DNM1L encodes Drp1, a dynamin-family GTPase motor that divides mitochondria and peroxisomes. A soluble cytosolic pool is recruited to organelle membranes, where Drp1 oligomerization and GTP hydrolysis drive membrane constriction and fission. MFF and the mitochondrial adaptors MIEF1 and MIEF2 regulate recruitment, while peroxisomal division uses overlapping machinery. The protein contains a GTPase domain, a bundle-signalling element, an assembly stalk and a variable region affected by alternative splicing. Its membrane recruitment and assembly are controlled by interacting proteins and post-translational modifications. Beyond constitutive organelle division, Drp1 participates in context-dependent mitochondrial redistribution, apoptotic fragmentation and mitochondrial quality control; particular cellular and splice-product contexts also support microtubule and neuronal vesicle associations. Pathogenic DNM1L variants can disrupt organelle dynamics and cause severe neurological disease or optic atrophy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000266 mitochondrial fission | IBA GO_REF:0000033 | MODIFY | Reason: The literal PAINT IBD at PTN002480309 is on the authenticated DNM1L lineage in PTHR11566, with the human target among experimentally grounded descendants. There is no evidence of loss of fission in the target. Direct human Drp1 reconstitution resolves the performed step as mitochondrial membrane fission, a part of mitochondrial fission; refine the inherited process to that step rather than treating the IBA as a pairwise transfer. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002480309 SUPPORTS TRANSFER The literal GO:0000266 IBD is present at this node on the authenticated O00429 lineage in PTHR11566. The 736-residue target matches the family MSA exactly. Target-specific evidence supplies a finer scope without rejecting the inherited function. Proposed replacements: mitochondrial membrane fission |
| GO:0000266 mitochondrial fission | IDA PMID:20850011 Membrane remodeling induced by the dynamin-related protein D... | MODIFY | Reason: The source assays Drp1-dependent mitochondrial fragmentation and the effects of R247 substitutions in human HeLa cells. Its purified-protein liposome experiments separately demonstrate tethering and hemifusion during Bax activation, not complete membrane fusion or the GTP-dependent scission reaction itself. Independent scission reconstitution establishes the specific membrane-fission step represented by this broader process. Proposed replacements: mitochondrial membrane fission |
| GO:0000266 mitochondrial fission | IDA PMID:23530241 Interchangeable adaptors regulate mitochondrial dynamin asse... | MODIFY | Reason: The human Drp1 reconstitution and assembly experiments support its mechanical role in division. The historical variant-3 sequence is independently matched to the current 699-residue O00429-4 product. Refine the broad process to mitochondrial membrane fission; later direct tube-severing assays corroborate the scission step without proving literal twisting geometry. Proposed replacements: mitochondrial membrane fission |
| GO:0000266 mitochondrial fission | IMP PMID:18353969 The novel tail-anchored membrane protein Mff controls mitoch... | MODIFY | Reason: The Mff study experimentally places Drp1 in mitochondrial and peroxisomal division. The available source abstract supports that conclusion, while its complete original Methods were not recovered. Retain the positive curator assertion and refine the mitochondrial process using independently demonstrated Drp1 membrane scission; do not transfer Mff receptor activity to Drp1. Proposed replacements: mitochondrial membrane fission |
| GO:0000266 mitochondrial fission | IMP PMID:21149567 Mff is an essential factor for mitochondrial recruitment of ... | MODIFY | Reason: In human HeLa cells, Mff depletion reduces mitochondrial Drp1 foci and redistributes Drp1 to the soluble cytoplasmic pool; Mff-driven fragmentation depends on Drp1, also tested with mouse knockout fibroblasts. These results support the mitochondrial membrane-fission work of Drp1 rather than an Mff-like receptor function. Proposed replacements: mitochondrial membrane fission |
| GO:0000266 mitochondrial fission | IMP PMID:22265414 The mitochondrial phosphatase PGAM5 functions at the converg... | MODIFY | Reason: The complete cached abstract explicitly reports PGAM5-dependent Drp1 recruitment, activation of its GTPase activity and mitochondrial fragmentation during induced necrosis. The detailed original assays were not independently recovered. The positive target assertion agrees with the independently reconstituted membrane-scission function, which supplies the more precise process term; this does not assert a universal requirement for Drp1 in every necrosis pathway. Proposed replacements: mitochondrial membrane fission |
| GO:0000266 mitochondrial fission | IMP PMID:23349293 An actin-dependent step in mitochondrial fission mediated by... | MODIFY | Reason: In human U2OS cells the INF2 study follows mitochondrial Drp1 puncta and shows that Drp1 depletion or dominant-negative Drp1 blocks INF2-associated fragmentation. This supports the performed membrane-fission step; INF2 actin nucleation is not an activity of DNM1L. Supplementary construct details were not fully inspected. Proposed replacements: mitochondrial membrane fission |
| GO:0000266 mitochondrial fission | IMP PMID:23921378 Adaptor proteins MiD49 and MiD51 can act independently of Mf... | MODIFY | Reason: The source distinguishes mitochondrial recruitment of Drp1 by MiD proteins from its availability for peroxisomal division. Its engineered organelle-targeting constructs test recruitment mechanisms and are not natural DNM1L products. Retain mitochondrial fission and refine to the independently established membrane-scission step. Proposed replacements: mitochondrial membrane fission |
| GO:0000266 mitochondrial fission | IMP PMID:26992161 Postnatal microcephaly and pain insensitivity due to a de no... | MODIFY | Reason: The actual abstract reports impaired mitochondrial fission in patient fibroblasts and aberrant mitochondrial morphology after expression of the human disease allele, with peroxisomal morphology intact in that tested context. Complete original Methods were unavailable. The target-positive phenotype corroborates the established membrane-fission function; it does not establish that every DNM1L variant affects both organelles. Proposed replacements: mitochondrial membrane fission |
| GO:0000266 mitochondrial fission | IMP PMID:27145208 A novel de novo dominant negative mutation in DNM1L impairs ... | MODIFY | Reason: The paper combines human disease genetics with rescue and assembly experiments using a 699-residue mouse Drp1 construct in mouse cells. These experiments support membrane-fission function and variant-dependent disruption, without making the mouse construct a sequence-verified modern human isoform. Proposed replacements: mitochondrial membrane fission |
| GO:0000266 mitochondrial fission | IMP PMID:32484300 PINK1 phosphorylates Drp1(S616) to regulate mitophagy-indepe... | MODIFY | Reason: Human Drp1 expression and knockout/rescue experiments in HeLa cells connect PINK1-dependent Drp1 recruitment and phosphorylation with mitochondrial fragmentation. Drp1 performs the membrane-fission step; PINK1 kinase activity, Parkin dependence and the tested autophagy route should not be generalized to DNM1L catalysis. Proposed replacements: mitochondrial membrane fission |
| GO:0000266 mitochondrial fission | IMP PMID:37971521 GTPBP8 is required for mitoribosomal biogenesis and mitochon... | UNDECIDED | Reason: The imported source is the 2023 GTPBP8 mitoribosome paper. Its accessible main text did not resolve a target-specific Drp1 fission assay, and the supplemental file was not recovered. A separate 2024 study by overlapping authors, PMID:38587461, directly tests Drp1-dependent GTPBP8-associated fission. That is independent positive evidence, not verification that the imported 2023 source supplied this experiment. Preserve the curator assertion and original identifier pending source reconciliation. |
| GO:0003924 GTPase activity | EXP PMID:23977156 Functional mapping of human dynamin-1-like GTPase domain bas... | MODIFY | Reason: The source measures GTP hydrolysis by recombinant human DNM1L and engineered variants; its GG fusion and other engineered fragments are not additional natural products. The chemistry is correct. Independent human reconstitution couples GTP hydrolysis to membrane severing, supporting the more informative descendant GTPase motor activity. This refinement does not claim that each older source independently measured severing or resolved a twisting motion. Proposed replacements: GTPase motor activity |
| GO:0003924 GTPase activity | EXP PMID:9422767 Dymple, a novel dynamin-like high molecular weight GTPase la... | MODIFY | Reason: The historical dymple abstract establishes the human protein and its dynamin-related GTPase family, but the complete original enzyme-assay Methods were not recovered. The chemistry is correct. Independent human reconstitution couples GTP hydrolysis to membrane severing, supporting the more informative descendant GTPase motor activity. This refinement does not claim that each older source independently measured severing or resolved a twisting motion. Proposed replacements: GTPase motor activity |
| GO:0003924 GTPase activity | IBA GO_REF:0000033 | MODIFY | Reason: The literal GTPase IBD at ancestral PTN000170013 is on the authenticated target path; multiple direct descendant records, including the human target, ground the inherited chemistry. Target self-evidence is not circular. The chemistry is correct. Independent human reconstitution couples GTP hydrolysis to membrane severing, supporting the more informative descendant GTPase motor activity. This refinement does not claim that each older source independently measured severing or resolved a twisting motion. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000170013 SUPPORTS TRANSFER The literal GO:0003924 IBD is present at this node on the authenticated O00429 lineage in PTHR11566. The 736-residue target matches the family MSA exactly. Target-specific evidence supplies a finer scope without rejecting the inherited function. Proposed replacements: GTPase motor activity |
| GO:0003924 GTPase activity | IDA PMID:22265414 The mitochondrial phosphatase PGAM5 functions at the converg... | MODIFY | Reason: The actual source abstract explicitly reports activation of Drp1 GTPase activity by PGAM5-associated dephosphorylation during necrosis; complete original Methods remain unavailable. The chemistry is correct. Independent human reconstitution couples GTP hydrolysis to membrane severing, supporting the more informative descendant GTPase motor activity. This refinement does not claim that each older source independently measured severing or resolved a twisting motion. Proposed replacements: GTPase motor activity |
| GO:0003924 GTPase activity | IDA PMID:23530241 Interchangeable adaptors regulate mitochondrial dynamin asse... | MODIFY | Reason: Purified human Drp1 self-assembly stimulates GTP hydrolysis in the source; the historical 699-residue variant is sequence-matched to O00429-4. The chemistry is correct. Independent human reconstitution couples GTP hydrolysis to membrane severing, supporting the more informative descendant GTPase motor activity. This refinement does not claim that each older source independently measured severing or resolved a twisting motion. Proposed replacements: GTPase motor activity |
| GO:0003924 GTPase activity | IEA GO_REF:0000120 | MODIFY | Reason: The imported InterPro and RHEA sources describe dynamin-family guanine-nucleotide hydrolysis; the official target contains the mapped dynamin GTPase regions. The chemistry is correct. Independent human reconstitution couples GTP hydrolysis to membrane severing, supporting the more informative descendant GTPase motor activity. This refinement does not claim that each older source independently measured severing or resolved a twisting motion. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR001401 SUPPORTS TRANSFER This exact imported domain identifier occurs in the current official target record; the dynamin GTP-binding/hydrolysis capability is independently experimentally supported. InterPro:IPR003130 SUPPORTS TRANSFER This exact imported domain identifier occurs in the current official target record; the dynamin GTP-binding/hydrolysis capability is independently experimentally supported. RHEA:19669 SUPPORTS TRANSFER The imported GTP-hydrolysis reaction supplies the broad enzymatic assertion; direct human mechanochemical reconstitution supports the motor refinement. Proposed replacements: GTPase motor activity |
