CHMP2B is a human ESCRT-III protein that assembles into membrane-associated polymers and contributes to endosomal sorting, cytokinetic abscission, nuclear-envelope reassembly and membrane repair. Its N-terminal membrane-interacting region and polymer-forming core support membrane deformation, while a C-terminal MIT-interacting motif recruits VPS4 ATPases for dynamic remodeling and recycling. The protein has a diffuse cytosolic pool and is transiently recruited to membranes; it is not itself an ATPase. Its functions can overlap with those of CHMP2A, with the extent of redundancy depending on the cellular process. Disease-associated C-terminal variants can alter assembly turnover, endolysosomal delivery and nuclear export, producing toxic effects that need not represent simple loss of every wild-type function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005771 multivesicular body | IBA GO_REF:0000033 | ACCEPT | Summary: CHMP2B acts at multivesicular bodies. Reason: Retain the conserved endosomal ESCRT role. The current projection specifies is_active_in, rather than permanent residence. Target membrane remodeling and endosomal phenotypes independently support the compartment; the historical PAINT node placement was not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000049603 UNRESOLVED Current PTN and descendant evidence are authentic; the historical PAINT ancestral placement/alignment was not reconstructed. Independent target evidence supports the retained biology. Donor count and target self-reference are not failure criteria. |
| GO:0015031 protein transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain broad protein transport at endosomal sorting scope. Reason: The phylogenetic annotation is compatible with ESCRT-mediated sorting and degradation of membrane cargo. It does not mean that CHMP2B is a motor or a general soluble cargo carrier. Current donors and the actual PTN are recorded separately without rewriting the historical assertion. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000049603 UNRESOLVED Current PTN and descendant evidence are authentic; the historical PAINT ancestral placement/alignment was not reconstructed. Independent target evidence supports the retained biology. Donor count and target self-reference are not failure criteria. |
| GO:0032509 endosome transport via multivesicular body sorting pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Retain endosomal transport through the MVB pathway. Reason: This is the established conserved ESCRT sorting role, supported by target ESCRT assembly and endosomal cargo-trafficking defects. The protein contributes membrane-remodeling structure; it is not assigned ATPase or cargo protease activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000049603 UNRESOLVED Current PTN and descendant evidence are authentic; the historical PAINT ancestral placement/alignment was not reconstructed. Independent target evidence supports the retained biology. Donor count and target self-reference are not failure criteria. |
| GO:0045324 late endosome to vacuole transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the conserved late-endosome-to-vacuole pathway role. Reason: The PAINT inference spans the conserved endosomal pathway, including yeast/fungal vacuolar contexts. Human CHMP2B contributes endolysosomal trafficking; this broad pathway assertion does not establish an intrinsic membrane-fusion activity. The historical ancestral judgment remains unreconstructed. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000049603 UNRESOLVED Current PTN and descendant evidence are authentic; the historical PAINT ancestral placement/alignment was not reconstructed. Independent target evidence supports the retained biology. Donor count and target self-reference are not failure criteria. |
| GO:0000815 ESCRT III complex | IBA GO_REF:0000033 | ACCEPT | Summary: CHMP2B is an ESCRT-III subunit. Reason: Endogenous human CHMP2B is immunogold-labeled on membrane-associated ESCRT-III spirals, and defined human CHMP2B constructs assemble membrane-deforming polymers. These target experiments support membership independently of the unreconstructed historical PAINT node. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000049603 UNRESOLVED Current PTN and descendant evidence are authentic; the historical PAINT ancestral placement/alignment was not reconstructed. Independent target evidence supports the retained biology. Donor count and target self-reference are not failure criteria. |
| GO:0000776 kinetochore | IEA GO_REF:0000117 | UNDECIDED | Summary: The exact kinetochore localization remains unresolved. Reason: The current ARBA rule output is authentic, but the target-specific localization basis has not been resolved. Accessible original PMID:26040712 panels explicitly identify CHMP4B at kinetochores/microtubules and CHMP2A in another panel; the unavailable main body prevents excluding additional CHMP2B experiments. No misattribution or target absence is asserted. |
| GO:0001778 plasma membrane repair | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP2B contributes to plasma-membrane repair. Reason: Retain the electronic process with independent target evidence. Human CAL51 live imaging and pore-forming-toxin pulse/chase assays place CHMP2B after initial annexin-mediated sealing and in later restoration of membrane integrity. This is a contextual ESCRT remodeling contribution, not evidence that CHMP2B alone closes every wound. |
| GO:0005643 nuclear pore | IEA GO_REF:0000117 | MODIFY | Summary: Refine the location to the nuclear envelope. Reason: GO:0005643 denotes the nuclear pore complex. Full PMID:26040713 Figures 1A/1B and Extended Data Figure 1A directly localize endogenous human CHMP2B to the reforming nuclear envelope; the separate CHMP2A ultrastructural analysis distinguishes non-NPC membrane openings. The broader envelope location is positively supported, while the original NPC incorporation basis remains unresolved. The historical source is unchanged; this recommendation does not manufacture a new relation or disprove another NPC-associated pool. Proposed replacements: nuclear envelope |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000117 | UNDECIDED | Summary: The precise autophagic/lysosomal membrane location is unresolved. Reason: The original electronic mapping is preserved. Full PMID:17984323 demonstrates mutant CHMP2B effects on autophagic clearance, but its inspected immuno-EM labels p62 rather than directly localizing endogenous CHMP2B to this membrane. General ESCRT function and cargo accumulation do not settle this compartment-specific assertion. No absence of a transient target pool is inferred. |
| GO:0005828 kinetochore microtubule | IEA GO_REF:0000117 | UNDECIDED | Summary: The exact kinetochore localization remains unresolved. Reason: The current ARBA rule output is authentic, but the target-specific localization basis has not been resolved. Accessible original PMID:26040712 panels explicitly identify CHMP4B at kinetochores/microtubules and CHMP2A in another panel; the unavailable main body prevents excluding additional CHMP2B experiments. No misattribution or target absence is asserted. |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: Retain the soluble cytosolic pool. Reason: The original UniProt subcellular-location mapping agrees with diffuse endogenous CHMP2B staining and low-expression/endogenous-tag human-cell imaging. Recruitment to membranes is transient and does not negate a cytosolic pool. |
| GO:0007034 vacuolar transport | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Retain broad vacuolar transport at conserved ESCRT scope. Reason: IPR005024 is the authentic Snf7-family mapping. Conserved endosomal sorting supports this broad term, but it is not a separate transport mechanism or an ATP-driven motor activity of CHMP2B. |
