutant comparisons. Reason: The original dispase assay measures weaker intercellular cohesion in DSP R2834H-expressing human epithelial sheets, with wild-type and phosphorylation-mutant comparisons. Live imaging also shows altered recruitment kinetics. These positive assays support structural cell-cell adhesion without attributing the phenotype solely to mature-junction instability or declaring DSP an adhesion receptor. Supporting Evidence: |
| GO:0098609 cell-cell adhesion | ISS GO_REF:0000024 | ACCEPT | Summary: The exact mouse Dsp donor is supported by primary loss/rescue studies in epidermis and embryos; human DSP perturbation and mechanical-cohesion assays independently establish the same direct structural adhesion contribution. Reason: The exact mouse Dsp donor is supported by primary loss/rescue studies in epidermis and embryos; human DSP perturbation and mechanical-cohesion assays independently establish the same direct structural adhesion contribution. Retain the inferred source and species boundary rather than replacing it with a manufactured experimental row. Propagation Review Root cause: NO FAILURE CORE |
| GO:0098911 regulation of ventricular cardiac muscle cell action potential | IMP PMID:12373648 Mutation in human desmoplakin domain binding to plakoglobin ... | MARK AS OVER ANNOTATED | Summary: The current term requires modulation of ventricular-cardiomyocyte action-potential creation, propagation or termination. Reason: The current term requires modulation of ventricular-cardiomyocyte action-potential creation, propagation or termination. The recovered S299R study measures clinical arrhythmia/conduction phenotypes and genetic segregation, not ventricular-cell electrophysiology or a DSP-dependent action-potential mechanism. Those findings justify cardiac relevance but not this precise physiological process. Mark the scope as excessive without denying the disease association or claiming the patient measurements were false. Supporting Evidence: |
| GO:0101003 ficolin-1-rich granule membrane | TAS Reactome:R-HSA-6800426 | UNDECIDED | Summary: The exact current Reactome model contains human DSP/P15924 as a hasMember of set 6800437 at ficolin-1-rich granule membrane, with entity 6801396 and nominal residues 1–2871. Reason: The exact current Reactome model contains human DSP/P15924 as a hasMember of set 6800437 at ficolin-1-rich granule membrane, with entity 6801396 and nominal residues 1–2871. This is a positive curated assertion, but the underlying PMID:23650620 DSP-specific fraction table was not accessible in the bounded source audit. It remains unresolved whether the measurement supports this narrow neutrophil organelle pool; known junctional DSP and lack of a secretion signal are not counterevidence. Preserve the TAS assertion and uncertainty. Supporting Evidence: Reactome:R-HSA-6800426 file:human/DSP/DSP-evidence/reactome-paths.yaml |
| GO:0150105 protein localization to cell-cell junction | IEA GO_REF:0000107 | ACCEPT | Summary: The literal mouse Dsp donor supports localization of junctional partners, and recovered mouse ninein rescue plus human EB1/Cx43 experiments establish a physical recruitment/retention contribution by DSP. Reason: The literal mouse Dsp donor supports localization of junctional partners, and recovered mouse ninein rescue plus human EB1/Cx43 experiments establish a physical recruitment/retention contribution by DSP. Retain participation in protein localization to the cell-cell junction; the target supplies a spatial scaffold rather than motor or enzymatic transport activity. The imported localization-process claim is not silently replaced by a cross-branch regulatory term. Propagation Review Root cause: NO FAILURE CORE |
| GO:0150105 protein localization to cell-cell junction | ISS PMID:16917092 Desmosomal dysfunction due to mutations in desmoplakin cause... | ACCEPT | Summary: The literal mouse Dsp donor supports localization of junctional partners, and recovered mouse ninein rescue plus human EB1/Cx43 experiments establish a physical recruitment/retention contribution by DSP. Reason: The literal mouse Dsp donor supports localization of junctional partners, and recovered mouse ninein rescue plus human EB1/Cx43 experiments establish a physical recruitment/retention contribution by DSP. Retain participation in protein localization to the cell-cell junction; the target supplies a spatial scaffold rather than motor or enzymatic transport activity. The imported localization-process claim is not silently replaced by a cross-branch regulatory term. Propagation Review Root cause: NO FAILURE CORE |
| GO:1903829 positive regulation of protein localization | IEA GO_REF:0000120 | MODIFY | Summary: The literal mouse donor PMID:29959233 directly measures junctional Cx43 loss after DSP depletion, with engineered human DPII rescue in rat cardiomyocytes and separate mouse cardiac/epidermal observations. Reason: The literal mouse donor PMID:29959233 directly measures junctional Cx43 loss after DSP depletion, with engineered human DPII rescue in rat cardiomyocytes and separate mouse cardiac/epidermal observations. The rat donor PMID:25225338 additionally grounds junctional delivery. These results support the more specific positive regulation of protein localization to cell-cell junction. Human, rat and mouse measurements are kept distinct, and the historical engineered DPII construct is not declared identical to a modern natural sequence without alignment. Propagation Review Root cause: TERM SCOPING PROBLEM Proposed replacements: positive regulation of protein localization to cell-cell junction |