| GO:0005096 GTPase activator activity | IC PMID:25767741 Interaction with the effector dynamin-related protein 1 (Drp... | MARK AS OVER ANNOTATED | Summary: Rab-family effector binding does not establish GTPase activation. Reason: The actual experiments identify Drp1 as an effector preferentially associated with active Rab32-family proteins. They measure cross-linked association, membrane redistribution and mitochondrial morphology, not an increase in Rab-catalyzed GTP hydrolysis caused by Drp1. GO:0005096 requires binding to and increasing a GTPase's activity. The IC inference from small-GTPase and GTP-dependent binding therefore overstates the performed role. The positive binding observations remain supported in their own rows; this is not a claim that every possible Drp1-dependent GTPase-regulatory effect is absent. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PMID:25767741 SUPPORTS SOURCE BUT NOT TARGET The original supports Rab32βDrp1 association and an effector/recruitment role. It does not demonstrate that DNM1L increases Rab32 GTP hydrolysis as a GTPase activator. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12861026 The mitochondrial protein hFis1 regulates mitochondrial fiss... | KEEP AS NON CORE | Summary: DNM1L associates with FIS1 in cellular and purified-protein assays. Reason: The original includes cross-linked cellular co-immunoprecipitation and a purified bacterial Drp1/human FIS1 cytosolic-fragment binding experiment, with dynamin-2 as a specificity control. The truncated FIS1 construct and chemical cross-linking limit physiological interface claims but do not negate the positive interaction. Retain the generic binding assertion under the project policy; these experiments do not establish a separate signaling or enzymatic function for Drp1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18838687 Dephosphorylation by calcineurin regulates translocation of ... | MODIFY | Summary: Calcineurin interaction is protein phosphatase binding. Reason: The source explicitly reports that calcineurin normally interacts with Drp1 and dephosphorylates it in the calcium-dependent mitochondrial recruitment response. PPP3CA is a protein phosphatase, so protein phosphatase binding specifies the partner class without assigning phosphatase catalysis to Drp1. The complete abstract and curator assertion are positive; the full original methods were not recovered, so construct-level or purified-affinity claims are not made. Proposed replacements: protein phosphatase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19638400 SUMOylation of the mitochondrial fission protein Drp1 occurs... | MODIFY | Summary: UBC9 interaction is ubiquitin-like protein conjugating enzyme binding. Reason: The original human Drp1/UBC9 yeast two-hybrid experiments map UBC9 association to the GTPase and B regions, and the study independently demonstrates Drp1 SUMO conjugation. UBC9 is the SUMO-conjugating E2 enzyme, fitting the ubiquitin-like conjugating-enzyme binding class. This describes substrate-enzyme recognition, not SUMO-conjugating catalysis by Drp1. Proposed replacements: ubiquitin-like protein conjugating enzyme binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21149567 Mff is an essential factor for mitochondrial recruitment of ... | KEEP AS NON CORE | Summary: MFF recruits Drp1 and binds it in controlled cellular and in vitro assays. Reason: The paper detects cross-linked Drp1βMFF association in HeLa cells and with purified Drp1 and MFF lacking its membrane anchor. An assembly-defective Drp1 mutant loses binding and recruitment. The membrane-recruitment context is directly relevant to fission, but generic binding does not add an independent catalytic activity and is retained as non-core under project policy. Engineered MFF-CAAX recruitment does not establish normal plasma-membrane localization of Drp1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21149567 Mff is an essential factor for mitochondrial recruitment of ... | KEEP AS NON CORE | Summary: FIS1βDrp1 association is detectable under the source's milder extraction conditions. Reason: This source reports FIS1 co-precipitation with Drp1 after cross-linking and mild digitonin extraction, while the interaction is not detected under the stringent SDS condition that retains MFF association. That conditional positive result is not a negative interaction assertion. Independent purified-fragment work supports the pair, while neither study establishes a stable stoichiometric native complex. Retain positive generic binding as non-core. |
| GO:0005515 protein binding | IPI PMID:21217774 RAC3 is a pro-migratory co-activator of ERΞ±. | MODIFY | Summary: DNM1L binds the nuclear receptor ESR1 in orthogonal validation assays. Reason: Supplementary Table 1 explicitly identifies DNM1L clone BC024590: its in vitro interaction maps to the ERalpha ligand-binding domain and is estradiol dependent, whereas its mammalian two-hybrid interaction is reported as estradiol independent. These are target-specific confirmations beyond the discovery phage screen and support nuclear receptor binding. The detailed transcriptional co-activator and migration experiments concern RAC3; they are not transferred to DNM1L. The historical clone is not assigned to a current DNM1L isoform solely from its name. The publisher supplement was independently recovered and its table columns checked. The detailed purified-protein protocol in the main article is RAC3-specific, so no purified full-length DNM1L protocol or endogenous transcriptional co-activator role is inferred. Proposed replacements: nuclear receptor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21508961 MiD49 and MiD51, new components of the mitochondrial fission... | KEEP AS NON CORE | Summary: MIEF2/MiD49 is a positively supported Drp1-binding recruitment factor. Reason: The source abstract reports Drp1 recruitment by MiD49/51. The exact MINT records additionally document a human MiD49βDrp1 two-hybrid pair and a cross-linking association in HeLa cells; a separate microscopy record is only colocalization. Retain the positive physical association as non-core generic binding. The unavailable complete original methods limit finer construct and affinity claims, and overexpression-dependent mitochondrial elongation is not evidence against the interaction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21701560 Human MIEF1 recruits Drp1 to mitochondrial outer membranes a... | KEEP AS NON CORE | Summary: MIEF1/MiD51 binds and recruits Drp1. Reason: The actual original shows co-immunoprecipitation of endogenous Drp1 with MIEF1 in human 293T cells, recruitment of wild-type and K38A Drp1, and MIEF1 deletion mutants that lose or weaken association. Its oligomerization and phosphorylation assays are distinct from the binding assay. Retain the positive interaction as non-core generic binding; the overexpression-induced fusion phenotype does not mean that the binding itself is false. Supporting Evidence: PMID:21701560 Co-IP showed that MIEF1 binds to wild-type Myc-Drp1, Myc-Drp1S637A and Myc-Drp1S637D |
| GO:0005515 protein binding | IPI PMID:21822277 RALA and RALBP1 regulate mitochondrial fission at mitosis. | MODIFY | Summary: Drp1 engages the RALBP1 mitotic signaling scaffold. Reason: The original supports a RalAβRALBP1βcyclin B/CDK1βDrp1 assembly in cross-linked mitotic HeLa mitochondrial extracts. Purified RALBP1 increases cyclin B/CDK1 phosphorylation of the Drp1 C-terminal fragment, supporting the partner's scaffold role beyond complex membership alone. Scaffold protein binding is therefore an informative refinement. The cellular association is not a purified full-length binding-affinity measurement, and it does not give Drp1 the scaffold or kinase activity. Proposed replacements: scaffold protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22228096 LRRK2 regulates mitochondrial dynamics and function through ... | MODIFY | Summary: LRRK2 association specifies protein serine/threonine kinase binding. Reason: The positive abstract and exact reciprocal SH-SY5Y co-immunoprecipitation records support the Drp1βLRRK2 pair; disease-associated and kinase/GTP-binding mutants alter association. The complete original methods remain unavailable. LRRK2 is a serine/threonine kinase; the replacement classifies the binding partner and does not assign kinase activity or prove activation by Drp1. Proposed replacements: protein serine/threonine kinase binding |
| GO:0005515 protein binding | IPI PMID:22367970 Abnormal interaction between the mitochondrial fission prote... | MODIFY | Summary: The reported phosphorylated-tau association supports tau protein binding. Reason: The complete abstract explicitly describes co-immunoprecipitation and immunofluorescence evidence for Drp1βphosphorylated tau association in human Alzheimer brain and mouse disease models. Tau protein binding identifies the actual partner rather than generic protein binding. Retain the disease-associated and complex-association scope: purified direct affinity and a constitutive physiological complex were not independently established, and the full original methods were unavailable. Proposed replacements: tau protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22639965 Leucine-rich repeat kinase 2 disturbs mitochondrial dynamics... | MODIFY | Summary: LRRK2 association specifies protein serine/threonine kinase binding. Reason: The positive abstract reports endogenous neuronal association. Exact curated human HEK293T co-immunoprecipitation records separately document the human pair and constructs; neuronal colocalization is not treated as a binding assay. The complete original methods remain unavailable. LRRK2 is a serine/threonine kinase; the replacement classifies the binding partner and does not assign kinase activity or prove activation by Drp1. Proposed replacements: protein serine/threonine kinase binding |
| GO:0005515 protein binding | IPI PMID:23283981 Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mito... | KEEP AS NON CORE | Summary: MiD49/MIEF2 association is supported in the tested ortholog construct system. Reason: The original amplifies MiD and Drp1 variant-2 constructs from a mouse MEF cDNA library and tests cross-linked co-immunoprecipitation in human 293T cells. It explicitly uses human residue labels for corresponding mouse phosphorylation sites. Thus the paper supports the conserved association, not a direct assay of every human natural product. Independent human-source recruitment/binding evidence supports the gene-level claim, retained as non-core generic binding. |
| GO:0005515 protein binding | IPI PMID:23283981 Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mito... | KEEP AS NON CORE | Summary: MiD51/MIEF1 association is supported in the tested ortholog construct system. Reason: The original amplifies MiD and Drp1 variant-2 constructs from a mouse MEF cDNA library and tests cross-linked co-immunoprecipitation in human 293T cells. It explicitly uses human residue labels for corresponding mouse phosphorylation sites. Thus the paper supports the conserved association, not a direct assay of every human natural product. Independent human-source recruitment/binding evidence supports the gene-level claim, retained as non-core generic binding. |
| GO:0005515 protein binding | IPI PMID:23813973 Inhibition of excessive mitochondrial fission reduced aberra... | MODIFY | Summary: LRRK2 association specifies protein serine/threonine kinase binding. Reason: The abstract reports binding and phosphorylation of Drp1 by LRRK2 G2019S, and the exact human HEK293T co-immunoprecipitation record is positive. Full methods were not recovered, so the historical phosphorylation coordinate is not independently remapped here. LRRK2 is a serine/threonine kinase; the replacement classifies the binding partner and does not assign kinase activity or prove activation by Drp1. Proposed replacements: protein serine/threonine kinase binding |
