DIAPH1 is a diaphanous-related formin that couples Rho-family signaling to actin filament assembly. Its FH1–FH2 region promotes actin assembly, while an N-terminal regulatory region and C-terminal autoregulatory segment restrain activity until relieved by activated Rho proteins. Cytosolic and membrane-associated pools organize actin structures; additional nuclear, centrosomal and spindle-associated pools occur in specific cellular settings. DIAPH1 also participates in receptor-linked cytoskeletal signaling and PKD2 localization. Disruption of its regulation or expression affects platelet architecture, hearing and neurodevelopment. Alternative splicing produces three protein isoforms with differences in their internal sequences.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | KEEP AS NON CORE | Summary: Retain the experimentally detected RNA contact. Reason: DIAPH1 is explicitly present in the HeLa mRNA-interactome Table S1 (ENSG00000131504). UV crosslinking and stringent oligo(dT) capture support RNA contact, but the mass-spectrometry assignments were grouped by gene. This establishes neither a particular RNA substrate nor an isoform-specific regulatory mechanism. |
| GO:0003779 actin binding | IEA GO_REF:0000120 | ACCEPT | Summary: Retain actin binding as the molecular basis of the assembly function. Reason: The target has the annotated FH3 and GTPase-binding domains, and the inherited mouse activity is experimentally grounded. Human DIAPH1 fragments also assemble actin structures in platelet cytosol. The broad actin-binding term accommodates interactions with actin during assembly without restricting the claim to one polymerization state. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. ensembl:ENSMUSP00000111297 SUPPORTS TRANSFER The donor product is associated with mouse Diaph1 in the official UniProt cross-reference; it is not independent experimental evidence from O08808. InterPro:IPR010472 SUPPORTS TRANSFER The official InterPro entry, target domain match and current mapping were inspected. The domain-level mapping is assessed against whole-target experiments. InterPro:IPR010473 SUPPORTS TRANSFER The official InterPro entry, target domain match and current mapping were inspected. The domain-level mapping is assessed against whole-target experiments. Supporting Evidence: file:human/DIAPH1/DIAPH1-uniprot.txt file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005102 signaling receptor binding | NAS PMID:9360932 Nonsyndromic deafness DFNA1 associated with mutation of a hu... | KEEP AS NON CORE | Summary: Retain receptor binding with independent target evidence. Reason: The original 1997 report establishes human genetics and discusses Rho/formin biology; it does not directly assay a signaling-receptor interaction. Independent human RAGE–DIAPH1 experiments establish this activity. Retain the gene-level assertion with that explicit evidence distinction; DIAPH1 is an intracellular receptor partner, not a secreted receptor agonist. |
| GO:0005515 protein binding | IPI PMID:18218625 Biochemical characterization of the Rho GTPase-regulated act... | MODIFY | Summary: Specify RHOD binding as small GTPase binding. Reason: The original purified human-protein experiment explicitly reports weak mDia1 N-terminal binding to RhoD (Figure 6A). The positive interaction is real; actin-assembly rescue was established for RhoA/B/C, not RhoD. Small GTPase binding specifies the partner class without extending the functional assay. Proposed replacements: small GTPase binding |
| GO:0005515 protein binding | IPI PMID:18218625 Biochemical characterization of the Rho GTPase-regulated act... | MODIFY | Summary: Specify RHOC binding as small GTPase binding. Reason: Purified human mDia1 N-terminal fragments bind GTP-loaded RhoC; RhoC also relieves inhibition in the platelet-cytosol assembly assay. Small GTPase binding identifies the demonstrated partner class. The fragment assay does not establish identical behavior of all three current products. Proposed replacements: small GTPase binding |
| GO:0005515 protein binding | IPI PMID:18218625 Biochemical characterization of the Rho GTPase-regulated act... | MODIFY | Summary: Specify RHOA binding as small GTPase binding. Reason: Purified human mDia1 N-terminal fragments bind active RhoA, with nucleotide-dependent binding and relief of DID-mediated inhibition in the cytosol-based assembly assay. Small GTPase binding captures the direct partner class; no GTPase catalytic activity is assigned to DIAPH1. Proposed replacements: small GTPase binding |