| GO:1903829 positive regulation of protein localization | IMP PMID:25225338 Disease mutations in desmoplakin inhibit Cx43 membrane targe... | MODIFY | Summary: The recovered original directly shows human keratinocyte Cx43 junction targeting and communication defects after DSP loss or EB1-binding-deficient DSP mutations, with engineered wild-type DPII rescue and EB1-dependent separation of function. Reason: The recovered original directly shows human keratinocyte Cx43 junction targeting and communication defects after DSP loss or EB1-binding-deficient DSP mutations, with engineered wild-type DPII rescue and EB1-dependent separation of function. The measured endpoint is localization at cell-cell junctions, so GO:0150107 is the verified more specific child of the original positive-localization term. This does not claim that DSP is a transport motor, a direct microtubule binder or a gap-junction channel. Proposed replacements: positive regulation of protein localization to cell-cell junction |
| GO:1903829 positive regulation of protein localization | ISS GO_REF:0000024 | MODIFY | Summary: The literal mouse donor PMID:29959233 directly measures junctional Cx43 loss after DSP depletion, with engineered human DPII rescue in rat cardiomyocytes and separate mouse cardiac/epidermal observations. Reason: The literal mouse donor PMID:29959233 directly measures junctional Cx43 loss after DSP depletion, with engineered human DPII rescue in rat cardiomyocytes and separate mouse cardiac/epidermal observations. The rat donor PMID:25225338 additionally grounds junctional delivery. These results support the more specific positive regulation of protein localization to cell-cell junction. Human, rat and mouse measurements are kept distinct, and the historical engineered DPII construct is not declared identical to a modern natural sequence without alignment. Propagation Review Root cause: TERM SCOPING PROBLEM Proposed replacements: positive regulation of protein localization to cell-cell junction |
| GO:2001214 positive regulation of vasculogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The literal mouse donor study rescues extraembryonic Dsp loss and reveals embryonic vascular defects, including non-desmosomal endothelial junctions containing DSP/JUP/VE-cadherin. Reason: The literal mouse donor study rescues extraembryonic Dsp loss and reveals embryonic vascular defects, including non-desmosomal endothelial junctions containing DSP/JUP/VE-cadherin. Retain the contextual positive vasculogenesis role supported by the curated donor and primary abstract. It is not a direct human angiogenic-signal assay or a distinct biochemical core. Propagation Review Root cause: NO FAILURE NON CORE |
| GO:2001214 positive regulation of vasculogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The literal mouse donor study rescues extraembryonic Dsp loss and reveals embryonic vascular defects, including non-desmosomal endothelial junctions containing DSP/JUP/VE-cadherin. Reason: The literal mouse donor study rescues extraembryonic Dsp loss and reveals embryonic vascular defects, including non-desmosomal endothelial junctions containing DSP/JUP/VE-cadherin. Retain the contextual positive vasculogenesis role supported by the curated donor and primary abstract. It is not a direct human angiogenic-signal assay or a distinct biochemical core. Propagation Review Root cause: NO FAILURE NON CORE |
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Download this section (compressed HTML)Q: How do the three natural rod-splice products differ in plaque mechanics, intermediate-filament linkage and EB1-dependent connexin targeting at endogenous abundance?
Q: Under which cell states is nuclear desmoplakin recruited to telomeres, and does its TRF2-dependent association alter telomere maintenance independently of junctional stress?
Q: What target-specific measurements support DSP in B-cell exosomes and ficolin-rich neutrophil granule membranes, and do these pools have a biological role distinct from junctional incorporation?
Experiment: Compare sequence-verified DPI, DPII and DSPIa at matched endogenous expression in DSP-deficient human keratinocytes and cardiomyocytes. Measure plaque recruitment, intermediate-filament anchorage, mechanical cohesion and EB1-dependent Cx43 targeting with rescue and expression controls.
Hypothesis: Natural rod-splice products differ in junctional mechanical coupling or trafficking while retaining terminal binding regions.
Type: Isoform-resolved rescue and cell mechanics
Experiment: Use endogenous localization tags and compartment-restricted rescue with matched expression to distinguish nuclear recruitment, TRF2 association and telomere damage from secondary changes in adhesion, cell cycle or DNA damage.
Hypothesis: The nuclear DSP phenotype depends on a separable recruitment mechanism rather than secondary junctional disruption.
Type: Compartment-resolved perturbation and rescue
Experiment: Combine target-specific peptides with orthogonal antibody validation, fraction-purity controls and protease protection with and without detergent in the relevant human cell preparations. Keep intracellular carryover and surface-associated material distinguishable from protected vesicle cargo.
Hypothesis: DSP detected in extracellular or granule fractions is a reproducible physical pool with definable topology.
Type: Targeted proteomics and biochemical topology
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