| GO:0005515 protein binding | IPI PMID:24282027 Functional interaction of Parkinson's disease-associated LRR... | MODIFY | Summary: LRRK2 association specifies protein serine/threonine kinase binding. Reason: The actual original reports reciprocal co-immunoprecipitation of human Myc-Drp1 and full-length human LRRK2 in HEK293T cells, with separate endogenous mouse-brain confirmation. The K38A binding result is distinct from catalytic assays. LRRK2 is a serine/threonine kinase; the replacement classifies the binding partner and does not assign kinase activity or prove activation by Drp1. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24550280 Large-scale interaction profiling of PDZ domains through pro... | KEEP AS NON CORE | Summary: A Drp1-derived peptide binds SCRIB PDZ domains in the discovery assay. Reason: Exact MINT records identify DNM1L and SCRIB PDZ-region baits in proteomic peptide-phage display. The actual source discussion emphasizes that this assay does not establish cellular spatial or temporal coincidence. Preserve the positive peptide interaction as non-core under project policy; no endogenous Drp1βSCRIB complex or Drp1 signaling-scaffold function was independently established. The cached original contains the discussion but omits the operative Results/Methods, so those sections are not claimed as read. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26358295 COX assembly factor ccdc56 regulates mitochondrial morpholog... | KEEP AS NON CORE | Summary: The source-specific curated pair is Drp1βMFF. Reason: The paper foregrounds CCDC56/COA3, but the exact human HeLa cross-linking record is a positive Q9GZY8 MFFβO00429 Drp1 association. This is not evidence that the row accidentally names CCDC56 or ATAD3A. Independent targeted cellular and purified-fragment MFF assays corroborate the pair. Retain generic binding as non-core, with the present paper's complete original methods still unavailable. |
| GO:0005515 protein binding | IPI PMID:26618722 Parkinson's disease-associated mutant VPS35 causes mitochond... | KEEP AS NON CORE | Summary: VPS35 binds Drp1 during regulated turnover of mitochondrial Drp1 assemblies. Reason: The original shows yeast two-hybrid interaction, reciprocal endogenous co-immunoprecipitation in human M17 cells, and mitochondrial-fraction association, with disease and oxidative-stress modulation. This is positive target-specific binding and cannot be removed merely because the term is generic. Retain it as non-core; VPS35-dependent recycling of Drp1 complexes does not by itself assign retromer cargo-transport activity to Drp1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27059175 SAMM50 Affects Mitochondrial Morphology through the Associat... | KEEP AS NON CORE | Summary: SAMM50βDrp1 binding is supported by cellular and fragment assays. Reason: The source abstract reports both cellular and in vitro interaction. Exact curated records include reciprocal human HeLa co-immunoprecipitation and an in vitro SAMM50-region/Drp1 interaction. Retain the positive association as non-core generic binding. Full original methods were unavailable; SAM-complex protein-assembly activity is not transferred to Drp1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29464060 Drp1/Fis1 interaction mediates mitochondrial dysfunction, bi... | KEEP AS NON CORE | Summary: The MiD49/MIEF2 association remains supported in the adaptor comparison. Reason: The original compares Drp1 co-immunoprecipitation with all four adaptors in human SH-SY5Y cells. Amyloid-beta increases the FIS1 association, while association with the other adaptors shows no reported increase; unchanged association is not absence. The methods use cross-linking for cellular immunoprecipitation and do not establish purified binary affinities. Retain this positive, context-dependent association as non-core generic binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29464060 Drp1/Fis1 interaction mediates mitochondrial dysfunction, bi... | KEEP AS NON CORE | Summary: The MFF association remains supported in the adaptor comparison. Reason: The original compares Drp1 co-immunoprecipitation with all four adaptors in human SH-SY5Y cells. Amyloid-beta increases the FIS1 association, while association with the other adaptors shows no reported increase; unchanged association is not absence. The methods use cross-linking for cellular immunoprecipitation and do not establish purified binary affinities. Retain this positive, context-dependent association as non-core generic binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29464060 Drp1/Fis1 interaction mediates mitochondrial dysfunction, bi... | KEEP AS NON CORE | Summary: The MiD51/MIEF1 association remains supported in the adaptor comparison. Reason: The original compares Drp1 co-immunoprecipitation with all four adaptors in human SH-SY5Y cells. Amyloid-beta increases the FIS1 association, while association with the other adaptors shows no reported increase; unchanged association is not absence. The methods use cross-linking for cellular immunoprecipitation and do not establish purified binary affinities. Retain this positive, context-dependent association as non-core generic binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29464060 Drp1/Fis1 interaction mediates mitochondrial dysfunction, bi... | KEEP AS NON CORE | Summary: The FIS1 association remains supported in the adaptor comparison. Reason: The original compares Drp1 co-immunoprecipitation with all four adaptors in human SH-SY5Y cells. Amyloid-beta increases the FIS1 association, while association with the other adaptors shows no reported increase; unchanged association is not absence. The methods use cross-linking for cellular immunoprecipitation and do not establish purified binary affinities. Retain this positive, context-dependent association as non-core generic binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29541021 The LRRK2 Variant E193K Prevents Mitochondrial Fission Upon ... | MODIFY | Summary: LRRK2 association specifies protein serine/threonine kinase binding. Reason: The original combines endogenous mouse-brain association, human HEK293 construct pull-downs, and LRRK2 armadillo-domain capture from brain extract. These support the interaction and its sensitivity to the E193K variant, without establishing a purified equilibrium affinity. LRRK2 is a serine/threonine kinase; the replacement classifies the binding partner and does not assign kinase activity or prove activation by Drp1. Proposed replacements: protein serine/threonine kinase binding |
| GO:0005515 protein binding | IPI PMID:30914652 ATAD3A oligomerization causes neurodegeneration by coupling ... | MODIFY | Summary: Direct ATAD3A association specifies ATPase binding. Reason: The original combines Drp1 affinity purification from human HD-derived neurons, human and mouse tissue/cell co-immunoprecipitation, and in vitro GST-Drp1 binding to cell-free-produced, FLAG-purified ATAD3A without a cross-linker. ATAD3A is an ATPase, so ATPase binding specifies the partner class without transferring ATP hydrolysis to Drp1. The imported partner identity is retained; Q9NVI7-2 is the current displayed 586-residue ATAD3A product, independently matched to its official FASTA. This does not infer equal binding or activity for all ATAD3A or DNM1L products. Proposed replacements: ATPase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:30914652 ATAD3A oligomerization causes neurodegeneration by coupling ... | MODIFY | Summary: Direct ATAD3A association specifies ATPase binding. Reason: The original combines Drp1 affinity purification from human HD-derived neurons, human and mouse tissue/cell co-immunoprecipitation, and in vitro GST-Drp1 binding to cell-free-produced, FLAG-purified ATAD3A without a cross-linker. ATAD3A is an ATPase, so ATPase binding specifies the partner class without transferring ATP hydrolysis to Drp1. The imported partner identity is retained; Q9NVI7-2 is the current displayed 586-residue ATAD3A product, independently matched to its official FASTA. This does not infer equal binding or activity for all ATAD3A or DNM1L products. Proposed replacements: ATPase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31046837 Parkinson's disease-associated LRRK2-G2019S mutant acts thro... | MODIFY | Summary: LRRK2 association specifies protein serine/threonine kinase binding. Reason: The source supplies a positive spoke-expanded LRRK2βDNM1L co-immunoprecipitation/MS record from human HEK293T cells exposed to alpha-synuclein. It does not itself isolate a binary interface. Independent reciprocal targeted Drp1βLRRK2 co-immunoprecipitation supports the same partner-specific binding class; the source's SERCA/ER-stress mechanism is not transferred to Drp1. LRRK2 is a serine/threonine kinase; the replacement classifies the binding partner and does not assign kinase activity or prove activation by Drp1. Proposed replacements: protein serine/threonine kinase binding |
| GO:0005515 protein binding | IPI PMID:9731200 Human dynamin-like protein interacts with the glycogen synth... | MODIFY | Summary: Human GSK3B recognition specifies protein serine/threonine kinase binding. Reason: The source abstract explicitly identifies human GSK3B as the two-hybrid bait and maps the human HdynIV/Drp1 interaction to its C-terminal region. This supports a kinase-partner binding class, not kinase activity by Drp1 or the paper's speculative developmental signaling role. The full original methods and exact historical construct sequence were not recovered. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | ACCEPT | Reason: The mapped dynamin/GTPase regions and recombinant nucleotide-binding experiments support GTP binding. Binding is a true component of the mechanochemical cycle, not a substitute for ATP binding, and is not replaced across ontology branches by the motor term. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR001401 SUPPORTS TRANSFER This exact imported domain identifier occurs in the current official target record; the dynamin GTP-binding/hydrolysis capability is independently experimentally supported. InterPro:IPR003130 SUPPORTS TRANSFER This exact imported domain identifier occurs in the current official target record; the dynamin GTP-binding/hydrolysis capability is independently experimentally supported. InterPro:IPR030381 SUPPORTS TRANSFER This exact imported domain identifier occurs in the current official target record; the dynamin GTP-binding/hydrolysis capability is independently experimentally supported. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | MODIFY | Reason: The literal cytoplasm IBD at PTN000170013 is present on the authenticated target lineage and has experimental descendant grounding, including human DNM1L. Refine to the supported nonexclusive cytosolic, mitochondrial, peroxisomal, ER/Golgi, perinuclear and synaptic-vesicle-membrane pools that are typed descendants of cytoplasm. The separately supported microtubule and clathrin-coated-pit pools are retained in their own rows because the checked ontology does not place those terms under cytoplasm. Assay, organism and product limits remain source-specific; no universal distribution across all natural products is asserted. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000170013 SUPPORTS TRANSFER The literal GO:0005737 IBD is present at this node on the authenticated O00429 lineage in PTHR11566. The 736-residue target matches the family MSA exactly. Target-specific evidence supplies a finer scope without rejecting the inherited function. Proposed replacements: cytosol mitochondrial outer membrane peroxisomal membrane endoplasmic reticulum membrane Golgi apparatus perinuclear region of cytoplasm synaptic vesicle membrane Supporting Evidence: |