| GO:0005515 protein binding | IPI PMID:18230650 Functional interactions between phosphatase POPX2 and mDia m... | MODIFY | Summary: Specify the POPX2/PPM1F interaction as protein phosphatase binding. Reason: The primary report includes co-immunoprecipitation and a bacterial-protein overlay using mDia1 residues 261–571 and POPX2. PPM1F is a protein phosphatase, so GO:0019903 supplies a supported partner class. Host-cell identity is not used to assign an unreported species or current isoform to every historical construct. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:18230650 POPX2 interacts with the formin protein mDia1 (DIAPH1). file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005515 protein binding | IPI PMID:18922799 Interaction of the RAGE cytoplasmic domain with diaphanous-1... | MODIFY | Summary: Specify binding to the signaling receptor RAGE. Reason: Human RAGE cytoplasmic-tail and human lung DIAPH1 constructs were tested by two-hybrid, pull-down and cellular co-immunoprecipitation. Mapping implicates the DIAPH1 FH1 region. This supports signaling receptor binding without assigning the receptor’s extracellular ligand-binding activity to DIAPH1; rat C6 signaling experiments are distinct from the human pair assays. Proposed replacements: signaling receptor binding Supporting Evidence: PMID:18922799 RAGE cytoplasmic domain interacts with Diaphanous-1 (Dia-1) both in vitro and in vivo. file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005515 protein binding | IPI PMID:22190034 Global landscape of HIV-human protein complexes. | KEEP AS NON CORE | Summary: Retain the engineered viral-bait association as non-core binding. Reason: The exact IntAct records EBI-6176962 and EBI-6178643 identify human DIAPH1 with HIV-1 retropepsin Q9Q2G4 in affinity-purification and pull-down assays. The viral bait carries a catalytic-site D25 mutation. These experiments support association but do not establish direct protease recognition, proteolytic regulation or a physiological wild-type infection mechanism. Retain the supported generic binding assertion as non-core under the explicit project policy; the protease-binding replacement is withdrawn. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Specify the BioPlex RHOD association as small GTPase binding. Reason: The exact BioPlex interaction record contains DIAPH1 and RHOD. The established partner class permits small GTPase binding. AP-MS supports association rather than direct contact or physiological stoichiometry; gene-level aggregation does not resolve the three products. The independent human fragment study supports the same pair, with weak binding specifically reported for RHOD. Proposed replacements: small GTPase binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Specify the BioPlex RHOC association as small GTPase binding. Reason: The exact BioPlex interaction record contains DIAPH1 and RHOC. The established partner class permits small GTPase binding. AP-MS supports association rather than direct contact or physiological stoichiometry; gene-level aggregation does not resolve the three products. The independent human fragment study demonstrates purified RHOC binding and relief of inhibition in the platelet-cytosol actin-assembly assay. Proposed replacements: small GTPase binding |
| GO:0005522 profilin binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain profilin binding as a regulatory interaction. Reason: The mouse donor has a direct profilin-binding annotation to PMID:9214622, whose abstract describes binding and coordinated membrane recruitment. Human DIAPH1 retains the proline-rich FH1 region. This conserved assembly-associated interaction is retained without claiming that the available donor abstract establishes each human product’s affinity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. ensembl:ENSMUSP00000111297 SUPPORTS TRANSFER The donor product is associated with mouse Diaph1 in the official UniProt cross-reference; it is not independent experimental evidence from O08808. Supporting Evidence: file:human/DIAPH1/DIAPH1-uniprot.txt file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005634 nucleus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain the inherited nuclear location. Reason: Mouse Diaph1 has a direct nuclear annotation to PMID:23558171, and the primary abstract reports nuclear formin-dependent actin assembly. The target UniProt record retains nuclear localization by similarity. This is a defensible contextual location; the available source does not establish constitutive nuclear localization or resolve human isoforms. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. ensembl:ENSMUSP00000111297 SUPPORTS TRANSFER The donor product is associated with mouse Diaph1 in the official UniProt cross-reference; it is not independent experimental evidence from O08808. UniProtKB-SubCell:SL-0191 SUPPORTS TRANSFER The subcellular-location mapping is assessed against the actual target UniProt entry and the source-specific evidence described above. Supporting Evidence: file:human/DIAPH1/DIAPH1-uniprot.txt file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the inherited nuclear location. Reason: Mouse Diaph1 has a direct nuclear annotation to PMID:23558171, and the primary abstract reports nuclear formin-dependent actin assembly. The target UniProt record retains nuclear localization by similarity. This is a defensible contextual location; the available source does not establish constitutive nuclear localization or resolve human isoforms. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. Supporting Evidence: file:human/DIAPH1/DIAPH1-uniprot.txt file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | MODIFY | Summary: Specify the demonstrated soluble cytoplasmic compartment. Reason: Cytoplasm is correct but broad. Human platelet-cytosol experiments and target-specific Reactome entities resolve the active soluble pool to cytosol. The replacement specifies this supported pool without denying additional membrane-associated, spindle or nuclear locations. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. ensembl:ENSMUSP00000111297 SUPPORTS TRANSFER The donor product is associated with mouse Diaph1 in the official UniProt cross-reference; it is not independent experimental evidence from O08808. UniProtKB-SubCell:SL-0086 SUPPORTS TRANSFER The subcellular-location mapping is assessed against the actual target UniProt entry and the source-specific evidence described above. Proposed replacements: cytosol Supporting Evidence: Reactome:R-HSA-5665989 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | MODIFY | Summary: Specify the demonstrated soluble cytoplasmic compartment. Reason: Cytoplasm is correct but broad. Human platelet-cytosol experiments and target-specific Reactome entities resolve the active soluble pool to cytosol. The replacement specifies this supported pool without denying additional membrane-associated, spindle or nuclear locations. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. Proposed replacements: cytosol Supporting Evidence: Reactome:R-HSA-5665989 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain centrosomal localization in dividing neural progenitors. Reason: The source UniProt location has direct human support: endogenous DIAPH1 and pericentrin colocalize in mitotic ReNcell CX neural progenitor cells in PMID:24781755. The experiment establishes localization, not a separate centrosomal catalytic activity or a human spindle-loss phenotype. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0048 SUPPORTS TRANSFER The subcellular-location mapping is assessed against the actual target UniProt entry and the source-specific evidence described above. Supporting Evidence: file:human/DIAPH1/DIAPH1-uniprot.txt file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005819 spindle | IEA GO_REF:0000044 | MODIFY | Summary: Specify the experimentally observed mitotic spindle. Reason: Human neural progenitor immunofluorescence identifies DIAPH1 at the mitotic spindle, and the PKD2 study independently supports spindle association. GO:0072686 is the specific mitotic child of spindle; no meiotic localization is inferred. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB-SubCell:SL-0251 SUPPORTS TRANSFER The subcellular-location mapping is assessed against the actual target UniProt entry and the source-specific evidence described above. Proposed replacements: mitotic spindle |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5665982 | ACCEPT | Summary: Retain the target-specific cytosolic location. Reason: R-HSA-5665982 contains a RHOA–DIAPH1 complex whose DIAPH1 component resolves to cytosolic entity 5665970. The terminal protein reference is O60610 with GO:0005829. This location agrees with the human actin-assembly assays; membership does not establish every reaction attributed to other participants. Supporting Evidence: Reactome:R-HSA-5665982 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5665989 | ACCEPT | Summary: Retain the target-specific cytosolic location. Reason: R-HSA-5665989 directly takes the cytosolic DIAPH1 dimer (5665967) as an input. The terminal protein reference is O60610 with GO:0005829. This location agrees with the human actin-assembly assays; membership does not establish every reaction attributed to other participants. Supporting Evidence: Reactome:R-HSA-5665989 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666070 | ACCEPT | Summary: Retain the target-specific cytosolic location. Reason: R-HSA-5666070 includes DIAPH1 in the DIAPH1/DIAPH3 set (5666066), resolving through its dimer to cytosolic protein 5665970. The terminal protein reference is O60610 with GO:0005829. This location agrees with the human actin-assembly assays; membership does not establish every reaction attributed to other participants. Supporting Evidence: Reactome:R-HSA-5666070 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6785648 | ACCEPT | Summary: Retain the target-specific cytosolic