Dystonin is a plakin-family cytolinker whose alternative products connect cytoskeletal networks with cellular attachment structures and intracellular transport machinery. Epithelial BP230 links keratin intermediate filaments to hemidesmosomal membrane proteins and supports keratinocyte polarity and directional migration. Larger muscle and neuronal forms contain different combinations of filament-binding domains. Their functions include structural coupling at muscle Z-discs, microtubule association and regulation, and dynactin-associated retrograde transport in neurons. Product-specific domain composition and localization give these forms distinct functional capacities.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000226 microtubule cytoskeleton organization | IEA GO_REF:0000117 | ACCEPT | Summary: DST organizes microtubule networks through product-specific cytoskeletal interactions. Reason: The electronic assertion agrees with the direct microtubule-binding and calcium-responsive tail experiments in PMID:22995871 and the conserved neuronal microtubule stabilization described in PMID:10428034. The latter source is abstract-only here. This does not assign all nine natural products the same domain composition or function. The ARBA rule was retrieved, but target membership in all FunFam conditions was not independently resolved. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028425 UNRESOLVED Actual rule and target domains/lineage were retrieved. Precise membership in all FunFam conditions was not independently resolved; biological disposition rests additionally on the cited primary/curated evidence, not an invented rule failure. |
| GO:0001725 stress fiber | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Stress-fiber localization is a contextual, N-terminal-product-dependent pool. Reason: The mouse Dst record and the authentic PMID:14576348 abstract report stress-fiber alignment of an antibody-defined Bpag1a/b pool and an N-terminal fusion in C2C12 myoblasts. This supports the positive location while retaining the organism and construct limits. Historical isoform numbers are not equated with current short human products. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0501 SUPPORTS TRANSFER Source mapping is retained; independent target or donor evidence and its scope are explained in the row rationale. |
| GO:0005178 integrin binding | IPI PMID:11375975 The hemidesmosomal protein bullous pemphigoid antigen 1 and ... | ACCEPT | Summary: Epithelial BP230 binds the cytoplasmic region of integrin beta4. Reason: PMID:11375975 directly tests human BPAG1 and integrin beta4 fragments in yeast, with beta4 C-terminal sequences recovered by the human keratinocyte-library screen. The independently read PMID:10637308 supports complementary BP230/beta4 contacts. These interactions help anchor the epithelial hemidesmosomal cytoskeleton; they do not establish identical binding by every DST product. |
| GO:0005198 structural molecule activity | IBA GO_REF:0000033 | MODIFY | Summary: The conserved structural function can be specified as a cytoskeletal constituent. Reason: The literal PTN002753757 IBD is above the sequence-authenticated human DST leaf. Human epithelial interaction studies and product-specific microtubule experiments establish a structural cytolinker, supporting GO:0005200 rather than an unspecified structural molecule. This refinement covers cytoskeletal integrity without imposing an autonomous motor activity or converting every positive pair into an adaptor function. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002753757 SUPPORTS TRANSFER Literal IBD, aligned target sequence and complete target-to-root path authenticated in PTHR23169; the node is ancestral to human DST. The structural function is refined using independent target evidence. Proposed replacements: structural constituent of cytoskeleton |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Calcium binding is a regulatory domain property rather than the whole cytolinker function. Reason: The mapped EF-hand domain and PMID:22995871 support a calcium-responsive tail whose EF-hand mutations alter the switch between EB1 association and microtubule decoration. The read experiments do not provide a direct calcium-affinity measurement or show this property for all natural products. Retain the domain-based annotation as a non-core regulatory feature, without inferring calcium transport or catalysis. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: InterPro:IPR002048 SUPPORTS TRANSFER Exact target InterPro cross-reference is present; the domain mapping is assessed with independent functional evidence and does not establish all-product equivalence. |
| GO:0005515 protein binding | IPI PMID:11375975 The hemidesmosomal protein bullous pemphigoid antigen 1 and ... | KEEP AS NON CORE | Summary: ERBIN association is positive but does not establish a more specific DST activity. Reason: PMID:11375975 tests human BPAG1 N-terminal fragments against ERBIN fragments in yeast and a GST pull-down from transfected-cell lysate. ERBIN sequences upstream of its PDZ domain mediate this interaction, so PDZ-domain binding is not an appropriate refinement. The paper does not establish ERBIN as a constitutive hemidesmosomal component or a DST signaling activity. Retain the supported association under the CLINGEN project policy. |
| GO:0005515 protein binding | IPI PMID:12482924 Analysis of the interactions between BP180, BP230, plectin a... | MODIFY | Summary: The positive COL17A1 association supports collagen binding with an intracellular interface. Reason: The PMID:12482924 abstract and independently read PMID:10637308 support BP230 binding to the cytoplasmic region of type XVII collagen/BP180. GO:0005518 describes binding to collagen and does not require an extracellular triple-helical interface. The refinement therefore identifies the partner class while explicitly retaining the intracellular fragment scope; it does not assert binding to processed extracellular collagen or all DST products. The full PMID:12482924 original was not recovered. Proposed replacements: collagen binding |
| GO:0005515 protein binding | IPI PMID:17043677 Disrupted in Schizophrenia 1 Interactome: evidence for the c... | KEEP AS NON CORE | Summary: The DISC1 screen reports a positive association without a resolved narrower binding class. Reason: Literal PMID:17043677 records retain human DISC1 and DST identities and yeast two-hybrid fragment scope. DISC1 is a multifunctional neuronal organizer; its effects on microtubule networks alone do not establish that the tested partner is a structural cytoskeletal component for a GO:0008092 refinement. The original full text is unavailable here. Retain the positive interaction, with independent PMID:31413325 screen evidence, without transferring DISC1 developmental functions to DST. |