| GO:0005737 cytoplasm | IDA PMID:12618434 The dynamin-like GTPase DLP1 is essential for peroxisome div... | MODIFY | Reason: The source establishes a predominantly soluble cytoplasmic DLP1 pool together with recruitment to human peroxisomal membranes. Preserve both pools using cytosol and peroxisomal membrane, rather than interpreting cytoplasm as exclusively soluble or assigning every signal to mitochondria. Proposed replacements: cytosol peroxisomal membrane |
| GO:0005737 cytoplasm | IDA PMID:21149567 Mff is an essential factor for mitochondrial recruitment of ... | MODIFY | Reason: The original HeLa experiments show that Mff depletion shifts Drp1 from mitochondrial foci into the diffuse cytoplasmic pool, with fractionation supporting the redistribution. Cytosol and mitochondrial outer membrane capture these complementary pools; neither location is exclusive. Proposed replacements: cytosol mitochondrial outer membrane Supporting Evidence: PMID:21149567 Drp1 foci on the mitochondria was clearly decreased and rather was dispersed throughout the cytoplasm in Mff RNAi cells |
| GO:0005737 cytoplasm | IDA PMID:23349293 An actin-dependent step in mitochondrial fission mediated by... | MODIFY | Reason: The human U2OS study describes diffuse cytoplasmic Drp1 and puncta associated with mitochondria in the INF2 experiments. Refine to cytosol and mitochondrial outer membrane using these observations and independently resolved Drp1 membrane recruitment, without attributing INF2 actin-polymerization activity to DNM1L. Proposed replacements: cytosol mitochondrial outer membrane |
| GO:0005737 cytoplasm | IMP PMID:28969390 Mutations in DNM1L, as in OPA1, result in dominant optic atr... | MODIFY | Reason: The actual abstract reports DNM1L aggregates in the cytoplasm and on the highly tubulated mitochondrial network of patient fibroblasts; whole original Methods were unavailable. The established cytosolic and mitochondrial-outer-membrane pools supply more specific locations, but the precise physical compartment of each disease-associated aggregate is not separately resolved and is not claimed to be a wild-type steady state. Proposed replacements: cytosol mitochondrial outer membrane Supporting Evidence: PMID:28969390 revealed physiological abundance and homo-polymerization of DNM1L, forming aggregates in the cytoplasm and on highly tubulated mitochondrial network |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | MODIFY | Reason: The exact MitoCoP Table S1 target is O00429 in protein groups 2536/2538 and the DRP1 gene row. Both groups enter MitoCoP through literature pool 4; the study does not newly validate a DNM1L import or subcompartment assay. The mitochondrial claim is sound, with outer-membrane precision supplied by independent targeted experiments. Proposed replacements: mitochondrial outer membrane |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | MODIFY | Reason: The mitochondrial IBD at PTN002480309 is on the authenticated DNM1L lineage, with target experimental evidence among the descendants. The membrane-associated fission pool is more specifically at the mitochondrial outer membrane. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002480309 SUPPORTS TRANSFER The literal GO:0005739 IBD is present at this node on the authenticated O00429 lineage in PTHR11566. The 736-residue target matches the family MSA exactly. Target-specific evidence supplies a finer scope without rejecting the inherited function. Proposed replacements: mitochondrial outer membrane |
| GO:0005739 mitochondrion | IDA PMID:11514614 Dynamin-related protein Drp1 is required for mitochondrial d... | MODIFY | Reason: The original distinguishes endogenous Drp1 staining in COS-7 cells from bovine-brain biochemical fractionation. Both show a large cytosolic pool and a smaller mitochondrial pool. Human Drp1 transgenes were tested separately in COS-7/C2C12 cells; independent human recruitment studies support the outer-membrane refinement. Proposed replacements: mitochondrial outer membrane |
| GO:0005739 mitochondrion | IDA PMID:21822277 RALA and RALBP1 regulate mitochondrial fission at mitosis. | MODIFY | Reason: The RALA/RALBP1 study measures mitotic recruitment of Drp1 to mitochondrial fractions and the functional fission complex. This is the outer-membrane fission pool, not a mitochondrial matrix enzyme or a Ral GTPase activity of Drp1. Proposed replacements: mitochondrial outer membrane |
| GO:0005739 mitochondrion | IDA PMID:22265414 The mitochondrial phosphatase PGAM5 functions at the converg... | MODIFY | Reason: The actual source abstract explicitly reports recruitment of Drp1 by mitochondrial PGAM5 during induced necrosis. Complete original localization controls were unavailable; independent targeted evidence resolves the positive mitochondrial pool to the outer membrane. Proposed replacements: mitochondrial outer membrane Supporting Evidence: PMID:22265414 PGAM5S recruited the mitochondrial fission factor Drp1 and activated its GTPase activity by dephosphorylating the serine 637 site of Drp1 |
| GO:0005739 mitochondrion | IDA PMID:23349293 An actin-dependent step in mitochondrial fission mediated by... | MODIFY | Reason: The human U2OS INF2 study directly observes mitochondrial Drp1 puncta; independent recruitment and membrane-scission evidence resolves their compartment as the outer membrane. Supplementary construct boundaries were not fully inspected. Proposed replacements: mitochondrial outer membrane |
| GO:0005739 mitochondrion | IDA PMID:23530241 Interchangeable adaptors regulate mitochondrial dynamin asse... | MODIFY | Reason: Human Drp1 membrane assembly and GTPase experiments are consistent with the outer-membrane fission apparatus, corroborated by direct cellular localization. The recombinant preparation itself is not an organelle-fractionation experiment. Proposed replacements: mitochondrial outer membrane |
| GO:0005739 mitochondrion | IDA PMID:23921378 Adaptor proteins MiD49 and MiD51 can act independently of Mf... | MODIFY | Reason: The MiD study distinguishes mitochondrial Drp1 recruitment from depletion of the available peroxisomal pool. Engineered targeting experiments are kept separate from endogenous mitochondrial localization and natural products. Proposed replacements: mitochondrial outer membrane |
| GO:0005739 mitochondrion | IDA PMID:24599962 Phosphatidic acid (PA)-preferring phospholipase A1 regulates... | MODIFY | Reason: The HeLa DDHD1 experiments retain positive Drp1 puncta at mitochondrial constrictions even when the tested perturbation does not change recruitment. An unchanged response is not a negative localization result. Proposed replacements: mitochondrial outer membrane Supporting Evidence: PMID:24599962 The enlarged images show that Drp1 was localized in constricted regions of elongated mitochondria |
| GO:0005739 mitochondrion | IDA PMID:26618722 Parkinson's disease-associated mutant VPS35 causes mitochond... | MODIFY | Reason: The study resolves mitochondrial DLP1 assemblies in human M17 cells separately from DLP1 carried by mitochondrion-derived vesicles. Outer membrane describes the mitochondrial fission pool; the vesicular cargo pool is retained separately and is not a matrix localization. Proposed replacements: mitochondrial outer membrane |
| GO:0005739 mitochondrion | IDA PMID:29307555 Vps13D Encodes a Ubiquitin-Binding Protein that Is Required ... | MODIFY | Reason: Human VPS13D-knockout HeLa cells show Drp1 puncta associated with TOM20-labelled mitochondria. The source also contains separate fly experiments, which are not treated as human construct assays. Proposed replacements: mitochondrial outer membrane |
| GO:0005739 mitochondrion | IDA PMID:37971521 GTPBP8 is required for mitoribosomal biogenesis and mitochon... | UNDECIDED | Reason: The imported 2023 GTPBP8 source did not yield an adjudicable DNM1L localization assay in the accessible main text, and its supplement remains unavailable. The separate 2024 GTPBP8 paper measures Drp1 recruitment to mitochondria directly, but that does not authenticate the experiment attributed here to PMID:37971521. Retain the positive source assertion as unresolved rather than declaring the protein absent from mitochondria. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | MODIFY | Reason: The source combines a mitochondrial subcellular-location mapping with an ARBA record. The current ARBA00026962 conditions do not reproduce the old assignment on the current target record, so the exact historical rule match remains unresolved; this does not refute the extensive direct evidence for mitochondrial-outer-membrane recruitment. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: ARBA:ARBA00026962 UNRESOLVED The current 380-branch rule has no matching branch on the current target record. Historical matching remains unresolved; direct human localization independently supports the mitochondrial claim and outer-membrane refinement. UniProtKB:Q8K1M6 SUPPORTS TRANSFER Current mouse mitochondrial annotations include direct observations; independent human experiments resolve the target outer-membrane pool. Proposed replacements: mitochondrial outer membrane |
| GO:0005739 mitochondrion | IMP PMID:28969390 Mutations in DNM1L, as in OPA1, result in dominant optic atr... | MODIFY | Reason: The complete cached abstract describes human patient-fibroblast DNM1L aggregates on a tubulated mitochondrial network as well as cytoplasmic aggregates. Complete original Methods were unavailable. Independent targeted membrane localization resolves the gene-level mitochondrial pool without claiming that every disease aggregate has the same topology. Proposed replacements: mitochondrial outer membrane |
| GO:0005741 mitochondrial outer membrane | EXP PMID:27145933 FUNDC1 regulates mitochondrial dynamics at the ER-mitochondr... | ACCEPT | Reason: The source follows human Drp1 recruitment under hypoxia, including a MAM-associated stage and subsequent accumulation on mitochondria. This supports a mitochondrial outer-membrane pool without excluding the transient ER-associated stage. Supporting Evidence: |
| GO:0005741 mitochondrial outer membrane | EXP PMID:28969390 Mutations in DNM1L, as in OPA1, result in dominant optic atr... | ACCEPT | Reason: The actual abstract reports DNM1L on the mitochondrial network of human patient fibroblasts. The full original localization controls were not recovered; the curator-assigned outer-membrane interpretation is independently well supported. |
| GO:0005741 mitochondrial outer membrane | IDA PMID:21149567 Mff is an essential factor for mitochondrial recruitment of ... | ACCEPT | Reason: Targeted human HeLa microscopy, fractionation and recruitment experiments establish mitochondrial Drp1 foci and an Mff-dependent outer-membrane pool; mouse knockout assays are a separate functional test. Supporting Evidence: |
| GO:0005741 mitochondrial outer membrane | IDA PMID:26122121 Signal transducer and activator of transcription 2 deficienc... | ACCEPT | Reason: The original patient/control fibroblast study visualizes Drp1 with TOM20. The lack of a significant STAT2-dependent localization change does not negate the observed outer-membrane pool. Supporting Evidence: PMID:26122121 DRP1 localization was carried out by labelling the mitochondria with TOM20, DRP1 with FITC conjugated secondary antibody |
| GO:0005741 mitochondrial outer membrane | IDA PMID:27145208 A novel de novo dominant negative mutation in DNM1L impairs ... | ACCEPT | Reason: The primary source combines human disease observations with mouse Drp1 constructs in mouse fibroblasts. Digitonin-assisted localization of the tested constructs resolves mitochondrial puncta; independent human evidence corroborates the conserved outer-membrane pool. |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000120 | ACCEPT | Reason: The official subcellular-location mapping is supported by targeted Drp1 mitochondrial recruitment and fission studies. Drp1 is peripheral to the membrane; it is not inferred to be an integral membrane protein. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8K1M6 SUPPORTS TRANSFER Current mouse outer-membrane annotations are positive and independent human localization supports the same compartment. UniProtKB-SubCell:SL-0172 SUPPORTS TRANSFER Official outer-membrane mapping agrees with direct human Drp1 localization. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-351948 | ACCEPT | Reason: The exact Reactome reaction R-HSA-351948 moves human DNM1L residues 1β736 from entity 351943 in cytosol to entity 351942 on the mitochondrial outer membrane. BAP31 cleavage and calcium signalling provide the recruitment context; DNM1L is not the protease or the cleaved BAP31 substrate. |