| GO:0007080 mitotic metaphase chromosome alignment | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain chromosome-alignment phenotype as contextual. Reason: Human-cell siRNA experiments in PMID:20616062 measured chromosome misalignment and nuclear fragmentation after CHMP2B depletion. They support the existing process assertion without establishing direct kinetochore binding or a separate chromosome motor mechanism. |
| GO:0015031 protein transport | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Retain the historical broad transport assertion. Reason: The archived keyword-derived source object is retained even though this exact tuple is absent from the fresh normal projection. Endosomal cargo trafficking supports the broad biological claim. Its retention is historical provenance, not evidence of an additional current source or a molecular motor. |
| GO:0030496 midbody | IEA GO_REF:0000117 | ACCEPT | Summary: Retain CHMP2B localization at the midbody. Reason: Direct endogenous human CHMP2B immunofluorescence in PMID:26040713 supports this compartment. The ARBA assertion is not used to infer that every ESCRT subunit has an identical recruitment time or requirement. |
| GO:0031468 nuclear membrane reassembly | IEA GO_REF:0000117 | ACCEPT | Summary: Retain a cooperative nuclear-envelope reassembly role. Reason: Full human HeLa experiments demonstrate CHMP2B recruitment and a cooperative contribution with CHMP2A. CHMP2B single depletion has little effect on sealing under the tested conditions, whereas combined depletion has a stronger phenotype; this does not make CHMP2B independently essential in every setting. |
| GO:0031902 late endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Retain the endosomal membrane compartment. Reason: The original localization mapping is consistent with the conserved ESCRT-III endosomal role, transient membrane recruitment, and human CHMP2B-associated endosomal phenotypes. Constitutive high occupancy of all endosomes is not implied; most endogenous protein is diffuse at steady state. |
| GO:0032585 multivesicular body membrane | IEA GO_REF:0000117 | ACCEPT | Summary: Retain the endosomal membrane compartment. Reason: The original localization mapping is consistent with the conserved ESCRT-III endosomal role, transient membrane recruitment, and human CHMP2B-associated endosomal phenotypes. Constitutive high occupancy of all endosomes is not implied; most endogenous protein is diffuse at steady state. |
| GO:0039702 viral budding via host ESCRT complex | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain viral budding as a contextual use of ESCRT machinery. Reason: Human CHMP2B contributes redundantly with CHMP2A during HIV-1 budding. Pairwise depletion and infectivity/release experiments support viral use of the host remodeling apparatus, without making viral propagation the defining cellular function or transferring another CHMP paralog structure to CHMP2B. |
| GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain degradation through the MVB sorting pathway. Reason: The annotation describes a pathway-level contribution to delivery and clearance of ubiquitinated membrane cargo. CHMP2B is a structural ESCRT participant rather than a protease, deubiquitinase, or ubiquitin-transfer enzyme. Mutant clearance defects must not be read as a purified catalytic assay. |
| GO:0046761 viral budding from plasma membrane | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain viral budding as a contextual use of ESCRT machinery. Reason: Human CHMP2B contributes redundantly with CHMP2A during HIV-1 budding. Pairwise depletion and infectivity/release experiments support viral use of the host remodeling apparatus, without making viral propagation the defining cellular function or transferring another CHMP paralog structure to CHMP2B. |
| GO:0061952 midbody abscission | IEA GO_REF:0000117 | ACCEPT | Summary: Retain the cytokinetic abscission role. Reason: Human CHMP2B depletion causes cytokinesis defects in the ESCRT survey, and direct midbody localization plus membrane-remodeling ability support performed structural work. This is not a claim that the isolated protein autonomously severs a midbody. |
| GO:0071985 multivesicular body sorting pathway | IEA GO_REF:0000117 | ACCEPT | Summary: Retain the MVB sorting role. Reason: The electronic pathway assertion agrees with the conserved ESCRT-III membrane-remodeling function and target endosomal cargo-trafficking evidence. Individual disease mutants can impair endosome-lysosome fusion while leaving intraluminal cargo sorting intact, so mutant phenotypes do not define a universal block of every MVB step. |
| GO:0097352 autophagosome maturation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain autophagosome maturation as a contextual pathway role. Reason: Full PMID:17984323 measures increased autophagic structures and defective aggregate clearance with disease-associated CHMP2B truncations. This supports the existing pathway connection but does not isolate CHMP2B-mediated phagophore closure, autophagosome initiation, or an intrinsic fusion activity. |
| GO:1901673 regulation of mitotic spindle assembly | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain regulation of spindle assembly at phenotype scope. Reason: Human CHMP2B depletion produces multipolar spindle and centrosome-number phenotypes in PMID:20616062. The responsible step remains unresolved; the paper does not establish CHMP2B as a microtubule motor or a direct spindle-building factor. |
| GO:1902774 late endosome to lysosome transport | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain late-endosomal delivery to lysosomes. Reason: CHMP2B-dependent endosomal homeostasis and mutant-associated defects in lysosomal delivery support this existing pathway assertion. The evidence does not distinguish an autonomous fusion activity from persistent ESCRT assembly and impaired access of downstream fusion machinery. |
| GO:1904930 amphisome membrane | IEA GO_REF:0000117 | UNDECIDED | Summary: The precise autophagic/lysosomal membrane location is unresolved. Reason: The original electronic mapping is preserved. Full PMID:17984323 demonstrates mutant CHMP2B effects on autophagic clearance, but its inspected immuno-EM labels p62 rather than directly localizing endogenous CHMP2B to this membrane. General ESCRT function and cargo accumulation do not settle this compartment-specific assertion. No absence of a transient target pool is inferred. |
| GO:0005515 protein binding | IPI PMID:16730941 A systematic analysis of human CHMP protein interactions: ad... | KEEP AS NON CORE | Summary: Retain the measured CHMP3 association. Reason: An exact curated positive yeast two-hybrid record joins human CHMP2B and CHMP3 for this PMID. It supports binding at the tested assay scope; no kinase, motor, or regulatory activity is transferred from the partner, and no more informative specific binding class was established. Retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, which preserves supported generic binding when no better evidence-backed term is established. |
| GO:0005515 protein binding | IPI PMID:21044950 Genome-wide YFP fluorescence complementation screen identifi... | KEEP AS NON CORE | Summary: Retain the target-specific RAP1 association. Reason: The BHF-UCL records resolve human TERF2IP/RAP1 Q9NYB0, not RIF1. A BiFC result in HTC75 cells and an independent tagged pull-down in HEK293T are linked to Supplementary Tables 1 and 2. These support contextual physical association, without establishing direct purified binding, telomeric DNA recognition by CHMP2B, or a physiological telomere-regulatory role. Retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, which preserves supported generic binding when no better evidence-backed term is established. |