| GO:0005515 protein binding | IPI PMID:19632184 An EB1-binding motif acts as a microtubule tip localization ... | MODIFY | Summary: The EB1 interaction is binding to a cytoskeletal protein. Reason: PMID:19632184 curated records identify EB1/MAPRE1 and a DST C-terminal peptide. The deposited 3GJO entity retains a historical accession label, but its actual 30-residue sequence exactly matches Q03001-7 residues 7541–7570 and the corresponding tails of Q03001-8 and -14. Thus no paralog-misattribution claim is warranted. Primary structure and independent PMID:22995871 tail experiments support GO:0008092; this is not evidence for a complete natural-product assay. Proposed replacements: cytoskeletal protein binding |
| GO:0005515 protein binding | IPI PMID:19932097 BPAG1 isoform-b: complex distribution pattern in striated an... | MODIFY | Summary: Plectin is an independently established cytoskeletal binding partner. Reason: The authentic PMID:19932097 abstract positively reports direct binding of the BPAG1b N-terminal region to plectin and alpha-actinin and their complexes. Official plectin annotation establishes a cytoskeletal linker, making GO:0008092 a warranted partner-class refinement. Exact full-paper construct sequences and species for each assay remain unverified; the refinement does not imply all nine human products or a purified full-length pair. Proposed replacements: cytoskeletal protein binding |
| GO:0005515 protein binding | IPI PMID:21911577 A physical interaction network of dengue virus and human pro... | MODIFY | Summary: Sequence-checked fragment interactions identify dengue NS5 as the RNA-polymerase partner. Reason: The literal P29991-PRO_0000037946 identifier maps to dengue NS5. PMID:21911577 uses a human liver library and sequence-checked viral fragments, followed by quadruplicate pairwise yeast retesting with independent ADE2/HIS3 selection and exclusion of promiscuous activators. Four curated records list NS5 sufficient-binding-region features 70–130, 56–267, 1–368 and 1–835. These features and the DST reference-sequence checksum do not authenticate complete experimental clones or a current natural DST product. The independently recovered original supports the screen controls; no DST-specific split-luciferase validation is asserted. GO:0070063 identifies the verified RNA-polymerase partner class without requiring a catalytic-domain interface. It implies neither DST polymerase activity nor host-polymerase binding, native infection participation or full-length DST binding. Proposed replacements: RNA polymerase binding |
| GO:0005515 protein binding | IPI PMID:22995871 Calcium tips the balance: a microtubule plus end to lattice ... | MODIFY | Summary: The reported EB1 association supports cytoskeletal protein binding. Reason: PMID:22995871 directly studies the BP4 C-terminal tail and its EB1-binding region, with calcium and EF-hand perturbations. Preserve the literal mouse Q61166 partner and the unresolved exact origin/coordinates of the historical BP4 constructs; a human host is not construct identity. EB1 is a microtubule-associated cytoskeletal protein. The binding-class refinement does not require a native pathway claim or all-product equivalence. Proposed replacements: cytoskeletal protein binding |
| GO:0005515 protein binding | IPI PMID:23414517 A human skeletal muscle interactome centered on proteins inv... | KEEP AS NON CORE | Summary: APPL1 association is supported in a muscle interaction context. Reason: PMID:23414517 curated records include two human fragment yeast-two-hybrid interactions with favorable PBS classification and a proximity-ligation observation in human muscle. Proximity ligation is not a purified binary interface. APPL1 is a multifunctional endosomal/signaling adaptor; binding to it does not give DST adaptor activity. No narrower binding class has been established from these assays, so retain this positive association as non-core. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: Human EB1 co-complex recovery supports cytoskeletal protein binding. Reason: The exact PMID:26496610 interaction record identifies human MAPRE1 and DST in an anti-tag coimmunoprecipitation assay in HeLa cells. EB1 has an independently established microtubule cytoskeletal role, supporting GO:0008092 without claiming purified direct contact. Direct DST-tail/EB1 evidence from PMID:19632184 and PMID:22995871 corroborates the gene-level interaction while preserving this record’s own assay scope. Proposed replacements: cytoskeletal protein binding |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: The mouse EB1 pair supports the same cytoskeletal partner class. Reason: The exact PMID:26496610 record identifies mouse Q61166 with human DST in a HeLa coimmunoprecipitation context. The host does not change partner species. Independent EB1 structural function supports GO:0008092, and the direct tail evidence corroborates the general interaction without upgrading this co-complex assay to a purified binary test. Proposed replacements: cytoskeletal protein binding |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: BioPlex EB1-associated recovery supports the cytoskeletal binding class. Reason: The PMID:28514442 record reports MAPRE1/DST in the HEK293T affinity-purification mass-spectrometry workflow using tagged human ORFs. This is co-complex recovery, not proof of a direct interface. The independently established EB1 cytoskeletal role warrants GO:0008092; independent tail experiments support the interaction without changing the primary screen’s scope. Proposed replacements: cytoskeletal protein binding |