| GO:0005777 peroxisome | EXP PMID:12499366 Dynamin-like protein 1 is involved in peroxisomal fission. | MODIFY | Reason: The source supports DLP1 association with peroxisomal membranes in human HepG2 cells and corresponding fractionation experiments, with rat material distinguished where used. Peroxisomal membrane is more precise than the whole organelle. Proposed replacements: peroxisomal membrane |
| GO:0005777 peroxisome | IDA PMID:12618434 The dynamin-like GTPase DLP1 is essential for peroxisome div... | MODIFY | Reason: The source directly reports DLP1 on peroxisomal membranes and its role in division. This is recruitment to the organelle boundary, not a peroxisomal-matrix enzyme; PEX11B recruitment does not by itself establish purified binary binding. Proposed replacements: peroxisomal membrane |
| GO:0005777 peroxisome | IEA GO_REF:0000120 | MODIFY | Reason: The imported mouse ortholog has direct peroxisome annotations, including the mouse isoform experiments in PMID:29853636. Current ARBA00028589 does not reproduce the historical target match, but that uncertainty does not negate the independently demonstrated human peroxisomal-membrane pool. No equivalence of every mouse and human splice product is assumed. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: ARBA:ARBA00028589 UNRESOLVED The current 59-branch rule has no matching branch on the current target record. Historical matching remains unresolved; human peroxisomal-membrane observations and the explicit mouse donor are retained. UniProtKB:Q8K1M6 SUPPORTS TRANSFER Current mouse peroxisome evidence includes PMID:29853636, which assays cloned mouse isoforms, not all human products. UniProtKB-SubCell:SL-0204 SUPPORTS TRANSFER Official peroxisomal mapping agrees with direct human membrane recruitment. Proposed replacements: peroxisomal membrane |
| GO:0005777 peroxisome | IMP PMID:23921378 Adaptor proteins MiD49 and MiD51 can act independently of Mf... | MODIFY | Reason: The source tests how mitochondrial sequestration of Drp1 affects peroxisomal division and distinguishes engineered MiD/FKBP targeting from native localization. Independent human DLP1 membrane-localization experiments justify the more specific peroxisomal-membrane term. Proposed replacements: peroxisomal membrane |
| GO:0005783 endoplasmic reticulum | IDA NOT PMID:11514614 Dynamin-related protein Drp1 is required for mitochondrial d... | ACCEPT | Reason: This is a NOT annotation. Endogenous Drp1 staining in COS-7 cells did not colocalize with ribophorin-I under the tested methanol/acetone fixation conditions. The antibody was raised against human Drp1, which does not make the endogenous COS-7 protein human. Separate bovine-brain fractionation argued against an ER-bound high-speed pellet. Retain the curator-backed negative assertion with these species and assay limits; it does not establish universal exclusion of human DNM1L from ER contacts. Supporting Evidence: |
| GO:0005783 endoplasmic reticulum | IDA PMID:9472031 A novel dynamin-like protein associates with cytoplasmic ves... | MODIFY | Reason: The actual original uses rat DLP1 and rat liver material, with ER-marker alignment and immunogold/fractionation evidence for an ER-associated pool. Refine the positive compartment to ER membrane, preserving its organism and assay scope. This differs from the later COS-7 endogenous ER-negative experiment in PMID:11514614 and is not proof of universal ER localization. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: |
| GO:0005789 endoplasmic reticulum membrane | TAS PMID:25767741 Interaction with the effector dynamin-related protein 1 (Drp... | KEEP AS NON CORE | Reason: The Rab32 paper supports a condition-dependent ER-associated Drp1 pool in a cellular recruitment/signalling context. It does not make DNM1L an ER-resident integral protein, a Rab GAP, or an ER-specific catalytic core. The actual Rab32 association and mitochondrial recruitment functions remain distinct. Supporting Evidence: PMID:25767741 they sequester their effector Drp1 to block mitochondria fission dependent on their own extent of localization to the ER and the MAM |
| GO:0005794 Golgi apparatus | EXP PMID:9348079 Identification and subcellular localization of a novel mamma... | UNDECIDED | Reason: The actual source abstract describes human DVLP in diffuse and perinuclear patterns that were not superimposable on the tested Golgi and other organelle markers. Complete original Methods and all target-specific experiments were not recovered, so this discrepancy is not sufficient to remove or declare misattributed the curator assertion. Other papers support a cell-type-dependent Golgi pool, but they do not verify this particular source. |
| GO:0005794 Golgi apparatus | EXP PMID:9570752 Identification and functional characterization of a novel hu... | KEEP AS NON CORE | Reason: The actual abstract reports human Drp1 expressed in CHO cells in a perinuclear region labelled by the Golgi marker C5-DMB-Cer and an ER marker. Preserve this positive localization as a contextual pool, with the whole original assay controls still unavailable. It is not evidence that all Drp1 is Golgi-resident. Supporting Evidence: |
| GO:0005794 Golgi apparatus | IDA PMID:20688057 Dynamin-like protein 1 at the Golgi complex: a novel compone... | KEEP AS NON CORE | Reason: The actual abstract explicitly reports DLP1 at the Golgi in some but not all tested cell lines, and differential effects on apical versus basolateral cargo transport. Preserve that contextual Golgi pool. The full original Methods were not recovered, so no unverified species or construct details are supplied. Supporting Evidence: PMID:20688057 DLP1 localized to the Golgi complex in some but not all cell lines tested, thus explaining controversial reports on its cellular distribution |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | KEEP AS NON CORE | Reason: The UniProt Golgi mapping is supported by the explicit positive localization in PMID:20688057 and the earlier CHO-expression result, while other sources report negative marker overlap. Retain a conditional Golgi pool without asserting a constitutive Golgi residence or dismissing the source-specific negative observations. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0132 SUPPORTS TRANSFER Official Golgi mapping is corroborated by the explicit cell-context observations in PMID:20688057 and PMID:9570752. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Reason: The official HPA target record matches ENSG00000087470/O00429 and reports supported cytosolic staining in its ICC/IF records, with an additional vesicular summary for another antibody. The data record was inspected; microscopy pixels were not independently interpreted. Cytosol is an established functional source pool for membrane recruitment. Supporting Evidence: HPA:ENSG00000087470 |
| GO:0005829 cytosol | IDA PMID:22265414 The mitochondrial phosphatase PGAM5 functions at the converg... | ACCEPT | Reason: The source abstract explicitly describes Drp1 activation and mitochondrial recruitment during induced necrosis; complete fractionation Methods were not recovered. Its curator-assigned cytosolic pool agrees with independently observed endogenous human Drp1 before recruitment, so retain the positive localization with that access limit. |
| GO:0005829 cytosol | IDA PMID:23921378 Adaptor proteins MiD49 and MiD51 can act independently of Mf... | ACCEPT | Reason: The source distinguishes cytosolic Drp1 from recruited mitochondrial and peroxisomal pools. The soluble pool remains part of the recruitment cycle, even when engineered targeting proteins redistribute the molecule; it is not an exclusive location. Supporting Evidence: |
| GO:0005829 cytosol | IDA PMID:37971521 GTPBP8 is required for mitoribosomal biogenesis and mitochon... | UNDECIDED | Reason: The accessible 2023 GTPBP8 main text did not resolve the imported cytosolic Drp1 experiment, and its supplement was unavailable. The separate 2024 GTPBP8 paper directly shows diffuse cytosolic Drp1 and altered mitochondrial recruitment. Preserve that independent corroboration while leaving this source-specific assertion unresolved. |
| GO:0005829 cytosol | IEA GO_REF:0000120 | ACCEPT | Reason: The current ARBA00029243 target branch matches both recorded FunFam signatures and the eukaryotic taxon condition. The rule-supported cytosolic pool agrees with independent HPA and targeted human Drp1 observations; the rule does not imply exclusive cytosolic residence. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00029243 SUPPORTS TRANSFER Current branch 78 matches the target FunFam signatures and Eukaryota condition; independent human observations support cytosol. UniProtKB:Q8K1M6 SUPPORTS TRANSFER Mouse cytosol supports the conserved recruitment pool, independently corroborated in human cells. UniProtKB-SubCell:SL-0091 SUPPORTS TRANSFER Official cytosol mapping agrees with the HPA record and endogenous human Drp1 observations. Supporting Evidence: |
| GO:0005829 cytosol | IMP PMID:11514614 Dynamin-related protein Drp1 is required for mitochondrial d... | ACCEPT | Reason: Endogenous COS-7 microscopy shows diffuse cytosolic Drp1 as well as mitochondrial puncta. Separate bovine-brain fractionation places most Drp1 in the soluble fraction; neither assay is endogenous human localization. Independent human HPA and targeted recruitment evidence support cytosol as a core recruitment pool. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-351948 | ACCEPT | Reason: The exact Reactome input entity 351943 is human DNM1L residues 1β736 in cytosol, recruited to the mitochondrial outer membrane in R-HSA-351948. The compartment is directly encoded by the target entity; it is not inferred from a neighbouring participant. |
| GO:0005874 microtubule | IBA GO_REF:0000033 | KEEP AS NON CORE | Reason: The literal microtubule IBD at PTN000170013 is on the target lineage; the transfer is not invalid because its donors are other dynamin-family members. Independent human Jurkat experiments in PMID:23798729 show endogenous Drp1 microtubule co-pelleting and colocalization, whereas endogenous HeLa Drp1 behaves differently. Rat splice constructs in human HeLa cells provide additional isoform-dependent evidence. Retain a contextual microtubule pool without claiming a universal product property. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000170013 SUPPORTS TRANSFER The literal GO:0005874 IBD is present at this node on the authenticated O00429 lineage in PTHR11566. The 736-residue target matches the family MSA exactly. The inherited function is retained; contextual evidence does not imply loss of the ancestral function. Supporting Evidence: |
| GO:0005874 microtubule | IDA PMID:9472031 A novel dynamin-like protein associates with cytoplasmic ves... | KEEP AS NON CORE | Reason: The actual original places rat DLP1-positive vesicular structures along microtubules and tests their relationship to the microtubule array. This supports the reported contextual association, not a purified human microtubule-affinity measurement. Independent endogenous human Jurkat evidence corroborates that DNM1L can occupy a microtubule-associated pool. Supporting Evidence: PMID:9472031 a large portion of DLP1-positive vesicles coincided with microtubules |
| GO:0005903 brush border | IEA GO_REF:0000107 | UNDECIDED | Reason: The literal mouse donor Q8K1M6 has a direct brush-border annotation from PMID:22114352. The original describes mouse intestinal brush-border isolation and proteomics, but the target-specific supplemental protein listing was not recovered. The old assertion that this must be contamination or functionally irrelevant is unsupported; compartment annotations do not require a distinct brush-border function. Preserve the positive donor evidence while leaving the target-specific experiment and human transfer unresolved. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8K1M6 UNRESOLVED The exact mouse IDA is PMID:22114352. Its brush-border methods were read, but the supplemental Dnm1l target row and human transfer remain unresolved. Supporting Evidence: |