| GO:0005515 protein binding | IPI PMID:22046132 The SARS-coronavirus-host interactome: identification of cyc... | KEEP AS NON CORE | Summary: Retain the two source-specific SARS protein associations. Reason: This historical unscoped aggregate is preserved. The current source splits nsp1 and nsp9 processed products, each with a positive pooling-Y2H record and tagged mammalian LUMIER corroboration. The separately appended current assertions retain their exact product IDs. Binding does not establish a native infection mechanism or virion binding. This retained historical aggregate duplicates the corresponding appended current scoped assertions for provenance; it is not counted as an additional current GOA assertion. Retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, which preserves supported generic binding when no better evidence-backed term is established. |
| GO:0005515 protein binding | IPI PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in... | KEEP AS NON CORE | Summary: Retain direct CHMP4B and CHMP3 binding. Reason: The historical aggregate is retained, and the two current partners are separately represented. Actual PMID:23051622 SPR experiments use full-length C-terminal His-tagged CHMP2B with defined CHMP4B/CHMP3 constructs, including negative-channel correction. This is genuine direct binding; the CHMP2A–CHMP3 cryo-EM tube is a different experiment. This retained historical aggregate duplicates the corresponding appended current scoped assertions for provenance; it is not counted as an additional current GOA assertion. Retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, which preserves supported generic binding when no better evidence-backed term is established. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: Retain the measured CHMP4B complex association. Reason: The exact target pair is present in a tagged co-immunoprecipitation physical-association record. This provides positive complex-context evidence but not a purified binary interface or an independently established CHMP2B enzymatic activity. Retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, which preserves supported generic binding when no better evidence-backed term is established. |
| GO:0000421 autophagosome membrane | IDA PMID:17984323 Functional multivesicular bodies are required for autophagic... | UNDECIDED | Summary: The compartment-specific target localization is unresolved. Reason: The full original main article was read. Its CHMP2B truncation experiments show defective clearance and altered LC3/p62 structures; the inspected ultrastructural membrane labels are p62, not a target-specific CHMP2B localization assay. The accessible supplemental description does not resolve endogenous CHMP2B on this exact membrane. Preserve the curator assertion without claiming a wrong-gene error or excluding transient association. |
| GO:0000776 kinetochore | IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly... | UNDECIDED | Summary: The exact CHMP2B kinetochore signal remains unresolved. Reason: Accessible PMID:26040712 Extended Data panels explicitly identify CHMP4B for kinetochore/microtubule signals and CHMP2A in another panel. The complete original main Methods/Results remain inaccessible, so this is not proof of misattribution or absence of a separate CHMP2B experiment. The original experimental assertion remains intact. |
| GO:0001778 plasma membrane repair | IDA PMID:24482116 ESCRT machinery is required for plasma membrane repair | ACCEPT | Summary: Retain a direct contribution to membrane repair. Reason: The original PMID:24482116 source remains intact and access is limited to its abstract/available summary. Independent full PMID:42349418 directly tracks endogenous-tagged and low-expression human CHMP2B at injuries and measures later recovery after toxin exposure. It supports the function while distinguishing initial annexin sealing from later ESCRT-mediated restoration. |
| GO:0005765 lysosomal membrane | IDA PMID:17984323 Functional multivesicular bodies are required for autophagic... | UNDECIDED | Summary: The compartment-specific target localization is unresolved. Reason: The full original main article was read. Its CHMP2B truncation experiments show defective clearance and altered LC3/p62 structures; the inspected ultrastructural membrane labels are p62, not a target-specific CHMP2B localization assay. The accessible supplemental description does not resolve endogenous CHMP2B on this exact membrane. Preserve the curator assertion without claiming a wrong-gene error or excluding transient association. |
| GO:0005828 kinetochore microtubule | IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly... | UNDECIDED | Summary: The exact CHMP2B kinetochore signal remains unresolved. Reason: Accessible PMID:26040712 Extended Data panels explicitly identify CHMP4B for kinetochore/microtubule signals and CHMP2A in another panel. The complete original main Methods/Results remain inaccessible, so this is not proof of misattribution or absence of a separate CHMP2B experiment. The original experimental assertion remains intact. |
| GO:0005886 plasma membrane | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: Retain plasma-membrane association. Reason: Endogenous CHMP2B immunogold labeling and unroofed-cell imaging in PMID:24878737 place the target on membrane-associated ESCRT spirals after VPS4 depletion. This is deep-etch EM, not cryo-EM, and it is a trapped-assembly condition. The current located_in and colocalizes_with assertions are separately preserved rather than merged into a stronger relation. This retained historical aggregate duplicates the corresponding appended current scoped assertions for provenance; it is not counted as an additional current GOA assertion. Supporting Evidence: |
| GO:0006914 autophagy | IMP PMID:17984323 Functional multivesicular bodies are required for autophagic... | KEEP AS NON CORE | Summary: Retain the autophagy connection with mutant scope. Reason: The source compares human WT CHMP2B with FTD-associated truncations and measures LC3/p62 accumulation and impaired clearance. It supports an existing autophagy contribution in the endolysosomal context, but does not establish a direct autophagosome-closing or catalytic function for isolated WT CHMP2B. Supporting Evidence: |
| GO:0006997 nucleus organization | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | KEEP AS NON CORE | Summary: Retain nuclear-organization phenotypes. Reason: CHMP2B depletion in the human ESCRT survey produces abnormal nuclear morphology and fragmentation. This broad organization term is supported at perturbation scope; the experiment does not identify a separate chromatin-binding activity. Supporting Evidence: |
| GO:0007080 mitotic metaphase chromosome alignment | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | KEEP AS NON CORE | Summary: Retain the chromosome-alignment phenotype. Reason: The human siRNA study observes chromosome misalignment following CHMP2B depletion. This is not a direct kinetochore-binding assay or a demonstration of motor activity. Supporting Evidence: |
| GO:0030496 midbody | IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly... | ACCEPT | Summary: Retain midbody localization with independent target corroboration. Reason: The original PMID:26040712 assertion is preserved despite incomplete main-body access. Independent full PMID:26040713 Figure 1 shows endogenous human CHMP2B at the midbody as well as reforming nuclear envelope, supporting the compartment without claiming the original target panel was recovered. |