| GO:0005515 protein binding | IPI PMID:31413325 HENA, heterogeneous network-based data set for Alzheimer's d... | KEEP AS NON CORE | Summary: The human-brain screen independently supports DISC1 association. Reason: PMID:31413325 reports a newly performed, controlled human-brain-library yeast screen, and its exact DST–DISC1 record includes a DST fragment pool spanning 3157–5009. Retain the positive association with the same confidence convention as other screened pairs. A more specific DST activity or cytoskeletal binding class is not established simply by DISC1’s regulatory effects on neuronal organization. No Alzheimer-disease or neuronal-development function is inferred from the pair alone. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Repeated EB1-associated recovery supports cytoskeletal protein binding. Reason: PMID:33961781 exact records report the MAPRE1/DST pair in 293T and HCT116 affinity-purification mass-spectrometry contexts. Separately recovered original Methods establish tagged human ORF and lysate-complex capture scope. GO:0008092 follows from EB1’s verified cytoskeletal class; neither the two hosts nor co-purification proves a purified direct interface or every DST product. Proposed replacements: cytoskeletal protein binding |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: OpenCell endogenous MAPRE1-associated DST recovery supports the cytoskeletal partner class. Reason: PMID:35271311 uses endogenous tagging and affinity-purification mass spectrometry in HEK293T cells. The raw public CSV contains two MAPRE1-bait DST prey groups; their complete accession groups are preserved and cannot be assigned to one natural isoform. Together with EB1’s established cytoskeletal role and independent tail-binding experiments this supports GO:0008092, while this source remains a co-complex assay. Proposed replacements: cytoskeletal protein binding |
| GO:0005604 basement membrane | TAS PMID:2461961 Isolation of complementary DNA for bullous pemphigoid antige... | MODIFY | Summary: The extracellular basement-membrane term should be refined to the intracellular hemidesmosomal plaque. Reason: PMID:2461961 uses historical basement-membrane-zone autoantibody terminology for the 230-kDa antigen. Later human BP230 fragment/localization studies establish an intracellular hemidesmosomal cytolinker, whereas GO:0005604 is an extracellular matrix structure. Refinement to GO:0030056 preserves the positive junctional localization and does not allege that the old immunofluorescence signal was false. This is a TAS assertion; the scanned original body was not independently recovered. Proposed replacements: hemidesmosome |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | KEEP AS NON CORE | Summary: DST was detected in a purified human sperm-nuclear preparation. Reason: The author thesis explicitly links Annex 8.2 to PMID:21630459. Its target table lists Q03001/BPAG1 with 1.4% coverage and three peptides; the actual table page was visually inspected. Methods use human semen, detergent/DTT tail separation, digitonin washes and nuclear-purity assessment. This supports contextual nuclear detection without assigning a specific product, nuclear mechanism, or universal localization. The normal publication cache remains abstract-only. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The nuclear annotation has positive contextual support. Reason: Official subcellular annotation is independently supported by the target-resolved human sperm-nucleus proteomic table and the mouse/construct-localization evidence summarized in PMID:14576348. Retain nucleus as a non-core pool; low-coverage proteomic detection and historical fusion experiments do not establish a nuclear function or all-product localization. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0191 SUPPORTS TRANSFER Source mapping is retained; independent target or donor evidence and its scope are explained in the row rationale. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse Dst provides a genuine nuclear-localization donor. Reason: UniProt Q91ZU6 is mouse Dst, not MACF1. Its current IDA donor annotation cites PMID:14576348, whose authentic abstract reports antibody-defined nuclear pools and N-terminal fusion/NLS experiments in C2C12 myoblasts. Human sperm-nuclear detection independently supports the gene-level location. Retain the ISS assertion with product and organism limits, without a donor-error allegation. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q91ZU6 SUPPORTS TRANSFER Authenticated mouse Dst/Q91ZU6 donor; original organism and historical product/construct scope are retained. No wrong-paralog or donor-count objection. |
| GO:0005635 nuclear envelope | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear-envelope association is a contextual neuronal pool. Reason: The curated location is supported by the authentic PMID:18638474 abstract: mouse sensory-neuron dystonin associates with ER and nuclear envelope, and an N-terminal dystonin-a2 fusion interacts with nesprin-3alpha. The full original is unavailable, so exact fusion sequence and mapping to a current human product are unresolved. Retain the positive non-core location without assigning a nuclear-envelope structural mechanism to all products. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0178 SUPPORTS TRANSFER Source mapping is retained; independent target or donor evidence and its scope are explained in the row rationale. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Cytoplasmic localization is a valid broad location across multiple products. Reason: The exact PTN002753757 IBD and target lineage are recovered. Independent epithelial and tail experiments establish cytoplasmic pools, but the gene also has positive nuclear and membrane-associated contexts. Retain this broad positive location as non-core rather than replace it with a single compartment that would lose valid pools. Self-inclusion in the IBD descendant evidence is expected and is not circularity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002753757 SUPPORTS TRANSFER Literal IBD, aligned target sequence and complete target-to-root path authenticated in PTHR23169; the node is ancestral to human DST. No target-specific loss or misplaced-node evidence was found; contextual scope is retained where appropriate. |
| GO:0005737 cytoplasm | IDA PMID:11751855 Novel alternative splicings of BPAG1 (bullous pemphigoid ant... | KEEP AS NON CORE | Summary: Retain the experimentally curated cytoplasmic location. Reason: PMID:11751855 is abstract-only after bounded primary-access attempts, so its exact microscopy panel is not claimed read. Independent human epithelial BP230 studies and cytoplasmic tail experiments establish the general location. Retain the IDA assertion with this access limit and product scope rather than negate it from an incomplete cache. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The ER membrane is a supported neuronal/product-dependent pool. Reason: The official electronic mapping is biologically consistent with PMID:18638474, whose authentic abstract describes endogenous mouse sensory-neuron ER association and an N-terminal transmembrane dystonin-a2 fusion. Preserve the positive location and historical construct boundary. This is not evidence that every human product is an integral ER membrane protein or that the ER pool performs all cytoskeletal functions. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0097 SUPPORTS TRANSFER Source mapping is retained; independent target or donor evidence and its scope are explained in the row rationale. |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The mouse Dst ER-membrane donor is coherent with a conserved contextual pool. Reason: The literal Q91ZU6 donor is mouse Dst. Its curated ER/NE localization and the authentic PMID:18638474 abstract support the source, including a transmembrane N-terminal fusion and endogenous sensory-neuron observations. The full Methods and exact human product equivalence are unresolved, but no target-specific loss or contradictory biology was found. Retain the ISS location as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q91ZU6 SUPPORTS TRANSFER Authenticated mouse Dst/Q91ZU6 donor; original organism and historical product/construct scope are retained. No wrong-paralog or donor-count objection. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2213192 | KEEP AS NON CORE | Summary: Reactome models a cytosolic BPAG1e-containing assembly intermediate. Reason: The actual R-HSA-2213192 event has an input BPAG1e:Plectin complex R-HSA-2220789 in cytosol. This is a target-resolved modeled pool in hemidesmosome formation, not an inference from the overall pathway compartment. Retain the contextual cytosol annotation without treating it as exhaustive or as an independently measured diffuse soluble pool. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000120 | MODIFY | Summary: The cytoskeletal location can be resolved into the three supported networks. Reason: Human epithelial BP230 supports intermediate-filament anchorage, while product-specific long neural/muscle and tail evidence supports actin and microtubule networks. Replace the broad InterPro/subcellular mapping with the supported intermediate-filament, actin and microtubule cytoskeleton terms. This is a gene-level synthesis across products, not evidence that every product simultaneously occupies all three networks. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR001101 SUPPORTS TRANSFER Exact target InterPro cross-reference is present; the domain mapping is assessed with independent functional evidence and does not establish all-product equivalence. UniProtKB-SubCell:SL-0090 SUPPORTS TRANSFER Source mapping is retained; independent target or donor evidence and its scope are explained in the row rationale. Proposed replacements: intermediate filament cytoskeleton actin cytoskeleton microtubule cytoskeleton |
| GO:0005882 intermediate filament | IBA GO_REF:0000033 | ACCEPT | Summary: The conserved intermediate-filament association is central to DST biology. Reason: The literal PTN002753757 IBD is ancestral to human DST and is grounded in plakin-family cytoskeletal evidence. Human epithelial BP230 interactions independently support intermediate-filament anchorage. Preserve the source annotation and its original metadata without converting association with the filament system into a claim that DST is the filament polymer. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002753757 SUPPORTS TRANSFER Literal IBD, aligned target sequence and complete target-to-root path authenticated in PTHR23169; the node is ancestral to human DST. No target-specific loss or misplaced-node evidence was found; contextual scope is retained where appropriate. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: DST associates with the cytoplasmic face of the plasma membrane. Reason: Human epithelial BP230 binding to membrane-spanning integrin beta4 and collagen XVII, plus basal and leading-edge localization in PMID:19403692, supports the positive plasma-membrane location. It is peripheral/product-dependent rather than evidence of a universal transmembrane DST architecture. Retain the broad location as non-core alongside the separately supported functional subcompartments. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0039 SUPPORTS TRANSFER Source mapping is retained; independent target or donor evidence and its scope are explained in the row rationale. |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | KEEP AS NON CORE | Summary: The focal-adhesion proteomic context is plausible and retained with target-table limits. Reason: PMID:21423176 Methods describe isolated human fibroblast focal adhesions with residual fragmented stress fibers and reproducible LC-MS sampling. The target-specific supplemental row was not recovered; the available supplementary ZIP did not contain that table. Independent mouse Dst IDA focal-adhesion annotation and the accepted IBA support the location. Retain this HDA observation as contextual, without inventing target measurements or treating preparation admixture as proof of contamination. |
| GO:0005925 focal adhesion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The PAINT focal-adhesion annotation has an authentic Dst donor lineage. Reason: The exact PTN002753862 IBD lies above the target leaf and uses MGI:104627, authenticated as mouse Dst/Q91ZU6. Its current IDA focal-adhesion assertion cites PMID:14576348. The original abstract verifies broader cytoskeletal/nuclear localization but not the exact focal-adhesion panel; this is an access limit, not a donor error. Retain the conserved contextual pool. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002753862 SUPPORTS TRANSFER Literal IBD, aligned target sequence and complete target-to-root path authenticated in PTHR23169; the node is ancestral to human DST. No target-specific loss or misplaced-node evidence was found; contextual scope is retained where appropriate. |
| GO:0005938 cell cortex | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cell-cortex association is a valid contextual subcellular location. Reason: The official subcellular mapping agrees with human basal/leading-front epithelial BP230 and junctional interactions. These positive observations support cortical association without identifying a uniform cortical distribution in every cell or all products. Retain the broad location as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0138 SUPPORTS TRANSFER Source mapping is retained; independent target or donor evidence and its scope are explained in the row rationale. |
| GO:0007010 cytoskeleton organization | IMP PMID:19403692 BPAG1e maintains keratinocyte polarity through beta4 integri... | MODIFY | Summary: The perturbation resolves actin-cytoskeleton organization specifically. Reason: PMID:19403692 uses BPAG1e depletion in human keratinocytes and measures actin lamellipodial organization, focal-adhesion pattern and polarity, while reporting no obvious gross microtubule or keratin-network difference in that assay. GO:0030036 therefore captures the demonstrated actin organization role more precisely than generic cytoskeleton organization. This does not negate other DST products’ microtubule/intermediate-filament functions. Proposed replacements: actin cytoskeleton organization |