| GO:0005905 clathrin-coated pit | IEA GO_REF:0000044 | KEEP AS NON CORE | Reason: The UniProt mapping explicitly derives this pool from rat O35303. In PMID:23792689, stimulated rat hippocampal neurons show Drp1 immunogold at clathrin-coated pits, and target-specific antibody controls distinguish Drp1 from classical dynamin. Retain this ortholog-grounded neuronal pool without presenting the rat assay as direct human localization or adding a human endocytosis process assertion. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0069 SUPPORTS TRANSFER Official clathrin-coated-pit mapping explicitly uses rat O35303; PMID:23792689 provides rat-neuron immunogold evidence. Supporting Evidence: |
| GO:0007005 mitochondrion organization | IMP PMID:11514614 Dynamin-related protein Drp1 is required for mitochondrial d... | MODIFY | Reason: The original human Drp1 transgene experiments in COS-7 cells resolve mitochondrial organization into Drp1-dependent division. Mitochondrial membrane fission is a supported typed descendant and describes the performed mechanical step. The separately supported intracellular distribution of mitochondria is retained in its own annotation; the checked ontology does not place that term under mitochondrial organization, so it is not used as a replacement here. Proposed replacements: mitochondrial membrane fission Supporting Evidence: |
| GO:0007005 mitochondrion organization | IMP PMID:21149567 Mff is an essential factor for mitochondrial recruitment of ... | MODIFY | Reason: The Mff study tests Drp1 recruitment and the fragmentation/elongation outcome of mitochondrial division in human HeLa cells and separate mouse knockout fibroblasts. Mitochondrial membrane fission describes the specific DNM1L work underlying the broader organization term. Proposed replacements: mitochondrial membrane fission Supporting Evidence: |
| GO:0007029 endoplasmic reticulum organization | IMP NOT PMID:11514614 Dynamin-related protein Drp1 is required for mitochondrial d... | ACCEPT | Reason: This is a NOT annotation. In the actual source, COS-7 cells expressing human Drp1(T59A) retained wild-type ER morphology and staining with protein disulfide isomerase and an ER-retained VSV-G marker. Retain the tested negative organization result; it does not assert absence of every ER-contact function or negate separate condition-dependent ER localization. Supporting Evidence: PMID:11514614 also showed ER that looked wild type |
| GO:0008017 microtubule binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Reason: The microtubule-binding IBD at PTN000170013 is literally present on the authenticated target lineage. The fly dynamin donor has experimentally grounded microtubule association in the isolated MMAP fraction and Table 1 of PMID:11076973. More directly, endogenous human Jurkat Drp1 co-pellets with microtubules and colocalizes with them in PMID:23798729. These findings justify contextual binding, while rat splice-construct results and lack of endogenous HeLa association limit universal isoform claims; no purified human affinity constant is asserted. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000170013 SUPPORTS TRANSFER The literal GO:0008017 IBD is present at this node on the authenticated O00429 lineage in PTHR11566. The 736-residue target matches the family MSA exactly. The inherited function is retained; contextual evidence does not imply loss of the ancestral function. |
| GO:0010821 regulation of mitochondrion organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Reason: The exact mouse donor is grounded in the Python C452F study, which directly measures altered mitochondrial morphology in neonatal fibroblasts and disturbed Dnm1l intramolecular interactions. Retain this regulatory consequence of the fission machinery as non-core rather than calling it direct mitochondrial transport or replacing a regulation term across branches with fission. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8K1M6 SUPPORTS TRANSFER Mouse Python C452F organelle-morphology experiments support the contextual organization claim. Supporting Evidence: |
| GO:0012505 endomembrane system | EXP PMID:11514614 Dynamin-related protein Drp1 is required for mitochondrial d... | UNDECIDED | Reason: The complete inspected source supports mitochondrial and cytosolic Drp1 while explicitly finding no ER-marker colocalization and arguing against other membrane-bound organelles under its conditions. Mitochondria are not a specific endomembrane-system descendant. Other sources support ER/Golgi and neuronal endocytic pools, but they do not establish how this paper grounds the imported broad assertion; retain it as unresolved rather than silently substituting mitochondrial outer membrane. |
| GO:0012505 endomembrane system | EXP PMID:9348079 Identification and subcellular localization of a novel mamma... | UNDECIDED | Reason: The actual abstract describes a perinuclear human DVLP pattern not superimposable on the tested Golgi, ER, endosomal or lysosomal markers. The full original and the basis for this broad curated endomembrane assertion were not recovered. Positive ER/Golgi findings from other papers are retained separately and do not erase this source-specific uncertainty. |
| GO:0012505 endomembrane system | EXP PMID:9472031 A novel dynamin-like protein associates with cytoplasmic ves... | MODIFY | Reason: The actual rat DLP1 source includes ER-marker alignment and rat liver immunogold/fractionation. ER membrane is the supported specific endomembrane location in this experiment. Preserve the rat assay scope and the later human-cell negative ER result as separate observations. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: |
| GO:0012505 endomembrane system | EXP PMID:9570752 Identification and functional characterization of a novel hu... | MODIFY | Reason: The actual abstract reports human Drp1 expressed in CHO cells in an ER-marker- and Golgi-marker-labelled perinuclear region. Refine the broad endomembrane term to ER membrane and Golgi apparatus using that source plus independent ER-membrane evidence; full original CHO assay controls remain unavailable and neither pool is asserted to be universal. Proposed replacements: endoplasmic reticulum membrane Golgi apparatus |
| GO:0012505 endomembrane system | IEA GO_REF:0000044 | MODIFY | Reason: The official broad endomembrane mapping combines early ER/Golgi studies with other membrane pools. Current ontology distinguishes this system from mitochondria. Resolve it to supported ER membrane, Golgi apparatus, clathrin-coated pit and synaptic vesicle membrane, preserving the rat neuronal evidence for the latter two and the condition-dependent ER/Golgi observations. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB-SubCell:SL-0147 SUPPORTS TRANSFER Broad endomembrane mapping is refined only to supported typed descendants with source-specific ER, Golgi, coated-pit and vesicle evidence. Proposed replacements: endoplasmic reticulum membrane Golgi apparatus clathrin-coated pit synaptic vesicle membrane |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MODIFY | Reason: The source is a human YTS membrane-proteome experiment that includes transiently associated proteins; the target-specific table/fraction assignment was not independently recovered. The broad membrane claim is independently sound. Refine using directly established mitochondrial and peroxisomal membrane pools plus contextual ER and neuronal synaptic-vesicle membrane pools, without pretending the YTS experiment identified all those compartments or proving an integral topology. Proposed replacements: mitochondrial outer membrane peroxisomal membrane endoplasmic reticulum membrane synaptic vesicle membrane |
| GO:0016020 membrane | IBA GO_REF:0000033 | MODIFY | Reason: The literal membrane IBD at PTN000170013 is on the authenticated DNM1L path and is grounded by descendant experiments. The target retains membrane association; refine to the independently supported mitochondrial outer membrane, peroxisomal membrane, contextual ER membrane and ortholog-grounded synaptic vesicle membrane. The source-specific organism and recruitment limits remain explicit, and no integral-membrane topology is inferred. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000170013 SUPPORTS TRANSFER The literal GO:0016020 IBD is present at this node on the authenticated O00429 lineage in PTHR11566. The 736-residue target matches the family MSA exactly. Target-specific evidence supplies a finer scope without rejecting the inherited function. Proposed replacements: mitochondrial outer membrane peroxisomal membrane endoplasmic reticulum membrane synaptic vesicle membrane |
| GO:0016559 peroxisome fission | IBA GO_REF:0000033 | ACCEPT | Reason: The exact peroxisome-fission IBD at PTN008520527 is on the authenticated target lineage, and direct human DLP1 division experiments independently ground the function. DNM1L performs membrane-remodelling work in the division machinery; the term is not inferred solely from a general organelle phenotype. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008520527 SUPPORTS TRANSFER The literal GO:0016559 IBD is present at this node on the authenticated O00429 lineage in PTHR11566. The 736-residue target matches the family MSA exactly. The inherited function is retained; contextual evidence does not imply loss of the ancestral function. |
| GO:0016559 peroxisome fission | IDA PMID:12618434 The dynamin-like GTPase DLP1 is essential for peroxisome div... | ACCEPT | Reason: The source reports a requirement for DLP1 in human peroxisomal division using perturbation and membrane-localization experiments. Division is separated from elongation, and PEX11B-associated recruitment is not treated as proof of direct purified DLP1βPEX11B binding. Supporting Evidence: |
| GO:0016559 peroxisome fission | IEA GO_REF:0000107 | ACCEPT | Reason: The exact mouse ortholog has direct peroxisomal-division evidence, including knockout/rescue experiments with mouse Drp1 splice products. Independent human experiments establish the same division function. Natural mouse and human splice products are not assumed equivalent merely from their names. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8K1M6 SUPPORTS TRANSFER Mouse isoform-rescue experiments in PMID:29853636 support peroxisome fission, independently demonstrated for human DNM1L. |
| GO:0016559 peroxisome fission | IMP PMID:18353969 The novel tail-anchored membrane protein Mff controls mitoch... | ACCEPT | Reason: The complete source abstract explicitly reports that Mff is required for mitochondrial and peroxisomal fission and places this in the Drp1 division machinery. Detailed original assays were not recovered; independent direct human DLP1 experiments substantiate the positive curator assertion without assigning Mff receptor activity to DNM1L. |
| GO:0016559 peroxisome fission | IMP PMID:23921378 Adaptor proteins MiD49 and MiD51 can act independently of Mf... | ACCEPT | Reason: The source shows that mitochondrial sequestration of available Drp1 can inhibit peroxisomal division, with engineered targeting experiments probing recruitment. Together with direct human peroxisomal DLP1 experiments, this supports DNM1L participation in peroxisome fission without treating the engineered constructs as natural peroxisome-specific products. |
| GO:0030672 synaptic vesicle membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Reason: The literal UniProt location is transferred from rat O35303. The original rat hippocampal study detects Drp1 in a synaptic-vesicle fraction and at neuronal endocytic structures, with antibody specificity controls, knockdown and rescue. Retain this contextual membrane pool while distinguishing it from direct human localization and from a claim that DNM1L is a constitutive structural synaptic-vesicle protein. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0260 SUPPORTS TRANSFER Official synaptic-vesicle-membrane mapping explicitly uses rat O35303; PMID:23792689 assays rat neuronal vesicles. Supporting Evidence: |