| GO:0031468 nuclear membrane reassembly | IMP PMID:26040713 ESCRT-III controls nuclear envelope reformation | ACCEPT | Summary: Retain cooperative nuclear-envelope reassembly. Reason: Endogenous human CHMP2B is recruited to the reforming nuclear envelope. In the HeLa sealing assay, CHMP2B depletion alone has a small effect and combined CHMP2A/B depletion is stronger. The result supports cooperative ESCRT participation, not universal single-subunit essentiality or stable NPC membership. Supporting Evidence: |
| GO:0032585 multivesicular body membrane | IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but... | ACCEPT | Summary: Retain the established endosomal ESCRT membrane location. Reason: The original hVps24 study is retained without a wrong-paralog inference from its title. Its selected cache lacks complete Results/Methods and the exact CHMP2B panel was not recovered. Independent target endosomal localization and membrane-assembly evidence support the compartment; target-specific full-source attribution remains an access limit. |
| GO:0036258 multivesicular body assembly | NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a... | ACCEPT | Summary: Retain the conserved MVB assembly contribution. Reason: The original NAS source studies yeast Vta1/Vps4 recycling, not purified human CHMP2B. Conserved ESCRT assembly and independent human CHMP2B membrane-deformation evidence support the existing structural pathway role. No Vta1 ATPase-stimulation activity is transferred to CHMP2B. |
| GO:0039702 viral budding via host ESCRT complex | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | KEEP AS NON CORE | Summary: Retain viral budding at ESCRT assembly scope. Reason: The original study visualizes endogenous CHMP2B in VPS4-trapped cellular ESCRT spirals and examines Gag-associated membrane structures; not every Gag perturbation isolates CHMP2B. Independent human CHMP2B depletion experiments support HIV budding. The contextual process is retained without interpreting another paralog polymer as a CHMP2B structure. |
| GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | IDA PMID:17984323 Functional multivesicular bodies are required for autophagic... | KEEP AS NON CORE | Summary: Retain pathway participation in ubiquitinated cargo clearance. Reason: The full paper shows disrupted aggregate clearance in ESCRT-depleted cells and disease-linked CHMP2B mutants. This is a pathway contribution, not intrinsic proteolytic or ubiquitin-conjugating chemistry by CHMP2B. Supporting Evidence: |
| GO:0046761 viral budding from plasma membrane | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | KEEP AS NON CORE | Summary: Retain viral budding at ESCRT assembly scope. Reason: The original study visualizes endogenous CHMP2B in VPS4-trapped cellular ESCRT spirals and examines Gag-associated membrane structures; not every Gag perturbation isolates CHMP2B. Independent human CHMP2B depletion experiments support HIV budding. The contextual process is retained without interpreting another paralog polymer as a CHMP2B structure. |
| GO:0051469 vesicle fusion with vacuole | NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a... | UNDECIDED | Summary: The specific fusion-step assignment is unresolved. Reason: The original NAS source directly studies yeast Vta1/Vps4-dependent ESCRT recycling. Independent human CHMP2B mutant experiments impair endosome-to-lysosome delivery and show altered Rab7 access, but do not distinguish CHMP2B performing bilayer fusion from an upstream sorting/recycling contribution. The precise fusion assertion is retained unresolved rather than categorically rejected. |
| GO:0061763 multivesicular body-lysosome fusion | NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a... | UNDECIDED | Summary: The specific fusion-step assignment is unresolved. Reason: The original NAS source directly studies yeast Vta1/Vps4-dependent ESCRT recycling. Independent human CHMP2B mutant experiments impair endosome-to-lysosome delivery and show altered Rab7 access, but do not distinguish CHMP2B performing bilayer fusion from an upstream sorting/recycling contribution. The precise fusion assertion is retained unresolved rather than categorically rejected. |
| GO:0061952 midbody abscission | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | ACCEPT | Summary: Retain the ESCRT contribution to abscission. Reason: The human siRNA survey supports cytokinesis defects following CHMP2B depletion. Direct endogenous midbody localization and CHMP2B membrane deformation provide independent structural context; an autonomous single-protein fission reaction is not claimed. |
| GO:0071985 multivesicular body sorting pathway | IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but... | ACCEPT | Summary: Retain MVB-pathway sorting. Reason: The original experimental source remains unchanged; its incomplete selected cache does not justify a paralog-miscitation allegation. Conserved ESCRT function and independent human target endosomal and membrane-assembly evidence support the pathway. Mutant endolysosomal fusion defects are distinguished from loss of intraluminal sorting, which was intact in PMID:20223751. |
| GO:0090148 membrane fission | NAS PMID:19234443 Membrane scission by the ESCRT-III complex | KEEP AS NON CORE | Summary: Retain membrane fission as contextual ESCRT biology. Reason: The original reconstitution is yeast: Vps2/Vps4 enable recycling and subsequent rounds, while the first scission round does not require Vps2. Independent human CHMP2B deformation and ESCRT-associated budding evidence support the existing broad process, not an isolated autonomous human scission assay. First-round dispensability does not disprove participation; non-core prominence distinguishes this source-specific recycling contribution from the directly demonstrated human membrane-bending activity. |
| GO:0097352 autophagosome maturation | IMP PMID:17984323 Functional multivesicular bodies are required for autophagic... | KEEP AS NON CORE | Summary: Retain autophagosome-maturation context. Reason: The full study measures clearance defects and accumulated autophagic structures after disease-linked CHMP2B expression. It does not isolate a WT CHMP2B reaction sealing phagophores or establish the exact site where the maturation pathway fails. Supporting Evidence: |
| GO:1901673 regulation of mitotic spindle assembly | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | KEEP AS NON CORE | Summary: Retain the spindle-assembly phenotype. Reason: CHMP2B depletion yields multipolar spindle and centrosome abnormalities in human cells. The study leaves the direct mechanistic route unresolved, so the process is retained as contextual rather than a second motor or microtubule-binding core. Supporting Evidence: |
| GO:1902774 late endosome to lysosome transport | IMP PMID:17984323 Functional multivesicular bodies are required for autophagic... | KEEP AS NON CORE | Summary: Retain late-endosomal delivery to lysosomes. Reason: The source connects disease-linked CHMP2B perturbation to impaired degradative trafficking. Independent human fibroblast/cell work identifies defective fusion and Rab7 access while intraluminal sorting is retained; no intrinsic fusase activity follows from these experiments. |