location. Reason: R-HSA-6785648 contains the DIAPH1-bearing RHOA complex, resolving through its dimer to cytosolic protein 5665970. The terminal protein reference is O60610 with GO:0005829. This location agrees with the human actin-assembly assays; membership does not establish every reaction attributed to other participants. Supporting Evidence: Reactome:R-HSA-6785648 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013009 | ACCEPT | Summary: Retain the target-specific cytosolic location. Reason: R-HSA-9013009 includes the DIAPH1 dimer as an explicit member of the RHOA-effector set. The terminal protein reference is O60610 with GO:0005829. This location agrees with the human actin-assembly assays; membership does not establish every reaction attributed to other participants. Supporting Evidence: Reactome:R-HSA-9013009 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013110 | ACCEPT | Summary: Retain the target-specific cytosolic location. Reason: R-HSA-9013110 includes the DIAPH1 dimer as an explicit member of the RHOC-effector set. The terminal protein reference is O60610 with GO:0005829. This location agrees with the human actin-assembly assays; membership does not establish every reaction attributed to other participants. Supporting Evidence: Reactome:R-HSA-9013110 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9690493 | ACCEPT | Summary: Retain the target-specific cytosolic location. Reason: R-HSA-9690493 includes cytosolic DIAPH1 protein 5665970 as an explicit member of the RHOB-effector set. The terminal protein reference is O60610 with GO:0005829. This location agrees with the human actin-assembly assays; membership does not establish every reaction attributed to other participants. Supporting Evidence: Reactome:R-HSA-9690493 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9693125 | ACCEPT | Summary: Retain the target-specific cytosolic location. Reason: R-HSA-9693125 includes the DIAPH1 dimer as an explicit member of the RHOF-effector set. The terminal protein reference is O60610 with GO:0005829. This location agrees with the human actin-assembly assays; membership does not establish every reaction attributed to other participants. Supporting Evidence: Reactome:R-HSA-9693125 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9693198 | ACCEPT | Summary: Retain the target-specific cytosolic location. Reason: R-HSA-9693198 includes the DIAPH1 dimer as an explicit member of the RHOD-effector set. The terminal protein reference is O60610 with GO:0005829. This location agrees with the human actin-assembly assays; membership does not establish every reaction attributed to other participants. Supporting Evidence: Reactome:R-HSA-9693198 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9857585 | ACCEPT | Summary: Retain the target-specific cytosolic location. Reason: R-HSA-9857585 produces the cytosolic DIAPH1 dimer; DIAPH1 is the expression output, not the transcriptional regulator. The terminal protein reference is O60610 with GO:0005829. This location agrees with the human actin-assembly assays; membership does not establish every reaction attributed to other participants. Supporting Evidence: Reactome:R-HSA-9857585 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | MODIFY | Summary: Specify the actin-filament component of the cytoskeleton. Reason: The generic cytoskeleton location can be resolved to actin filament on the integrated human assembly evidence and the verified ancestral cellular-component assertion. This refinement does not deny the independent microtubule and spindle contexts. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB-SubCell:SL-0090 SUPPORTS TRANSFER The subcellular-location mapping is assessed against the actual target UniProt entry and the source-specific evidence described above. Proposed replacements: actin filament |
| GO:0005884 actin filament | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the inherited actin-filament location. Reason: The human target PTN002509308 descends from the asserted PTN000575131 node. Its worm descendant EXC-6/Q9TYU9 has direct GO:0031941 filamentous-actin evidence to PMID:25771894, grounding the broader filament location. Human DIAPH1 assembly evidence is concordant. The ancestral assertion is assessed by tree placement, not donor count. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000575131 SUPPORTS TRANSFER The exact IBD and human descendant path are verified; experimental descendant and human evidence support the inherited assertion. The guide records the unresolved historical ZFIN identifier without treating donor count as a confidence measure. Supporting Evidence: GO_REF:0000033 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain peripheral plasma-membrane association. Reason: The target UniProt record and the mouse donor support membrane-associated formin pools. PMID:9214622 describes Rho/profilin/mDia recruitment at specialized plasma membranes, and target-specific Reactome DIAPH1 entities independently support the location. This is peripheral association, not a transmembrane topology claim. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0039 SUPPORTS TRANSFER The subcellular-location mapping is assessed against the actual target UniProt entry and the source-specific evidence described above. Supporting Evidence: file:human/DIAPH1/DIAPH1-uniprot.txt Reactome:R-HSA-6798743 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain peripheral plasma-membrane association. Reason: The target UniProt record and the mouse donor support membrane-associated formin pools. PMID:9214622 describes Rho/profilin/mDia recruitment at specialized plasma membranes, and target-specific Reactome DIAPH1 entities independently support the location. This is peripheral association, not a transmembrane topology claim. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. Supporting Evidence: file:human/DIAPH1/DIAPH1-uniprot.txt Reactome:R-HSA-6798743 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6798743 | KEEP AS NON CORE | Summary: Retain the explicitly modeled post-exocytosis membrane pool. Reason: The Reactome output set 6806534 contains DIAPH1 entity 6801557, whose reference is O60610 and compartment is plasma membrane. Retain this source-specific location; a granule-exocytosis event does not by itself make DIAPH1 an exocytosis enzyme or establish membrane-spanning topology. Supporting Evidence: Reactome:R-HSA-6798743 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6800426 | KEEP AS NON CORE | Summary: Retain the explicitly modeled post-exocytosis membrane pool. Reason: The Reactome output set 6806514 contains DIAPH1 entity 6801557, whose reference is O60610 and compartment is plasma membrane. Retain this source-specific location; a granule-exocytosis event does not by itself make DIAPH1 an exocytosis enzyme or establish membrane-spanning topology. Supporting Evidence: Reactome:R-HSA-6800426 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0005903 brush border | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain brush-border localization by experimentally grounded orthology. Reason: The mouse donor has an IDA brush-border annotation to PMID:22114352. The recovered original identifies mDia1 in isolated adult-mouse intestinal brush-border proteomics and describes brush-border isolation and mDia1 immunoblotting. This supports the inherited location, without asserting the paper’s proposed microvillus-tip mechanism or a human isoform-specific result. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. ensembl:ENSMUSP00000111297 SUPPORTS TRANSFER The donor product is associated with mouse Diaph1 in the official UniProt cross-reference; it is not independent experimental evidence from O08808. Supporting Evidence: PMID:22114352 the nucleator mDia1 has been identified in our proteomic analysis. file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0007010 cytoskeleton organization | IEA GO_REF:0000107 | MODIFY | Summary: Specify actin filament polymerization within cytoskeleton organization. Reason: DIAPH1 directly promotes actin assembly, supported by human fragment assays and cellular experiments. GO:0030041 is a supported descendant of this broad organizational process. Refine the existing assertion rather than add a duplicate; the independent microtubule-regulatory annotation remains intact. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. ensembl:ENSMUSP00000111297 SUPPORTS TRANSFER The donor product is associated with mouse Diaph1 in the official UniProt cross-reference; it is not independent experimental evidence from O08808. Proposed replacements: actin filament polymerization |
| GO:0007010 cytoskeleton organization | ISS GO_REF:0000024 | MODIFY | Summary: Specify actin filament polymerization within cytoskeleton organization. Reason: DIAPH1 directly promotes actin assembly, supported by human fragment assays and cellular experiments. GO:0030041 is a supported descendant of this broad organizational process. Refine the existing assertion rather than add a duplicate; the independent microtubule-regulatory annotation remains intact. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. Proposed replacements: actin filament polymerization |
| GO:0007420 brain development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain brain development as a contextual role. Reason: The mouse donor annotation derives from PMID:24781755. The original compares targeted mice with human loss-of-function cases and documents human fetal-brain expression and centrosomal localization. Mouse ventricular dilation coexists with preserved cortical organization and apical actin belts. Retain the developmental role without equating the human and mouse phenotypes or defining a new molecular core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. ensembl:ENSMUSP00000111297 SUPPORTS TRANSFER The donor product is associated with mouse Diaph1 in the official UniProt cross-reference; it is not independent experimental evidence from O08808. |