| GO:0030742 GTP-dependent protein binding | IDA PMID:25767741 Interaction with the effector dynamin-related protein 1 (Drp... | KEEP AS NON CORE | Summary: Preferential association with active Rab32 supports GTP-dependent binding. Reason: GO:0030742 covers an interaction when either partner is GTP bound. The original compares active and inactive Rab32 constructs and finds stronger association of Drp1 with the active form, with weaker analogous Rab29/Rab38 effects. This supports the binding term even though it does not establish Drp1 as a Rab GTPase activator. The cross-linked cellular association is not a purified affinity measurement. Supporting Evidence: |
| GO:0031267 small GTPase binding | IDA PMID:25767741 Interaction with the effector dynamin-related protein 1 (Drp... | KEEP AS NON CORE | Summary: Rab32-family association supports small GTPase binding. Reason: The original reports Drp1 association with Rab32, Rab29 and Rab38 and tests nucleotide-state preference. These are small monomeric GTPases, so the binding assertion is supported as a regulatory context distinct from Drp1's membrane-fission motor chemistry. The paper does not demonstrate that Drp1 accelerates Rab GTP hydrolysis. Supporting Evidence: |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:16874301 A novel mitochondrial ubiquitin ligase plays a critical role... | KEEP AS NON CORE | Summary: Drp1 associates with the MARCHF5/MITOL ubiquitin ligase. Reason: The source reports cotransfection and pulse-chase evidence that Drp1 associates with and is ubiquitinated by MITOL. This supports ubiquitin-protein-ligase binding in a regulated substrate context and does not mean that Drp1 itself is a ligase. The cached discussion is explicit, while its missing Results/Methods are not claimed as independently inspected. Keep this contextual binding function as non-core. Supporting Evidence: PMID:16874301 Cotransfection and pulseβchase experiments indicated that hFis1 and Drp1 were associated with and ubiquitinated by MITOL. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:19407830 MAPL is a new mitochondrial SUMO E3 ligase that regulates mi... | KEEP AS NON CORE | Summary: Drp1 associates with the dual ubiquitin/SUMO ligase MUL1/MAPL. Reason: The actual original detects endogenous MAPL-associated Drp1 and uses immunopurified human Drp1 as a substrate in a recombinant MAPL SUMOylation assay. MAPL also shows ubiquitin-ligase activity at higher in vitro concentrations, but the Drp1 assay chiefly addresses SUMO conjugation. The partner remains an E3 protein, so the binding class is defensible; no Drp1 ubiquitin-ligase activity or exclusively ubiquitination-mediated mechanism is implied. Supporting Evidence: |
| GO:0032991 protein-containing complex | IDA PMID:17408615 Fis1, DLP1, and Pex11p coordinately regulate peroxisome morp... | KEEP AS NON CORE | Reason: The source describes cross-linked complexes containing DLP1, Fis1 and PEX11 proteins during organelle division. This supports complex association, but does not establish a permanently stoichiometric named complex or purified ternary binding among every component. The integrated motor role is more informative than generic complex membership. Supporting Evidence: PMID:17408615 ternary complexes comprising Fis1, Pex11pbeta, and DLP1 were detected by chemical cross-linking |
| GO:0032991 protein-containing complex | IDA PMID:18353969 The novel tail-anchored membrane protein Mff controls mitoch... | KEEP AS NON CORE | Reason: The Mff study supports Drp1 participation in the division apparatus, with membrane-associated complexes discussed in the available source abstract. Complete target-specific complex-isolation Methods were not recovered. Retain contextual complex membership with curator deference, without assigning the reported Mff/Fis1 complex masses automatically to a stable DNM1L-containing assembly. Supporting Evidence: |
| GO:0042802 identical protein binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: The current ARBA00027930 branch matches the recorded dynamin-family FunFam signatures and taxon condition. Drp1 self-association is independently demonstrated and is integral to assembly of the motor, but generic identical-protein binding is not a separate core function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00027930 SUPPORTS TRANSFER Current branch 14 matches the target FunFam signatures and Eukaryota condition; target self-association is independently demonstrated. |
| GO:0042802 identical protein binding | IPI PMID:18353969 The novel tail-anchored membrane protein Mff controls mitoch... | KEEP AS NON CORE | Reason: The source-supported self-association is consistent with independent biochemical Drp1 assembly data. Complete original pair-specific Methods in this paper were not recovered, so no additional assay or affinity details are inferred. Retain the positive binding claim as a mechanism of motor assembly. |
| GO:0042802 identical protein binding | IPI PMID:21701560 Human MIEF1 recruits Drp1 to mitochondrial outer membranes a... | KEEP AS NON CORE | Reason: The actual original measures endogenous Drp1 oligomerization while testing MIEF1; the oligomerized amount is not changed by MIEF1 expression. That negative perturbation result does not negate the positive Drp1 self-association observation. Retain self-binding within the motor-assembly mechanism. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:30914652 ATAD3A oligomerization causes neurodegeneration by coupling ... | KEEP AS NON CORE | Reason: The source directly examines Drp1 oligomerization and its ATAD3A-associated regulation in the Huntington disease models. Preserve self-association as an assembly mechanism without assigning ATAD3A ATPase activity or its membrane topology to DNM1L. Supporting Evidence: |
| GO:0042803 protein homodimerization activity | IDA PMID:22265414 The mitochondrial phosphatase PGAM5 functions at the converg... | KEEP AS NON CORE | Reason: The necrosis source supports Drp1 activation and assembly in the curated experiment, but its complete original oligomerization Methods were unavailable. Independent structural/biochemical studies verify self-assembly. Retain homodimerization as an assembly feature without treating one stoichiometry as the only active motor state. |
| GO:0042803 protein homodimerization activity | IDA PMID:23530241 Interchangeable adaptors regulate mitochondrial dynamin asse... | KEEP AS NON CORE | Reason: The human Drp1 reconstitution resolves self-association and assembly of higher-order polymers. Homodimerization is a valid component of the assembly cycle, not a distinct physiological core or proof that a simple dimer alone performs scission. Supporting Evidence: |
| GO:0042803 protein homodimerization activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Reason: The exact mouse Python source uses yeast two-hybrid tests to distinguish preserved intermolecular Dnm1l association from impaired intramolecular interaction, alongside structural modelling. Retain the conserved self-association claim; the model is not a newly solved Dnm1l structure and the mutation does not establish wholesale loss of dimerization. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8K1M6 SUPPORTS TRANSFER Mouse Python study tests intermolecular self-association; its intramolecular interaction defect is a distinct result. Supporting Evidence: |
| GO:0043653 mitochondrial fragmentation involved in apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Reason: The apoptotic-fragmentation IBD at PTN002611464 is present on the authenticated DNM1L lineage with direct human evidence among its descendants. The target performs the mitochondrial remodelling step during tested apoptosis conditions. Retain this cell-death context as non-core relative to the constitutive organelle-division mechanism, without inferring that Drp1 executes every stage or every form of apoptosis. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002611464 SUPPORTS TRANSFER The literal GO:0043653 IBD is present at this node on the authenticated O00429 lineage in PTHR11566. The 736-residue target matches the family MSA exactly. The inherited function is retained; contextual evidence does not imply loss of the ancestral function. Supporting Evidence: |
| GO:0043653 mitochondrial fragmentation involved in apoptotic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: The current ARBA00087404 condition set matches the target FunFam signatures and Euarchontoglires lineage. Direct human Drp1 perturbation experiments support the apoptotic fragmentation context. Keep that context without making apoptosis an obligate outcome of Drp1 activity or interpreting the rule as a direct caspase function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00087404 SUPPORTS TRANSFER Current branch 0 matches the target signatures and Euarchontoglires lineage; apoptotic fragmentation is positive contextual evidence. Supporting Evidence: |
| GO:0043653 mitochondrial fragmentation involved in apoptotic process | IMP PMID:12499352 Spatial and temporal association of Bax with mitochondrial f... | KEEP AS NON CORE | Reason: The actual human-cell study shows mitochondrial fragmentation and Bax-associated fission sites during staurosporine-induced apoptosis. Dominant-negative Drp1 blocks fragmentation while Bax translocation can still occur. Retain the specific fragmentation context without promoting it to all apoptosis signalling or claiming that Drp1 is the apoptotic protease. Supporting Evidence: PMID:12499352 Colocalization of Bax with Drp1 at the mitochondrial foci is apparent in apoptotic cells. |
| GO:0048312 intracellular distribution of mitochondria | IBA GO_REF:0000033 | KEEP AS NON CORE | Reason: The exact distribution IBD at PTN002480309 lies on the target path and has direct human and rodent descendant grounding. Drp1-dependent division affects the spatial arrangement of the mitochondrial network. Retain that process as contextual coverage, without assigning a cargo-transport motor activity distinct from the membrane-fission motor. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002480309 SUPPORTS TRANSFER The literal GO:0048312 IBD is present at this node on the authenticated O00429 lineage in PTHR11566. The 736-residue target matches the family MSA exactly. The inherited function is retained; contextual evidence does not imply loss of the ancestral function. Supporting Evidence: |
| GO:0048312 intracellular distribution of mitochondria | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: The current ARBA00089911 branch matches the target signatures and lineage. Experiments with human Drp1 constructs in COS-7 cells support mitochondrial redistribution when Drp1-dependent division is impaired, so retain the process without claiming ATP-driven transport along cytoskeletal tracks. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00089911 SUPPORTS TRANSFER Current branch 0 matches the target signatures and Euarchontoglires lineage; distribution is retained without assigning microtubule transport activity. Supporting Evidence: |
| GO:0048312 intracellular distribution of mitochondria | IMP PMID:11514614 Dynamin-related protein Drp1 is required for mitochondrial d... | KEEP AS NON CORE | Reason: The source directly measures changes in the distribution and clustering of mitochondria after interfering with Drp1. It interprets these in the context of a division defect. The observation remains valid even though it does not establish an independent organelle-transport mechanism. Supporting Evidence: PMID:11514614 mitochondria to form perinuclear clusters |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:9472031 A novel dynamin-like protein associates with cytoplasmic ves... | KEEP AS NON CORE | Reason: The original rat DLP1 microscopy reports a perinuclear distribution associated with cytoplasmic and ER-linked structures. Retain this spatial pattern as contextual localization rather than an exclusive compartment or a human-only assay. Supporting Evidence: |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:9570752 Identification and functional characterization of a novel hu... | KEEP AS NON CORE | Reason: The actual abstract reports a perinuclear pattern after human Drp1 expression in CHO cells, including ER and Golgi marker overlap. Preserve that source-specific pattern; it is not a claim that every endogenous human-cell pool is perinuclear. Supporting Evidence: |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: The current ARBA00091589 branch matches the target signatures and taxon condition. Earlier localization studies support a perinuclear pool in their tested expression/cell contexts, but this is not an exclusive cellular location or a separate physiological function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00091589 SUPPORTS TRANSFER Current branch 15 matches the target signatures and Euarchontoglires lineage; the perinuclear pool is context dependent. |