| GO:1904930 amphisome membrane | IDA PMID:17984323 Functional multivesicular bodies are required for autophagic... | UNDECIDED | Summary: The compartment-specific target localization is unresolved. Reason: The full original main article was read. Its CHMP2B truncation experiments show defective clearance and altered LC3/p62 structures; the inspected ultrastructural membrane labels are p62, not a target-specific CHMP2B localization assay. The accessible supplemental description does not resolve endogenous CHMP2B on this exact membrane. Preserve the curator assertion without claiming a wrong-gene error or excluding transient association. |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | UNDECIDED | Summary: Cadherin binding is not resolved by the inspected proximity screen. Reason: The original HDA assertion is preserved. PMID:25468996 uses E-cadherin–BirA proximity biotinylation and explicitly defines a surrounding proteome; proximity need not be physical binding. The target-specific supplementary row and an orthogonal CHMP2B–cadherin binding assay were not recovered. No negative interaction result is asserted. Supporting Evidence: |
| GO:0016236 macroautophagy | TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | KEEP AS NON CORE | Summary: Retain broad macroautophagy involvement as contextual. Reason: The original TAS review source is retained. Primary CHMP2B mutant and ESCRT perturbation studies support endolysosomal/autophagic clearance effects, but do not establish a distinct autonomous macroautophagy molecular function. |
| GO:0061763 multivesicular body-lysosome fusion | TAS PMID:21118109 The role of ESCRT proteins in fusion events involving lysoso... | UNDECIDED | Summary: The exact MVB–lysosome fusion role remains unresolved. Reason: The original review discusses ESCRT-associated fusion phenotypes. Actual human mutant experiments show blocked delivery/fusion and reduced Rab7 recruitment, but do not settle whether WT CHMP2B performs fusion rather than enabling an upstream membrane-remodeling and recycling step. This precise assignment remains unresolved. |
| GO:0005737 cytoplasm | IDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | ACCEPT | Summary: Retain cytoplasmic localization. Reason: The exact GFP localization row from the E-cadherin screen was not recovered. Independent endogenous human-cell staining and low-expression/endogenous-tag imaging directly support a cytoplasmic pool, so the original location is retained with that source-specific access limit. |
| GO:0006914 autophagy | TAS PMID:24095276 Syntaxin 13, a genetic modifier of mutant CHMP2B in frontote... | KEEP AS NON CORE | Summary: Retain a contextual autophagy pathway connection. Reason: The actual primary work uses Drosophila CHMP2BIntron5 genetic interactions and syntaxin-dependent maturation assays. It does not demonstrate direct WT CHMP2B–syntaxin binding or a unique CHMP2B fusion activity. The existing broad process is retained with mutant and species limits. Supporting Evidence: |
| GO:0000815 ESCRT III complex | TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: Retain ESCRT-III complex membership. Reason: The cited reviews provide complex context. Independent endogenous human immunogold and target assembly experiments substantiate CHMP2B membership; this does not confer ATPase activity or the specific enzymatic functions of other ESCRT partners. |
| GO:0006914 autophagy | TAS PMID:17683935 ESCRT-III dysfunction causes autophagosome accumulation and ... | KEEP AS NON CORE | Summary: Retain the mutant-linked autophagy connection. Reason: The authentic abstract reports autophagosome accumulation after CHMP2BIntron5 expression in neurons and flies. Its comparison of mutant versus WT binding and independent full primary clearance studies support a contextual pathway role, not an intrinsic autophagosome-closing reaction. Full original Methods were not recovered. |
| GO:0036258 multivesicular body assembly | TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: Retain MVB assembly as a conserved structural role. Reason: The review-level source is supported by independent target membrane deformation and the conserved endosomal ESCRT machinery. This is not an assertion that every membrane tube is an autonomous scission intermediate. |
| GO:0039702 viral budding via host ESCRT complex | TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | KEEP AS NON CORE | Summary: Retain contextual ESCRT-dependent viral budding. Reason: Independent human CHMP2B single and combinatorial depletion assays support a role in HIV-1 release. Viral exploitation remains contextual, and the more prominent CHMP2A role in some EIAV experiments is kept distinct. |
| GO:1904903 ESCRT III complex disassembly | NAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | KEEP AS NON CORE | Summary: Retain ESCRT disassembly through VPS4 recruitment. Reason: CHMP2B contains a C-terminal MIT-interacting motif that binds VPS4 ATPases. This supplies a recruitment interface supporting recycling; VPS4 performs ATP hydrolysis and subunit extraction. Neither the fact that CHMP2B is disassembled nor generic complex membership alone is used as the justification. |
| GO:0000815 ESCRT III complex | TAS PMID:21118109 The role of ESCRT proteins in fusion events involving lysoso... | ACCEPT | Summary: Retain ESCRT-III complex membership. Reason: The cited reviews provide complex context. Independent endogenous human immunogold and target assembly experiments substantiate CHMP2B membership; this does not confer ATPase activity or the specific enzymatic functions of other ESCRT partners. |
| GO:0006914 autophagy | TAS PMID:21118109 The role of ESCRT proteins in fusion events involving lysoso... | KEEP AS NON CORE | Summary: Retain a broad autophagy contribution. Reason: The review-level source summarizes endolysosomal/autophagic defects. Independent full primary studies support that connection, while the specific fusion or membrane-closure step remains unresolved. |
| GO:0005515 protein binding | IPI PMID:17683935 ESCRT-III dysfunction causes autophagosome accumulation and ... | KEEP AS NON CORE | Summary: Retain the source-specific mouse Chmp4b association. Reason: The original partner is mouse Q9D8B3 (mSnf7-2/Chmp4b). The authentic abstract explicitly reports WT CHMP2B binding and stronger mutant association; full Methods and exact construct recipe remain inaccessible. Independent human CHMP4B co-IP corroborates the conserved association without rewriting the mouse source or pretending all constructs were WT. Retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, which preserves supported generic binding when no better evidence-backed term is established. |
| GO:0000815 ESCRT III complex | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: Retain directly observed ESCRT-III membership. Reason: The full primary Figure 2 immunogold labels endogenous human CHMP2B on plasma-membrane ESCRT spirals trapped by VPS4 depletion. This is deep-etch electron microscopy, not cryo-EM or an atomic CHMP2B structure. Supporting Evidence: |
| GO:0005737 cytoplasm | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: Retain cytoplasmic distribution. Reason: The study directly compares diffuse endogenous CHMP2B staining in control cells with punctate membrane assemblies after VPS4 depletion. The soluble pool and membrane-associated active state are compatible. Supporting Evidence: |
| GO:0005768 endosome | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: Retain endosome association. Reason: The paper shows target redistribution to intracellular endosome-like puncta upon VPS4 depletion, while steady-state endogenous signal is diffuse. The existing compartment is retained without claiming constitutive exclusive endosomal residence. Supporting Evidence: |