| GO:0007605 sensory perception of sound | TAS PMID:9360932 Nonsyndromic deafness DFNA1 associated with mutation of a hu... | KEEP AS NON CORE | Summary: Retain the hearing-related biological role. Reason: The original human pedigree study identifies a segregating DIAPH1 splice-donor alteration and cochlear expression. This supports the existing hearing-process statement, while its proposed hair-cell actin mechanisms remain hypotheses. The clinical role is contextual to the actin-assembly machinery. |
| GO:0030036 actin cytoskeleton organization | IEA GO_REF:0000002 | MODIFY | Summary: Specify actin filament polymerization within actin cytoskeleton organization. Reason: The mapped domain and mouse donor support the broader actin-organizational function. Human assembly experiments resolve the directly executed step to addition of actin into filaments. GO:0030041 is a descendant of GO:0030036; this is a refinement of an existing assertion, not a redundant new annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR010473 SUPPORTS TRANSFER The official InterPro entry, target domain match and current mapping were inspected. The domain-level mapping is assessed against whole-target experiments. Proposed replacements: actin filament polymerization |
| GO:0030036 actin cytoskeleton organization | ISS GO_REF:0000024 | MODIFY | Summary: Specify actin filament polymerization within actin cytoskeleton organization. Reason: The mapped domain and mouse donor support the broader actin-organizational function. Human assembly experiments resolve the directly executed step to addition of actin into filaments. GO:0030041 is a descendant of GO:0030036; this is a refinement of an existing assertion, not a redundant new annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. Proposed replacements: actin filament polymerization |
| GO:0030041 actin filament polymerization | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the ancestral actin-polymerization function. Reason: Human DIAPH1 is a descendant of PTN000575131. The raw IBD and actual tree are verified, with direct polymerization evidence on mouse Diaph1/O08808, Diaph2/O70566 and Diaph3/Q9Z207 descendants. One historical ZFIN seed was not resolved in the current tree; that bounded gap does not invalidate the experimentally grounded node or the concordant human assays. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000575131 SUPPORTS TRANSFER The exact IBD and human descendant path are verified; experimental descendant and human evidence support the inherited assertion. The guide records the unresolved historical ZFIN identifier without treating donor count as a confidence measure. |
| GO:0030041 actin filament polymerization | ISS GO_REF:0000024 | ACCEPT | Summary: Retain actin polymerization by sequence similarity. Reason: The mouse donor O08808 has direct actin-polymerization annotations, including PMID:23558171. Human DIAPH1 fragment and cellular experiments independently support the same assembly function. This is conserved functional transfer, not an inference from domain presence alone. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. Supporting Evidence: file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0030667 secretory granule membrane | TAS Reactome:R-HSA-6798743 | KEEP AS NON CORE | Summary: Retain the explicit secretory-granule membrane entity. Reason: The R-HSA-6798743 input set 6800420 includes DIAPH1 entity 6801368 with reference O60610 and compartment GO:0030667. This is a curated target-specific membrane-associated pool; the location is retained without transferring the exocytosis process or claiming an integral membrane protein. Supporting Evidence: Reactome:R-HSA-6798743 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0031175 neuron projection development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the inherited neurite-development role. Reason: The mouse donor has a direct annotation to PMID:18572016. The available primary abstract reports Dia1-dependent neurite outgrowth in Neuro2A cells and partial colocalization with neurochondrin in primary rat hippocampal neurons. These support a conserved contextual actin-related role, while exact construct species and human product scope are not resolved by the abstract. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. ensembl:ENSMUSP00000111297 SUPPORTS TRANSFER The donor product is associated with mouse Diaph1 in the official UniProt cross-reference; it is not independent experimental evidence from O08808. |