| GO:0007229 integrin-mediated signaling pathway | NAS PMID:11375975 The hemidesmosomal protein bullous pemphigoid antigen 1 and ... | KEEP AS NON CORE | Summary: Integrin-coupled signaling is supported as an epithelial context. Reason: PMID:11375975 establishes BP230 association with beta4 and ERBIN but presents some assembly/signaling roles as hypotheses. Independent PMID:19403692 directly links BPAG1e depletion to reduced beta4-associated Rac1, reduced Rac1 activity and altered cofilin/polarity. Retain integrin-mediated signaling as a contextual role without assigning DST intrinsic GEF or kinase activity or assuming direct Rac1 binding. |
| GO:0008017 microtubule binding | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved microtubule binding is a core property of relevant long DST products. Reason: The exact PTN002753862 IBD and human target path are authenticated. Mouse Dst IDA PMID:10428034 and human target descendants provide legitimate grounding, while PMID:22995871 directly tests microtubule-binding tail behavior. Self-inclusion is not circular and a short donor list does not weaken the ancestral assertion. The claim is gene-level, not shared by all nine products. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002753862 SUPPORTS TRANSFER Literal IBD, aligned target sequence and complete target-to-root path authenticated in PTHR23169; the node is ancestral to human DST. No target-specific loss or misplaced-node evidence was found; contextual scope is retained where appropriate. |
| GO:0008017 microtubule binding | IEA GO_REF:0000120 | ACCEPT | Summary: Domain-based microtubule binding agrees with direct functional evidence. Reason: The InterPro microtubule-associated domain mappings and retrieved ARBA rule are consistent with PMID:22995871 tail experiments and conserved Dst binding summarized in PMID:10428034. Unresolved detailed FunFam condition membership is recorded separately; it does not overturn the independently supported activity. Calcium-dependent localization switching is distinct from a quantitatively proven increase in purified microtubule affinity. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00043642 UNRESOLVED Actual rule and target domains/lineage were retrieved. Precise membership in all FunFam conditions was not independently resolved; biological disposition rests additionally on the cited primary/curated evidence, not an invented rule failure. InterPro:IPR003108 SUPPORTS TRANSFER Exact target InterPro cross-reference is present; the domain mapping is assessed with independent functional evidence and does not establish all-product equivalence. InterPro:IPR036534 SUPPORTS TRANSFER Exact target InterPro cross-reference is present; the domain mapping is assessed with independent functional evidence and does not establish all-product equivalence. |
| GO:0008090 retrograde axonal transport | ISS GO_REF:0000024 | ACCEPT | Summary: DST participates in retrograde axonal transport as a linker/adaptor. Reason: The literal mouse Dst donor and PMID:14581450 support ERM-region association with dynactin and disrupted retrograde transport in mouse neurons, including dominant-negative and knockout experiments. Dynein provides force; DST is not assigned autonomous motor catalysis. The historical long neural n4 construct is not silently mapped to the short current human neural aliases. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q91ZU6 SUPPORTS TRANSFER Authenticated mouse Dst/Q91ZU6 donor; original organism and historical product/construct scope are retained. No wrong-paralog or donor-count objection. |
| GO:0009611 response to wounding | IDA PMID:19403692 BPAG1e maintains keratinocyte polarity through beta4 integri... | KEEP AS NON CORE | Summary: The wound response is a contextual polarized-migration role. Reason: PMID:19403692 measures BPAG1e localization and directional migration after scratch wounding, with perturbation and Rac1/cofilin rescue. This supports more than a simple abundance-response inference. Retain response to wounding as non-core alongside the more mechanistically informative polarity/actin/migration annotations; migration speed itself was not significantly changed. |
| GO:0009925 basal plasma membrane | NAS PMID:11375975 The hemidesmosomal protein bullous pemphigoid antigen 1 and ... | ACCEPT | Summary: Basal plasma-membrane association is central to epithelial hemidesmosomal anchorage. Reason: PMID:11375975 establishes epithelial BP230 partnerships with beta4 and BP180, and independent PMID:19403692 places BPAG1e at the basal surface of stationary human keratinocytes. Retain this product-specific functional location without claiming all natural products reside at the basal membrane. |
| GO:0015629 actin cytoskeleton | IEA GO_REF:0000117 | ACCEPT | Summary: Relevant DST products associate with the actin cytoskeleton. Reason: The retrieved ARBA rule contains a condition set matching the target CH/EF-hand InterPro annotations and Haplorrhini lineage. PMID:14576348 independently reports antibody/fusion stress-fiber localization, while human keratinocyte perturbation in PMID:19403692 supports actin-system function. This gene-level annotation does not override any product-specific absence of an actin-binding domain. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00029230 SUPPORTS TRANSFER Actual rule and target domains/lineage were retrieved. A condition set matches the explicit InterPro and lineage data. |
| GO:0015630 microtubule cytoskeleton | IEA GO_REF:0000117 | ACCEPT | Summary: The microtubule cytoskeleton is a central location of relevant long DST products. Reason: The electronic annotation is independently supported by the tail localization/binding experiments in PMID:22995871 and conserved neuronal evidence in PMID:10428034. The retained long products contain the relevant C-terminal architecture; short aliases and engineered tails are not treated as equivalent full-length proteins. The rule was retrieved without inventing unresolved FunFam membership. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00029268 UNRESOLVED Actual rule and target domains/lineage were retrieved. Precise membership in all FunFam conditions was not independently resolved; biological disposition rests additionally on the cited primary/curated evidence, not an invented rule failure. |