| GO:0019076 viral release from host cell | IMP PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in... | KEEP AS NON CORE | Summary: Retain CHMP2B contribution to HIV-1 release. Reason: Actual single CHMP2B depletion modestly reduces infectivity; combined CHMP2A/B depletion has a much stronger effect. Release and infectivity assays support a redundant host-ESCRT contribution rather than an indispensable unique viral receptor function. Supporting Evidence: |
| GO:0019076 viral release from host cell | IGI PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in... | KEEP AS NON CORE | Summary: Retain the two combinatorial viral-release assertions. Reason: The historical unscoped IGI aggregate is preserved; current assertions separately identify CHMP2A and CHMP3. The actual double-depletion assays support genetic contributions, with stronger effects for some combinations. These are not binary binding experiments or proof that CHMP2B alone is required for every virus. This retained historical aggregate duplicates the corresponding appended current scoped assertions for provenance; it is not counted as an additional current GOA assertion. Supporting Evidence: |
| GO:0039702 viral budding via host ESCRT complex | IMP PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in... | KEEP AS NON CORE | Summary: Retain contextual viral ESCRT budding. Reason: The paper directly tests CHMP2B depletion and combinations with CHMP2A/CHMP3. It supports viral use of host ESCRT function, while its CHMP2A–CHMP3 polymer reconstruction is not assigned to CHMP2B. Supporting Evidence: |
| GO:0070050 neuron cellular homeostasis | IMP PMID:16807408 ALS phenotypes with mutations in CHMP2B (charged multivesicu... | KEEP AS NON CORE | Summary: Retain neuron-homeostasis context with clinical limits. Reason: This is a human ALS mutation/phenotype source, available as an authentic abstract. It supports disease-linked neuronal maintenance context, not a defined biochemical function or proof that every reported allele has identical loss-of-function effects. Full target experiments remain access-limited. Supporting Evidence: |
| GO:0005764 lysosome | IDA PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B i... | KEEP AS NON CORE | Summary: Retain the original endolysosomal compartment context. Reason: The original FTD mutation paper is abstract-limited here, so no source-panel reconstruction is claimed. Independent full patient-fibroblast and tagged human-cell experiments support endolysosomal association/abnormalities. WT distribution is largely diffuse and mutant accumulation must not be generalized to constitutive WT residence in every compartment. |
| GO:0005770 late endosome | IDA PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B i... | KEEP AS NON CORE | Summary: Retain the original endolysosomal compartment context. Reason: The original FTD mutation paper is abstract-limited here, so no source-panel reconstruction is claimed. Independent full patient-fibroblast and tagged human-cell experiments support endolysosomal association/abnormalities. WT distribution is largely diffuse and mutant accumulation must not be generalized to constitutive WT residence in every compartment. |
| GO:0005829 cytosol | IDA PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B i... | ACCEPT | Summary: Retain the cytosolic pool with independent corroboration. Reason: The original source remains intact despite incomplete original-body access. Independent endogenous and low-expression human target imaging establishes a cytosolic pool, separate from mutant membrane/endosomal accumulation. |
| GO:0007032 endosome organization | IMP PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B i... | KEEP AS NON CORE | Summary: Retain endosome organization at phenotype scope. Reason: Human disease-linked CHMP2B mutations cause endosomal abnormalities. Independent full patient-fibroblast and cell experiments corroborate altered endolysosomal organization and delivery. These phenotypes do not establish that every mutation abolishes intraluminal-vesicle sorting. |
| GO:0050890 cognition | IMP PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B i... | KEEP AS NON CORE | Summary: Retain cognition as a distal disease-associated process. Reason: The original human FTD mutation study supports a cognitive disease connection. The exact source is abstract-limited; cognition is retained as a contextual phenotype and not used to define a molecular activity or a new direct cognitive mechanism. Supporting Evidence: |
| GO:0070050 neuron cellular homeostasis | IMP PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B i... | KEEP AS NON CORE | Summary: Retain neuronal maintenance as disease context. Reason: The original human FTD source and independent mutant/neuronal studies support this broad process. Mutant accumulation and neurotoxicity are distinguished from the normal membrane-remodeling function; no uniform loss-of-function mechanism across variants is inferred. |
| GO:0010824 regulation of centrosome duplication | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | KEEP AS NON CORE | Summary: Retain centrosome-duplication regulation at broad phenotype scope. Reason: The human siRNA study observes excess centrosomes after CHMP2B depletion, but does not resolve overduplication, fragmentation, or clustering mechanisms for this target. The original regulatory annotation is retained without a direct centrosome enzyme or structural-core claim. Supporting Evidence: |
| GO:0039702 viral budding via host ESCRT complex | IGI PMID:24107264 ESCRT requirements for EIAV budding | KEEP AS NON CORE | Summary: Retain a cooperative contribution to EIAV budding. Reason: Full Results and Methods identify CHMP2A as the stronger single contributor in 293T cells, with CHMP2B co-depletion further enhancing the defect. Subsequent CHMP2 rescue/interface tests chiefly use CHMP2A. The source therefore supports a cooperative CHMP2B contribution, not relabeling CHMP2A-specific experiments as CHMP2B. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | UNDECIDED | Summary: The exact prostatic-exosome target row remains unresolved. Reason: The full main proteomics paper and isolation/MS methods were read, but the original supplementary CHMP2B target row was not recovered. Independent urinary-exosome detection supports the broader compartment but does not reconstruct this prostatic-source assertion. No claim of contamination or active secretion follows from the access gap. |
| GO:0005515 protein binding | IPI PMID:21975012 ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate... | KEEP AS NON CORE | Summary: Retain measured human CHMP4B association. Reason: Full Figure 6A reports Flag-CHMP2B pull-down of endogenous hSnf7-2/CHMP4B in human HEK293T cells. This is complex-context association, not a purified binary interface, and unrelated Snf7 depletion phenotypes are not transferred to CHMP2B. Retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, which preserves supported generic binding when no better evidence-backed term is established. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Retain urinary-exosome proteomic detection. Reason: The authentic author-hosted urinary-exosome database lists CHMP2B/NP_054762 with four peptides. This supports protein detection in the isolated vesicle preparation, not a classical secretion signal, an exosome-specific molecular function, or proof of luminal topology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3159232 | ACCEPT | Summary: Retain the cytosolic pool recorded by Reactome. Reason: The authenticated event-participant records include CHMP2B as a constituent of the relevant ESCRT pool/assembly. This is own-source pathway provenance, not an independent target localization experiment or a claim that CHMP2B catalyzes the event named in the title. Independent human imaging supports the cytosolic pool. Supporting Evidence: Reactome:R-HSA-3159232 file:human/CHMP2B/CHMP2B-source-evidence.json |