| GO:0031267 small GTPase binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain the conserved small-GTPase regulatory interaction. Reason: The target GTPase-binding domain matches IPR010473 at residues 84–268 and the mapping explicitly supplies this term. Mouse evidence and direct human Rho-binding experiments agree. This regulatory interaction controls the integrated actin-assembly unit rather than constituting another catalytic core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. ensembl:ENSMUSP00000111297 SUPPORTS TRANSFER The donor product is associated with mouse Diaph1 in the official UniProt cross-reference; it is not independent experimental evidence from O08808. InterPro:IPR010473 SUPPORTS TRANSFER The official InterPro entry, target domain match and current mapping were inspected. The domain-level mapping is assessed against whole-target experiments. Supporting Evidence: GO_REF:0000002 file:human/DIAPH1/DIAPH1-uniprot.txt file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0032587 ruffle membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain the membrane-ruffle location. Reason: The UniProt location and mouse donor have explicit experimental grounding in PMID:9214622, whose abstract describes mDia, profilin and RhoA at stimulated membrane ruffles. This supports a contextual membrane-associated actin pool; human isoform-specific targeting and constitutive residence are not established. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. ensembl:ENSMUSP00000111297 SUPPORTS TRANSFER The donor product is associated with mouse Diaph1 in the official UniProt cross-reference; it is not independent experimental evidence from O08808. UniProtKB-SubCell:SL-0301 SUPPORTS TRANSFER The subcellular-location mapping is assessed against the actual target UniProt entry and the source-specific evidence described above. Supporting Evidence: file:human/DIAPH1/DIAPH1-uniprot.txt file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0032886 regulation of microtubule-based process | IMP PMID:20937854 ErbB2 receptor controls microtubule capture by recruiting AC... | KEEP AS NON CORE | Summary: Retain regulation of microtubule behavior. Reason: In human SKBr3 cells, mDia1 knockdown reduces heregulin-induced inhibitory GSK3B phosphorylation within the MEMO1/RHOA pathway controlling peripheral microtubules. The original supports a regulatory role; it does not show that DIAPH1 itself phosphorylates GSK3B or performs APC/CLASP/ACF7 activities. |
| GO:0035372 protein localization to microtubule | IMP PMID:15123714 PKD2 interacts and co-localizes with mDia1 to mitotic spindl... | KEEP AS NON CORE | Summary: Retain the demonstrated PKD2-targeting role. Reason: Two DIAPH1 knockdown constructs remove PKD2 from human HeLa mitotic spindles while tubulin staining remains. This supports protein localization to microtubules in the tested context. |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain homomeric binding as an assembly property. Reason: The mouse donor has direct homomeric-binding annotations and the target is represented as a dimer in Reactome. DIAPH1 self-association is compatible with its formin assembly mechanism; this ancillary binding descriptor does not warrant a separate molecular core or imply equivalent behavior of every product. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. ensembl:ENSMUSP00000111297 SUPPORTS TRANSFER The donor product is associated with mouse Diaph1 in the official UniProt cross-reference; it is not independent experimental evidence from O08808. Supporting Evidence: file:human/DIAPH1/DIAPH1-uniprot.txt Reactome:R-HSA-5665989 file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0043005 neuron projection | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the inherited neuronal-process location. Reason: The mouse donor’s direct annotation cites PMID:18572016. Its abstract explicitly reports partial Dia1/neurochondrin colocalization in primary rat hippocampal neurons and neurite outgrowth in Neuro2A cells. Retain the contextual location without inventing a human neuronal isoform measurement. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. ensembl:ENSMUSP00000111297 SUPPORTS TRANSFER The donor product is associated with mouse Diaph1 in the official UniProt cross-reference; it is not independent experimental evidence from O08808. |
| GO:0044325 transmembrane transporter binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain transporter binding with independent target grounding. Reason: The mouse donor and human target have the same PKD2-binding evidence lineage. Human endogenous co-immunoprecipitation supports the class directly, so the orthology transfer is not an unsupported cycle. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. ensembl:ENSMUSP00000111297 SUPPORTS TRANSFER The donor product is associated with mouse Diaph1 in the official UniProt cross-reference; it is not independent experimental evidence from O08808. |