| GO:0016020 membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The ancestral broad membrane association remains valid. Reason: The literal PTN002753757 IBD is above human DST and is supported by family membrane-associated cytolinkers. Independent human epithelial and mouse neuronal ER/NE evidence establishes multiple distinct membrane pools. Retain the broad association as non-core rather than choose one narrower compartment that would exclude another positive context. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002753757 SUPPORTS TRANSFER Literal IBD, aligned target sequence and complete target-to-root path authenticated in PTHR23169; the node is ancestral to human DST. No target-specific loss or misplaced-node evidence was found; contextual scope is retained where appropriate. |
| GO:0016020 membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The electronic membrane mapping is consistent with several positive membrane-associated pools. Reason: Human BP230 associates with basal/leading-edge plasma membrane structures, and mouse sensory-neuron Dst has ER/NE association. This broad positive location is retained as non-core. It is not evidence that all DST products cross a membrane, nor is one specific membrane an exhaustive replacement. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0162 SUPPORTS TRANSFER Source mapping is retained; independent target or donor evidence and its scope are explained in the row rationale. |
| GO:0030011 maintenance of cell polarity | IMP PMID:19403692 BPAG1e maintains keratinocyte polarity through beta4 integri... | ACCEPT | Summary: BPAG1e directly contributes to front–rear polarity in human keratinocytes. Reason: PMID:19403692 uses independent knockdown clones and measures lost front–rear polarization and directional persistence. Active Rac1/cofilin rescues support a mechanism linking beta4-associated cytoskeleton to polarity. Retain the process as core in the epithelial product context, without assigning direct nucleotide-exchange activity or a universal migration effect. Supporting Evidence: |
| GO:0030018 Z disc | IEA GO_REF:0000120 | ACCEPT | Summary: The muscle BPAG1b pool has positive Z-disc localization. Reason: The authentic PMID:19932097 abstract reports ultrastructural Z-disc localization and colocalization with alpha-actinin, plectin and desmin, together with N-terminal interaction evidence. This supports the curated gene-level muscle location. The full original and complete construct sequences were not recovered; do not transfer the Z-disc pool to every natural product or claim all experiments were human. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00086242 UNRESOLVED Actual rule and target domains/lineage were retrieved. Precise membership in all FunFam conditions was not independently resolved; biological disposition rests additionally on the cited primary/curated evidence, not an invented rule failure. UniProtKB-SubCell:SL-0314 SUPPORTS TRANSFER Source mapping is retained; independent target or donor evidence and its scope are explained in the row rationale. |
| GO:0030056 hemidesmosome | IBA GO_REF:0000033 | ACCEPT | Summary: The hemidesmosomal location is conserved and directly corroborated in human cells. Reason: The exact PTN002753862 IBD is ancestral to human DST, with authentic mouse Dst and human target evidence. Human BP230 interaction and localization experiments independently establish the intracellular hemidesmosomal plaque role. Target self-grounding is legitimate and no lineage-specific loss was found. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002753862 SUPPORTS TRANSFER Literal IBD, aligned target sequence and complete target-to-root path authenticated in PTHR23169; the node is ancestral to human DST. No target-specific loss or misplaced-node evidence was found; contextual scope is retained where appropriate. |
| GO:0030056 hemidesmosome | IEA GO_REF:0000120 | ACCEPT | Summary: The electronic hemidesmosomal mapping is directly supported for epithelial BP230. Reason: Human epithelial BP230 interaction studies establish integrin beta4/collagen XVII contacts and the basal plaque architecture. The retrieved rule/subcellular mapping agrees with this biology; unresolved detailed rule-condition membership is not substituted for the independent experimental support. This is not a location shared by all natural DST products. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00086288 UNRESOLVED Actual rule and target domains/lineage were retrieved. Precise membership in all FunFam conditions was not independently resolved; biological disposition rests additionally on the cited primary/curated evidence, not an invented rule failure. UniProtKB-SubCell:SL-0137 SUPPORTS TRANSFER Source mapping is retained; independent target or donor evidence and its scope are explained in the row rationale. |
| GO:0030056 hemidesmosome | TAS PMID:11375975 The hemidesmosomal protein bullous pemphigoid antigen 1 and ... | ACCEPT | Summary: Human BP230 is a hemidesmosomal cytolinker. Reason: PMID:11375975 directly studies human BPAG1 interactions with beta4, BP180 and ERBIN and discusses BP230 in the hemidesmosomal plaque. Retain the TAS location, supported independently by PMID:10637308. ERBIN’s separate interaction does not make ERBIN a structural component of that plaque. |
| GO:0030056 hemidesmosome | TAS PMID:8575775 Cloning and characterization of the neural isoforms of human... | ACCEPT | Summary: Retain the established epithelial hemidesmosomal location. Reason: PMID:8575775 is retained as the historical TAS reference; its complete experimental body was not independently read. Direct human BP230 interaction/localization evidence from PMID:10637308 and PMID:11375975 independently establishes the gene-level hemidesmosomal location, so an incomplete older cache does not justify deletion or a contrary localization claim. |
| GO:0030424 axon | IEA GO_REF:0000120 | ACCEPT | Summary: Axonal localization is integral to the neuronal cytolinker/transport context. Reason: The official mapping agrees with PMID:14581450 native mouse nerve localization, ligature and neuronal transport observations, and with the conserved neuronal microtubule phenotype summarized in PMID:10428034. Retain the gene-level location with organism/product limits; this does not map the historical long neural protein to current short aliases. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028032 UNRESOLVED Actual rule and target domains/lineage were retrieved. Precise membership in all FunFam conditions was not independently resolved; biological disposition rests additionally on the cited primary/curated evidence, not an invented rule failure. UniProtKB-SubCell:SL-0279 SUPPORTS TRANSFER Source mapping is retained; independent target or donor evidence and its scope are explained in the row rationale. |