| GO:0005829 cytosol | TAS Reactome:R-HSA-917693 | ACCEPT | Summary: Retain the cytosolic pool recorded by Reactome. Reason: The authenticated event-participant records include CHMP2B as a constituent of the relevant ESCRT pool/assembly. This is own-source pathway provenance, not an independent target localization experiment or a claim that CHMP2B catalyzes the event named in the title. Independent human imaging supports the cytosolic pool. Supporting Evidence: Reactome:R-HSA-917693 file:human/CHMP2B/CHMP2B-source-evidence.json |
| GO:0005829 cytosol | TAS Reactome:R-HSA-917700 | ACCEPT | Summary: Retain the cytosolic pool recorded by Reactome. Reason: The authenticated event-participant records include CHMP2B as a constituent of the relevant ESCRT pool/assembly. This is own-source pathway provenance, not an independent target localization experiment or a claim that CHMP2B catalyzes the event named in the title. Independent human imaging supports the cytosolic pool. Supporting Evidence: Reactome:R-HSA-917700 file:human/CHMP2B/CHMP2B-source-evidence.json |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668389 | ACCEPT | Summary: Retain independently supported cytosolic localization. Reason: The exact Reactome participant sets contain CHMP2B within nuclear-envelope complexes. They establish event/complex membership, not a separate cytosolic pool in this event. The original TAS source is preserved, while independent human CHMP2B imaging in PMID:24878737 and PMID:42349418 supports the retained cytosol location. Neither the event title nor another component's reaction is transferred to CHMP2B. Supporting Evidence: Reactome:R-HSA-9668389 file:human/CHMP2B/CHMP2B-source-evidence.json |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668395 | ACCEPT | Summary: Retain independently supported cytosolic localization. Reason: The exact Reactome participant sets contain CHMP2B within nuclear-envelope complexes. They establish event/complex membership, not a separate cytosolic pool in this event. The original TAS source is preserved, while independent human CHMP2B imaging in PMID:24878737 and PMID:42349418 supports the retained cytosol location. Neither the event title nor another component's reaction is transferred to CHMP2B. Supporting Evidence: Reactome:R-HSA-9668395 file:human/CHMP2B/CHMP2B-source-evidence.json |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668398 | ACCEPT | Summary: Retain the cytosolic pool recorded by Reactome. Reason: The authenticated event-participant records include CHMP2B as a constituent of the relevant ESCRT pool/assembly. This is own-source pathway provenance, not an independent target localization experiment or a claim that CHMP2B catalyzes the event named in the title. Independent human imaging supports the cytosolic pool. Supporting Evidence: Reactome:R-HSA-9668398 file:human/CHMP2B/CHMP2B-source-evidence.json |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668405 | ACCEPT | Summary: Retain independently supported cytosolic localization. Reason: The exact Reactome participant sets contain CHMP2B within nuclear-envelope complexes. They establish event/complex membership, not a separate cytosolic pool in this event. The original TAS source is preserved, while independent human CHMP2B imaging in PMID:24878737 and PMID:42349418 supports the retained cytosol location. Neither the event title nor another component's reaction is transferred to CHMP2B. Supporting Evidence: Reactome:R-HSA-9668405 file:human/CHMP2B/CHMP2B-source-evidence.json |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668415 | ACCEPT | Summary: Retain the cytosolic pool recorded by Reactome. Reason: The authenticated event-participant records include CHMP2B as a constituent of the relevant ESCRT pool/assembly. This is own-source pathway provenance, not an independent target localization experiment or a claim that CHMP2B catalyzes the event named in the title. Independent human imaging supports the cytosolic pool. Supporting Evidence: Reactome:R-HSA-9668415 file:human/CHMP2B/CHMP2B-source-evidence.json |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668419 | ACCEPT | Summary: Retain independently supported cytosolic localization. Reason: The exact Reactome participant sets contain CHMP2B within nuclear-envelope complexes. They establish event/complex membership, not a separate cytosolic pool in this event. The original TAS source is preserved, while independent human CHMP2B imaging in PMID:24878737 and PMID:42349418 supports the retained cytosol location. Neither the event title nor another component's reaction is transferred to CHMP2B. Supporting Evidence: Reactome:R-HSA-9668419 file:human/CHMP2B/CHMP2B-source-evidence.json |
| GO:0019904 protein domain specific binding | IPI PMID:17928862 ESCRT-III recognition by VPS4 ATPases | MODIFY | Summary: Specify binding to the VPS4 ATPases. Reason: The actual source resolves the CHMP2B C-terminal peptide (195–213) bound to VPS4 MIT domains by structural/binding experiments. VPS4A and VPS4B are ATPases, so ATPase binding is more informative than domain binding without transferring hydrolysis to CHMP2B. The historical aggregate remains intact; current VPS4A/B partner assertions are appended separately. This retained historical aggregate duplicates the corresponding appended current scoped assertions for provenance; it is not counted as an additional current GOA assertion. Proposed replacements: ATPase binding Supporting Evidence: PMID:17928862 human VPS4A and VPS4B bind conserved file:human/CHMP2B/CHMP2B-source-evidence.json |
| GO:0000815 ESCRT III complex | NAS PMID:36107470 Comprehensive analysis of the human ESCRT-III-MIT domain int... | ACCEPT | Summary: Retain the newly retrieved ESCRT-III membership assertion. Reason: This is a genuine current NAS annotation, not an authored NEW. The source surveys the human ESCRT-III/MIT system; independent endogenous CHMP2B immunogold and polymerization evidence support membership. C-terminal peptide interactions do not by themselves define an invariant assembled holo-complex. |
| GO:0005643 nuclear pore | IDA PMID:26040713 ESCRT-III controls nuclear envelope reformation | MODIFY | Summary: Refine the location to the nuclear envelope. Reason: GO:0005643 denotes the nuclear pore complex. Full PMID:26040713 Figures 1A/1B and Extended Data Figure 1A directly localize endogenous human CHMP2B to the reforming nuclear envelope, while the separate CHMP2A ultrastructural analysis distinguishes non-NPC sealing channels. The broader envelope compartment is positively supported; the exact original NPC-incorporation basis remains unresolved. MODIFY is a reviewer recommendation of that supported location, not a reissued part_of assertion of stable complex incorporation. The genuine current IDA source and archived qualifier remain unchanged. Proposed replacements: nuclear envelope Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22046132 The SARS-coronavirus-host interactome: identification of cyc... | KEEP AS NON CORE | Summary: Retain the source-specific SARS nsp1 association. Reason: This fully scoped assertion retains the exact processed nsp1 product identifier. Literal MINT records support a positive pooling-Y2H result and a tagged mammalian LUMIER result with Z-score 1.3, above the source threshold of 1. The assay evidence establishes contextual association, not a native infection mechanism or virion binding. Retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, which preserves supported generic binding when no better evidence-backed term is established. |