| GO:0050714 positive regulation of protein secretion | IDA PMID:9570752 Identification and functional characterization of a novel hu... | KEEP AS NON CORE | Reason: The actual source abstract reports increased secreted luciferase with wild-type human Drp1 expression in CHO cells and reduced release with a GTP-binding-site mutant. Later work did not reproduce a general secretory-pathway effect and raised a secondary mitochondrial explanation. Preserve the measured positive regulation in its tested context rather than dismissing it as nonexistent; the full original controls remain unavailable and no universal secretion core is asserted. Supporting Evidence: PMID:9570752 the overexpression of wild-type DRP1 increases the secretion of this marker |
| GO:0051259 protein complex oligomerization | IMP PMID:27145208 A novel de novo dominant negative mutation in DNM1L impairs ... | KEEP AS NON CORE | Reason: The source directly tests self-association/oligomerization and dominant-negative effects of Drp1 variants, using mouse constructs alongside human disease evidence. Retain assembly as part of the motor mechanism without confusing the tested constructs with every natural human product or inventing a separate oligomerization core. Supporting Evidence: PMID:27145208 DRP1R403C weakly interacts with wild-type DRP1, suggesting that the R403C mutation affects DRP1 oligomerization but not to the extent of the A395D mutation |
| GO:0060047 heart contraction | IEA GO_REF:0000107 | KEEP AS NON CORE | Reason: The exact mouse donor evidence is the Python C452F study: cardiac catheterization shows impaired contraction and relaxation, and myocardial energetic abnormalities accompany organelle-dynamics defects. It is not a cardiomyocyte-specific knockout experiment. Retain the physiological phenotype with ortholog-transfer and indirect-mechanism limits; DNM1L is not thereby a sarcomeric contractile protein. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8K1M6 SUPPORTS TRANSFER Mouse Python C452F cardiac measurements support contraction consequences, not a cardiomyocyte-specific knockout or contractile enzyme. Supporting Evidence: |
| GO:0090023 positive regulation of neutrophil chemotaxis | IMP PMID:28388446 Phosphorylation of dynamin-related protein 1 at Ser616 regul... | UNDECIDED | Reason: The abstract supports MCU-dependent polarization/chemotaxis in human neutrophils and links this to Drp1 phosphorylation and mitochondrial fission. Curator notes identify a Drp1-suppression experiment in Figure 6, but the actual full figure and target-specific Methods were not recovered. The old categorical rejection as merely an indirect phenotype is not justified by this access limit. Retain the positive assertion as unresolved without claiming a direct chemotactic receptor or motility motor role. Supporting Evidence: |
| GO:0090141 positive regulation of mitochondrial fission | IEA GO_REF:0000117 | KEEP AS NON CORE | Reason: The current ARBA00087305 branch matches the target signatures and lineage. The term describes an increase in fission rate or extent and belongs to the regulation branch; it is not an ancestor of the membrane-fission process. Preserve supported regulatory context as non-core rather than replacing it across branches solely because Drp1 also performs scission. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00087305 SUPPORTS TRANSFER Current branch 1 matches the target signatures and Euarchontoglires lineage; positive fission regulation is kept separate from the direct fission branch. |
| GO:0090141 positive regulation of mitochondrial fission | IMP PMID:19279012 Loss of PINK1 function promotes mitophagy through effects on... | KEEP AS NON CORE | Reason: In human SH-SY5Y PINK1-deficient cells, dominant-negative Drp1 reduces mitochondrial fragmentation and the associated mitophagy response. The actual indexed Results and Figure 7 support this contextual positive-control relationship. Retain the regulation term without claiming that Drp1 is a PINK1 kinase or replacing a regulation assertion across branches by its direct scission activity. Supporting Evidence: PMID:19279012 The dominant negative Drp1 mutant inhibited both fission and mitophagy in PINK1-deficient cells. |
| GO:0090141 positive regulation of mitochondrial fission | TAS PMID:20436456 The BH3-only Bnip3 binds to the dynamin Opa1 to promote mito... | KEEP AS NON CORE | Reason: The actual indexed original shows that Bnip3-associated fragmentation in HeLa cells is reduced by dominant-negative Drp1K38A while Bnip3 inhibits Opa1-dependent fusion. Thus the target is experimentally involved despite the abstract foregrounding Bnip3/Opa1. Retain the contextual positive fission regulation without assigning Bnip3βOpa1 binding or fusion inhibition to Drp1. Supporting Evidence: |
| GO:0090149 mitochondrial membrane fission | IDA PMID:11514614 Dynamin-related protein Drp1 is required for mitochondrial d... | ACCEPT | Reason: The source tests human Drp1 constructs in COS-7 and C2C12 cells, with endogenous COS-7 microscopy and bovine-brain fractionation assessed separately. The transgene experiments support division and puncta at division sites; later purified human reconstitution confirms the membrane-scission interpretation. The older study is not an endogenous human-cell assay or a purified severing experiment. |
| GO:0090149 mitochondrial membrane fission | IMP PMID:21822277 RALA and RALBP1 regulate mitochondrial fission at mitosis. | ACCEPT | Reason: The source tests mitotic Drp1 recruitment and fragmentation through the RALA/RALBP1 pathway. Drp1 performs the membrane-fission step; the RALBP1-assisted kinase arrangement and Ral GTPase signalling are separate upstream mechanisms. Supporting Evidence: PMID:21822277 mitochondria in RalA or RalBP1 knockdown cells did not undergo fragmentation, but instead maintained a netlike appearance throughout mitosis |
| GO:0090149 mitochondrial membrane fission | IMP PMID:27301544 DNM1L-related encephalopathy in infancy with Leigh syndrome-... | UNDECIDED | Reason: This imported experimental source could not be assessed beyond its cached bibliographic record; the substantive abstract/full text and original target assays were unavailable. The membrane-fission function is independently certain, but that does not authenticate this particular experiment. Preserve the original curator assertion pending source-specific access. |
| GO:0090149 mitochondrial membrane fission | IMP PMID:27328748 Biallelic Mutations in DNM1L are Associated with a Slowly Pr... | ACCEPT | Reason: Human patient fibroblasts show a defect in mitochondrial division that is rescued by wild-type DNM1L. The paper separately tests a corresponding yeast mutation; those species-specific experiments are not conflated. The positive human result supports mitochondrial membrane fission, while complete supplementary Methods were not inspected. Supporting Evidence: |
| GO:0099073 mitochondrion-derived vesicle | IDA PMID:26618722 Parkinson's disease-associated mutant VPS35 causes mitochond... | KEEP AS NON CORE | Reason: The actual source identifies DLP1 in mitochondrion-derived vesicles by human M17 imaging and immuno-EM, and in a budding system using mouse liver mitochondria plus M17 cytosol. It explicitly interprets DLP1 as vesicle cargo during turnover of mitochondrial assemblies. A component annotation is compatible with cargo presence; it does not assert that DNM1L catalyses production of these vesicles or lysosomal degradation. Supporting Evidence: PMID:26618722 revealed the presence of DLP1-positive immunogold particles in these MDVs |
| GO:1900063 regulation of peroxisome organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Reason: The exact mouse Python donor study documents elongated peroxisomes in neonatal fibroblasts bearing C452F Dnm1l. Retain regulation of peroxisome organization as a contextual consequence of the division machinery, without claiming a distinct PEX11-like elongation activity or replacing the regulation branch mechanically with fission. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8K1M6 SUPPORTS TRANSFER Mouse Python C452F neonatal-fibroblast peroxisome elongation grounds the contextual organization claim. Supporting Evidence: |
| GO:1901524 regulation of mitophagy | IGI PMID:19279012 Loss of PINK1 function promotes mitophagy through effects on... | KEEP AS NON CORE | Reason: The actual indexed PINK1-deficient human SH-SY5Y study shows that dominant-negative Drp1 reduces the mitophagy response together with fragmentation. This supports a contextual regulatory contribution to mitochondrial turnover. It does not establish a DNM1L autophagy-receptor activity or universal dependence of all mitophagy on Drp1. Supporting Evidence: |
| GO:1903532 positive regulation of secretion by cell | IEA GO_REF:0000117 | MODIFY | Reason: The current ARBA00089016 branch matches the target signatures and lineage. The specific positive experimental observation is secretion of a protein reporter in the historical CHO assay, so positive regulation of protein secretion is the supported descendant. Later negative results limit generalization but do not erase the earlier measured response; a constitutive secretion core is not asserted. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: ARBA:ARBA00089016 SUPPORTS TRANSFER Current branch 8 matches the target signatures and Euarchontoglires lineage; the measured protein-reporter response supplies the narrower secretion term. Proposed replacements: positive regulation of protein secretion |
| GO:1903578 regulation of ATP metabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Reason: The exact mouse donor is grounded in the Python C452F study, which measured an approximately halved myocardial ATP/adenine-nucleotide pool by HPLC and independent assays, while brain and liver were unaffected at the tested age. Retain a tissue-context regulatory consequence of mitochondrial dynamics. This is not ATP synthesis by DNM1L, and the source is not the separate circadian-phosphorylation study cited in the older rationale. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8K1M6 SUPPORTS TRANSFER Mouse Python C452F myocardial ATP measurements ground this term; no ATP-synthesis activity is transferred. Supporting Evidence: |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Which physiological DNM1L products occupy microtubule, neuronal-vesicle and organelle-membrane pools, and which localization differences reflect alternative splicing rather than expression level or cell type?
Q: How do membrane adaptors and lipid composition couple Drp1 GTP hydrolysis to complete scission in cells, including coordination of mitochondrial inner and outer membranes?
Q: What source-specific DNM1L experiments support the three imported PMID37971521 assertions, and how do they relate to the independently verified PMID38587461 study?
Q: Does the mouse brush-border proteomic observation reflect a conserved human DNM1L pool, and can the original target-specific supplemental record be recovered?
Experiment: Compare sequence-authenticated natural human DNM1L products at matched endogenous expression using compartment-resolved imaging and orthogonal fractionation, including mitochondrial/peroxisomal membranes and microtubule or neuronal vesicle pools.
Experiment: Combine purified Drp1 and defined organelle adaptors/lipids with time-resolved membrane-scission measurements, then test matched hydrolysis and assembly mutants in cellular rescue experiments.
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)