| GO:0031252 cell leading edge | IDA PMID:19403692 BPAG1e maintains keratinocyte polarity through beta4 integri... | ACCEPT | Summary: Human BPAG1e localizes to the leading edge during directed migration. Reason: PMID:19403692 directly observes BPAG1e/beta4 at the leading front of migrating human keratinocytes, with altered polarity after depletion. Retain this functional subcellular location without erasing the separate basal pool in stationary cells or extending it to all products. Supporting Evidence: |
| GO:0031252 cell leading edge | IEA GO_REF:0000117 | ACCEPT | Summary: The electronic leading-edge mapping is experimentally corroborated. Reason: The retrieved ARBA assertion agrees with the target-specific human keratinocyte observations in PMID:19403692. The original stimulus and epithelial context remain explicit; unresolved detailed rule conditions do not invalidate this independently grounded location. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028924 UNRESOLVED Actual rule and target domains/lineage were retrieved. Precise membership in all FunFam conditions was not independently resolved; biological disposition rests additionally on the cited primary/curated evidence, not an invented rule failure. |
| GO:0031410 cytoplasmic vesicle | IDA PMID:14581450 BPAG1n4 is essential for retrograde axonal transport in sens... | ACCEPT | Summary: Vesicle-associated BPAG1n4 is a positive native localization observation. Reason: PMID:14581450 reports mouse immunoelectron microscopy reporting most labeled particles on vesicle-like structures, together with transport/dynactin context. Retain the IDA vesicle location; it is not appropriate to dismiss it as a nonspecific cytoplasmic pool. Historical long n4 naming is compatible with Q03001-14 architecture but is not complete clone-sequence authentication. Supporting Evidence: |
| GO:0031673 H zone | IEA GO_REF:0000044 | UNDECIDED | Summary: The precise H-zone assignment remains unresolved. Reason: The official curated location and electronic mapping are preserved, but the independently available PMID:19932097 abstract establishes Z-disc localization rather than resolving the H-zone observation. The full original could not be recovered, and no exact target H-zone panel was verified. This is uncertainty about the narrower compartment, not evidence that the curated claim is false or that Z-disc localization excludes it. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB-SubCell:SL-0477 UNRESOLVED Official subcellular mapping is preserved, but the precise H-zone evidence cannot be resolved from the accessible source. |
| GO:0035371 microtubule plus-end | IDA PMID:19632184 An EB1-binding motif acts as a microtubule tip localization ... | ACCEPT | Summary: The microtubule-plus-end location is supported by EB1-linked tail behavior. Reason: The exact PMID:19632184 full text was not recovered, but its curated target records and 3GJO sequence-resolved peptide evidence are retained. Independently read PMID:22995871 demonstrates BP4-tail plus-end localization and EB1-dependent behavior. Retain the experimental location with explicit fragment/construct scope, rather than overrule the curator from an incomplete cache. |
| GO:0042060 wound healing | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The conserved wound-healing context is retained without claiming a human organism-level rescue assay. Reason: The exact PTN002753757 IBD and descendant path are recovered. Donor evidence includes authentic Macf1/Eppk1 family wound-healing contexts; these are not mistaken for Dst experiments. Human BPAG1e contributes to polarized scratch-wound migration in PMID:19403692, coherently supporting the ancestral contextual role. Donor count and target self-evidence are not failure criteria. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002753757 SUPPORTS TRANSFER Literal IBD, aligned target sequence and complete target-to-root path authenticated in PTHR23169; the node is ancestral to human DST. No target-specific loss or misplaced-node evidence was found; contextual scope is retained where appropriate. |
| GO:0042803 protein homodimerization activity | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Self-dimerization is a curated structural property with unresolved assay/product boundaries. Reason: Official DST SUBUNIT annotation reports homodimerization and product-dependent N-terminal self-association. The retrieved ARBA rule agrees with that assertion. The exact PMID:19932097 self-association assay was not independently recoverable, so this is retained as a non-core assembly property with limited attribution, not generalized to all nine products or upgraded to an obligatory physiological oligomer. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00027933 UNRESOLVED Actual rule and target domains/lineage were retrieved. Precise membership in all FunFam conditions was not independently resolved; biological disposition rests additionally on the cited primary/curated evidence, not an invented rule failure. |
| GO:0045104 intermediate filament cytoskeleton organization | IBA GO_REF:0000033 | ACCEPT | Summary: Intermediate-filament organization is a conserved central cytolinker role. Reason: The exact PTN002753757 IBD lies above the human target and integrates authentic plakin-family structural evidence. Human epithelial BP230 interactions independently place DST in the physical linkage between hemidesmosomal transmembrane proteins and intermediate filaments. This supports participation through structure, not merely necessity, and does not require all products to bind intermediate filaments. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002753757 SUPPORTS TRANSFER Literal IBD, aligned target sequence and complete target-to-root path authenticated in PTHR23169; the node is ancestral to human DST. No target-specific loss or misplaced-node evidence was found; contextual scope is retained where appropriate. |
| GO:0045104 intermediate filament cytoskeleton organization | IEA GO_REF:0000002 | ACCEPT | Summary: The plakin-domain electronic mapping agrees with intermediate-filament organization. Reason: The InterPro mapping is supported by direct human epithelial BP230 junctional interactions and its established cytolinker architecture. Retain this structural participation while keeping product-specific domains distinct; a domain match alone is not used to assign neuronal motor catalysis or every natural product the same partners. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR043197 SUPPORTS TRANSFER Exact target InterPro cross-reference is present; the domain mapping is assessed with independent functional evidence and does not establish all-product equivalence. |