| GO:0005515 protein binding | IPI PMID:22046132 The SARS-coronavirus-host interactome: identification of cyc... | KEEP AS NON CORE | Summary: Retain the source-specific SARS nsp9 association. Reason: This fully scoped assertion retains the exact processed nsp9 product identifier. Literal MINT records support a positive pooling-Y2H result and a tagged mammalian LUMIER result with Z-score 1.1, above the source threshold of 1. The assay evidence establishes contextual association, not a native infection mechanism or virion binding. Retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, which preserves supported generic binding when no better evidence-backed term is established. |
| GO:0005515 protein binding | IPI PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in... | KEEP AS NON CORE | Summary: Retain direct CHMP4B binding. Reason: The actual PMID:23051622 SPR assay tests full-length C-terminal His-tagged human CHMP2B against a defined CHMP4B construct, with negative-channel correction. The exact current partner accession is retained. This establishes binding at the tested construct scope; the CHMP2A–CHMP3 cryo-EM tube is a separate experiment. Retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, which preserves supported generic binding when no better evidence-backed term is established. |
| GO:0005515 protein binding | IPI PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in... | KEEP AS NON CORE | Summary: Retain direct CHMP3 binding. Reason: The actual PMID:23051622 SPR assay tests full-length C-terminal His-tagged human CHMP2B against a defined CHMP3 construct, with negative-channel correction. The exact current partner accession is retained. This establishes binding at the tested construct scope; the CHMP2A–CHMP3 cryo-EM tube is a separate experiment. Retained as non-core under projects/CLINGEN_MENDELIAN.md, Curation instructions, which preserves supported generic binding when no better evidence-backed term is established. |
| GO:0005886 plasma membrane | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: Retain the colocalizes_with plasma-membrane assertion. Reason: Endogenous CHMP2B immunogold labeling and unroofed-cell imaging in PMID:24878737 place the target on membrane-associated ESCRT spirals after VPS4 depletion. This is deep-etch EM in a trapped-assembly condition. The original colocalizes_with qualifier is retained exactly; it is not silently upgraded to stable membrane incorporation. Supporting Evidence: |
| GO:0005886 plasma membrane | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: Retain the located_in plasma-membrane assertion. Reason: Endogenous CHMP2B immunogold labeling and unroofed-cell imaging in PMID:24878737 place the target on membrane-associated ESCRT spirals after VPS4 depletion. This is deep-etch EM in a trapped-assembly condition. The original located_in qualifier is retained exactly; it is not silently upgraded to stable membrane incorporation. Supporting Evidence: |
| GO:0019076 viral release from host cell | IGI PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in... | KEEP AS NON CORE | Summary: Retain the CHMP2B/CHMP2A combinatorial viral-release assertion. Reason: The actual PMID:23051622 combined-depletion experiment with CHMP2A supports a genetic contribution to HIV release. The exact current WITH/FROM partner is preserved. These are perturbation assays rather than binary-binding tests, and they do not establish that CHMP2B alone is indispensable for every virus. Supporting Evidence: |
| GO:0019076 viral release from host cell | IGI PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in... | KEEP AS NON CORE | Summary: Retain the CHMP2B/CHMP3 combinatorial viral-release assertion. Reason: The actual PMID:23051622 combined-depletion experiment with CHMP3 supports a genetic contribution to HIV release. The exact current WITH/FROM partner is preserved. These are perturbation assays rather than binary-binding tests, and they do not establish that CHMP2B alone is indispensable for every virus. Supporting Evidence: |
| GO:0019904 protein domain specific binding | IPI PMID:17928862 ESCRT-III recognition by VPS4 ATPases | MODIFY | Summary: Specify binding to the VPS4B ATPase. Reason: The original source resolves binding of the CHMP2B C-terminal MIT-interacting peptide to VPS4B, using structural/binding experiments. The exact current partner is preserved. ATPase binding is more informative than generic domain binding and describes the partner class; it does not assign ATP hydrolysis to CHMP2B. Proposed replacements: ATPase binding Supporting Evidence: PMID:17928862 Structures of VPS4A MIT-CHMP1A and VPS4B MIT-CHMP2B complexes reveal file:human/CHMP2B/CHMP2B-source-evidence.json |
| GO:0019904 protein domain specific binding | IPI PMID:17928862 ESCRT-III recognition by VPS4 ATPases | MODIFY | Summary: Specify binding to the VPS4A ATPase. Reason: The original source resolves binding of the CHMP2B C-terminal MIT-interacting peptide to VPS4A, using structural/binding experiments. The exact current partner is preserved. ATPase binding is more informative than generic domain binding and describes the partner class; it does not assign ATP hydrolysis to CHMP2B. Proposed replacements: ATPase binding Supporting Evidence: PMID:17928862 human VPS4A and VPS4B bind conserved file:human/CHMP2B/CHMP2B-source-evidence.json |
| GO:0180020 membrane bending activity | IDA PMID:21926173 Charged multivesicular body protein 2B (CHMP2B) of the endos... | NEW | Summary: Propose the directly measured membrane-deformation activity. Reason: Human CHMP2B WT/C-terminal-tag constructs deform membranes into tubes, with N-terminal-tag and L4D/F5D controls. Purified human CHMP2B 1–154 after CHMP4B assembly independently deforms defined liposomes. The activity is sensitive to activation, tagging, lipid composition and geometry; autonomous universal scission or restriction of a fenestration is not established. This MF proposal replaces the prior authored grommet claim; no machine annotation is rewritten. |
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Download this section (compressed HTML)Q: Which target-specific assays underlie the original CHMP2B kinetochore/microtubule and autophagosome/lysosome/amphisome membrane annotations? The inspected panels do not resolve those scopes, but absence is not established.
Q: Does CHMP2B directly participate in a bilayer-fusion step, or do persistent ESCRT assemblies and altered Rab7 access explain the endolysosomal fusion phenotypes?
Q: Which native CHMP2B assemblies deform membranes, promote scission, or restrict fenestrations under defined physiological geometries? Bending is directly supported; these outcomes are not interchangeable.
Q: How do the two current products differ in membrane remodeling and VPS4 recruitment, and what sequence underlies the 2021 full-length construct numbered 1–222?
Q: Can the exact original prostatic-exosome and E-cadherin-proximity target tables be recovered and orthogonally corroborated?
Experiment: Compare sequence-verified native products, WT full-length and defined activated constructs in matched membrane deformation and scission assays, retaining CHMP4/VPS4 order-of-addition controls.
Hypothesis: CHMP2B membrane deformation and VPS4-dependent turnover depend on activation state and membrane geometry.
Experiment: Use endogenous CHMP2B labeling and validated orthogonal antibodies with compartment markers, separating WT from pathogenic truncations and distinguishing NPC incorporation from nuclear-envelope recruitment.
Hypothesis: The unresolved compartment annotations represent transient target pools or source-specific scope differences.
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