| GO:0044325 transmembrane transporter binding | IPI PMID:15123714 PKD2 interacts and co-localizes with mDia1 to mitotic spindl... | KEEP AS NON CORE | Summary: Retain binding to the PKD2 cation channel. Reason: Native human HEK293 co-immunoprecipitation supports the pair. PKD2 is a transmembrane cation transporter. The initial two-hybrid prey library was mouse; that distinction does not erase the independent human evidence. Supporting Evidence: PMID:15123714 mDia1 and PKD2 interact in native and in transfected cells file:human/DIAPH1/DIAPH1-evidence-guide.md |
| GO:0048488 synaptic vesicle endocytosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the inherited synaptic-vesicle retrieval role. Reason: The mouse donor has experimental synaptic-vesicle endocytosis annotations to PMID:28231467. Its primary abstract identifies mDia1-dependent actin assembly in membrane retrieval and endosome-like vacuole formation. Retain this conserved contextual process; the available access does not establish human isoform-specific kinetics or a direct clathrin interaction. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O08808 SUPPORTS TRANSFER Mouse Diaph1 identity and current experimental GO evidence were traced; the source-specific scope and human corroboration are described in the reason and guide. ensembl:ENSMUSP00000111297 SUPPORTS TRANSFER The donor product is associated with mouse Diaph1 in the official UniProt cross-reference; it is not independent experimental evidence from O08808. |
| GO:0051279 regulation of release of sequestered calcium ion into cytosol | IMP PMID:15123714 PKD2 interacts and co-localizes with mDia1 to mitotic spindl... | KEEP AS NON CORE | Summary: Retain the mitotic calcium-response phenotype. Reason: DIAPH1 knockdown reduces histamine-evoked intracellular calcium release in mitotic HeLa cells, including EGTA-buffered assays. The authors do not resolve whether the effect acts only through PKD2. |
| GO:0051493 regulation of cytoskeleton organization | IMP PMID:26912466 A gain-of-function variant in DIAPH1 causes dominant macroth... | KEEP AS NON CORE | Summary: Retain the experimentally supported cytoskeletal regulatory role. Reason: The original examines human platelets with DIAPH1 R1213* and compares wild-type and mutant constructs in human cell lines. F-actin and microtubule changes support the broad regulatory process, with independent DIAPH2/3 expression controls. Actin polymerization is the integrated core; the mutation phenotype is not an additional molecular function. |
| GO:0071420 cellular response to histamine | IMP PMID:15123714 PKD2 interacts and co-localizes with mDia1 to mitotic spindl... | KEEP AS NON CORE | Summary: Retain the cell-cycle-specific histamine response. Reason: The primary assays show reduced histamine-evoked calcium release after DIAPH1 knockdown in mitotic HeLa cells; the corresponding interphase response is unchanged. Retain that bounded context. |
| GO:0072686 mitotic spindle | IDA PMID:15123714 PKD2 interacts and co-localizes with mDia1 to mitotic spindl... | KEEP AS NON CORE | Summary: Retain mitotic-spindle association. Reason: The PKD2 paper includes spindle isolation from transfected HeLa cells; its endogenous double-staining image is porcine LLC-PK1. Independent human neural-progenitor imaging confirms DIAPH1 at mitotic spindles. |
| GO:0098793 presynapse | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Retain the process-to-location presynaptic inference. Reason: The source GO:0048488 is an experimentally grounded synaptic-vesicle retrieval process on the mouse donor, retained here as contextual. GO:0098793 is consistent with that presynaptic membrane-retrieval role. This electronic inference is not a separate direct human imaging experiment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: GO:0048488 SUPPORTS TRANSFER The retained synaptic-vesicle retrieval process supplies the contextual presynaptic-location inference; no direct human localization assay is manufactured. |
| GO:0101003 ficolin-1-rich granule membrane | TAS Reactome:R-HSA-6800426 | KEEP AS NON CORE | Summary: Retain the explicit ficolin-rich granule membrane entity. Reason: The R-HSA-6800426 input set 6800437 includes DIAPH1 entity 6801388 with reference O60610 and compartment GO:0101003. This source-specific location is retained without converting set membership into a general exocytosis mechanism. Supporting Evidence: Reactome:R-HSA-6800426 file:human/DIAPH1/DIAPH1-evidence-guide.md |
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Q: Which RNA species and DIAPH1 region underlie the UV-capture signal, and does that contact have a regulatory consequence beyond the detected association?
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