| GO:0045104 intermediate filament cytoskeleton organization | IEP PMID:11751855 Novel alternative splicings of BPAG1 (bullous pemphigoid ant... | ACCEPT | Summary: Retain the experimentally curated intermediate-filament organization role. Reason: PMID:11751855 is abstract-only here and describes diverse BPAG1 architectures. Its exact IEP experiment cannot be independently reconstructed. However, direct human epithelial BP230 studies independently establish the structural intermediate-filament linkage, so the gene-level process is sound and curator deference is appropriate rather than treating the missing full text as contradiction. |
| GO:0045104 intermediate filament cytoskeleton organization | NAS PMID:11375975 The hemidesmosomal protein bullous pemphigoid antigen 1 and ... | ACCEPT | Summary: Human BP230 contributes structure to the intermediate-filament anchoring system. Reason: PMID:11375975 and independently read PMID:10637308 establish interactions that integrate epithelial BP230 with hemidesmosomal membrane proteins. This is structural participation in intermediate-filament organization, not simply a downstream phenotype. Retain the NAS process in the epithelial-product context. |
| GO:0045111 intermediate filament cytoskeleton | IEA GO_REF:0000117 | ACCEPT | Summary: The intermediate-filament cytoskeleton is a core location of the epithelial cytolinker. Reason: The electronic rule agrees with the physical BP230 hemidesmosomal/intermediate-filament linkage established in human epithelial studies. The claim is gene-level and product-dependent; it does not imply that the protein itself polymerizes as an intermediate-filament subunit. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028480 UNRESOLVED Actual rule and target domains/lineage were retrieved. Precise membership in all FunFam conditions was not independently resolved; biological disposition rests additionally on the cited primary/curated evidence, not an invented rule failure. |
| GO:0048870 cell motility | IMP PMID:19403692 BPAG1e maintains keratinocyte polarity through beta4 integri... | MODIFY | Summary: BPAG1e supports persistent migration of human keratinocytes without measurably increasing their average speed. Reason: PMID:19403692 measures BPAG1e depletion in human E6/E7-immortalized epidermal keratinocytes. Single-cell trajectories show reduced processivity and excessive turning, while average speed is not significantly changed; Rac1/cofilin interventions restore the impaired behavior. GO:0051546 keratinocyte migration is a current descendant of cell migration and the original cell motility term, and captures the demonstrated cellular context. The refinement preserves positive IMP participation without assigning intrinsic exchange-factor activity or locomotor force to BPAG1e. Maintenance of cell polarity remains a distinct supported process. Proposed replacements: keratinocyte migration |
| GO:0051010 microtubule plus-end binding | IDA PMID:19632184 An EB1-binding motif acts as a microtubule tip localization ... | ACCEPT | Summary: Retain the curated plus-end-binding activity with its tail/EB1 scope. Reason: PMID:19632184 target evidence includes the sequence-resolved DST tail/EB1 structure and interaction records; the exact original body was not recovered. Independently read PMID:22995871 establishes an EB1-binding tail and microtubule-plus-end behavior. This coherently supports the curator’s positive activity without asserting that every natural product or an isolated full-length human protein was assayed. |
| GO:1904115 axon cytoplasm | IEA GO_REF:0000108 | ACCEPT | Summary: The axonal cytoplasm location follows a positively supported axonal transport role. Reason: The GO_REF:0000108 mapping derives from retrograde axonal transport, and PMID:14581450 independently shows neuronal axonal/vesicle-associated localization. Retain the location with native mouse and historical long-product limits; it is not evidence of a separate diffuse soluble pool or autonomous motor activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO:0008090 SUPPORTS TRANSFER Source mapping is retained; independent target or donor evidence and its scope are explained in the row rationale. |
| GO:0034452 dynactin binding | IPI PMID:14581450 BPAG1n4 is essential for retrograde axonal transport in sens... | NEW | Summary: The neuronal BPAG1n4 interaction region binds dynactin p150 and associates with native dynactin-containing complexes. Reason: PMID:14581450 maps BPAG1n4–p150 interactions using human brain-derived cDNA/library constructs and cellular coexpression. Native mouse nerve-tissue coimmunoprecipitations recover p150, p50 and dynein intermediate chain with BPAG1n4, supporting dynactin-complex association beyond inference from a subunit name. COS-7 and CHO are expression hosts; the native tissue and transport assays are mouse. The blot overlay uses lysate, not purified two-component reconstitution, and no exact current natural DST isoform is assigned. This partner-specific binding assertion is distinct from the existing EB1/plectin interactions and from the integrated GO:0008093 transport-adaptor activity, which is retained. It does not assign dynein motor catalysis to DST. Supporting Evidence: |
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Download this section (compressed HTML)Q: How do sequence-defined endogenous human DST products partition hemidesmosomal, microtubule, muscle and neuronal transport functions, especially where historical neural names overlap current short product records?
Q: What molecular arrangement connects epithelial BP230 and integrin beta4 to Rac1/cofilin-dependent polarity without assigning intrinsic exchange-factor activity to DST?
Q: Which product accounts for the curated H-zone location and the sperm-nuclear proteomic detection, and do these pools have functions distinct from cytoskeletal attachment?
Experiment: Use product-specific endogenous tags and sequence-resolved proteomics in human epithelial, muscle and neuronal models, coupled to rescue with authenticated full-length products, to separate natural-product function from historical fragment or alias assignments.
Experiment: Compare matched full-length and tail constructs under controlled calcium conditions for EB1 association, microtubule lattice/end binding and network behavior, measuring affinity separately from cellular localization.
Experiment: Test the neuronal dynactin-associated linker with selective interaction-site perturbations and cargo transport measurements while retaining dynein motor activity as a separate variable.
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