CHMP2B

Existing Annotations Review

Core Functions

CHMP2B is a core subunit of the ESCRT-III complex that mediates membrane fission during intraluminal vesicle formation in MVBs.

Molecular Function:

membrane grommet activity

Directly Involved In:

multivesicular body sorting pathway

Cellular Locations:

multivesicular body multivesicular body membrane

In Complex:

ESCRT III complex

Supporting Evidence:

PMID:19234443
Three subunits of ESCRT-III, Vps20, Snf7, and Vps24, were sufficient to detach intralumenal vesicles

CHMP2B performs membrane fission at the midbody during cytokinetic abscission.

Molecular Function:

membrane grommet activity

Directly Involved In:

midbody abscission

Cellular Locations:

midbody

In Complex:

ESCRT III complex

Supporting Evidence:

PMID:20616062
depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission

CHMP2B mediates membrane sealing during nuclear envelope reformation at telophase.

Molecular Function:

membrane grommet activity

Directly Involved In:

nuclear membrane reassembly

In Complex:

ESCRT III complex

Supporting Evidence:

PMID:26040713
the endosomal sorting complex required for transport-III (ESCRT-III) machinery localizes to sites of annular fusion in the forming NE in human cells

CHMP2B mediates membrane fission during viral budding at the plasma membrane.

Molecular Function:

membrane grommet activity

Directly Involved In:

viral budding via host ESCRT complex

Cellular Locations:

plasma membrane

In Complex:

ESCRT III complex

Supporting Evidence:

PMID:24878737
Structure of cellular ESCRT-III spirals and their relationship to HIV budding

CHMP2B mediates membrane sealing during phagophore closure.

Molecular Function:

membrane grommet activity

Directly Involved In:

autophagosome maturation

Cellular Locations:

autophagosome membrane

In Complex:

ESCRT III complex

Supporting Evidence:

PMID:17984323
autophagic degradation is inhibited in cells depleted of ESCRT subunits and in cells expressing CHMP2B mutants

CHMP2B binds VPS4 ATPases through its MIT-interacting motif (MIM), enabling ESCRT-III complex disassembly.

Molecular Function:

protein domain specific binding

Directly Involved In:

ESCRT III complex disassembly

Cellular Locations:

cytosol

In Complex:

ESCRT III complex

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

CHMP2B contains the Snf7 domain which maps to vacuolar transport function

GO_REF:0000033

Annotation inferences using phylogenetic trees

CHMP2B function as an ESCRT-III subunit is conserved across eukaryotes

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

Protein transport keyword maps to GO:0015031

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping

CHMP2B subcellular location annotations derived from UniProt

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

ARBA predictions for CHMP2B localization and function generally accurate

PMID:16041373

Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia

First identification of CHMP2B mutations in FTD
CHMP2B localizes to late endosomes, lysosomes, and cytosol
Mutations cause enlarged endosomes and neuronal dysfunction

PMID:16505166

Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1

ESCRT-III subunits are recycled by VPS4 for multiple rounds of MVB formation

PMID:16554368

The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptor

ESCRT-III localizes to MVB membranes
Required for MVB sorting pathway function

PMID:16730941

A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex.

CHMP2B interacts with CHMP3 and other ESCRT-III subunits
MIT domain-containing proteins bind to multiple ESCRT-III components

PMID:16807408

ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B).

CHMP2B mutations cause ALS phenotypes
Expands disease spectrum beyond FTD

PMID:17683935

ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration.

CHMP2B is required for autophagy

PMID:17928862

ESCRT-III recognition by VPS4 ATPases

Structure of CHMP2B MIT-interacting motif with VPS4B
CHMP2B binds VPS4A and VPS4B for complex disassembly

PMID:17984323

Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease

ESCRT depletion or CHMP2B mutants inhibit autophagy
Causes accumulation of ubiquitin/p62-positive aggregates
CHMP2B mutations disrupt TDP-43 clearance
Links ESCRT dysfunction to neurodegeneration

PMID:19056867

Large-scale proteomics and phosphoproteomics of urinary exosomes

CHMP2B detected in urinary exosome proteome

PMID:19234443

Membrane scission by the ESCRT-III complex

ESCRT-III alone can drive membrane fission
Three ESCRT-III subunits sufficient for vesicle detachment
VPS4 required for recycling, not scission

PMID:20588296

Membrane budding and scission by the ESCRT machinery: it's all in the neck.

Review of ESCRT-III mechanism in membrane remodeling

PMID:20616062

Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance

ESCRT-III depletion inhibits abscission
Also affects centrosome and spindle maintenance
VPS4 localizes to spindle poles and midbodies

PMID:21118109

The role of ESCRT proteins in fusion events involving lysosomes, endosomes and autophagosomes.

CHMP2B participates in autophagy and MVB-lysosome fusion

PMID:21975012

ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate transmembrane cargos in hESC-derived human neurons.

CHMP2B interacts with CHMP4B for ESCRT-III assembly

PMID:22046132

The SARS-coronavirus-host interactome: identification of cyclophilins as target for pan-coronavirus inhibitors.

CHMP2B interacts with viral Rep proteins

PMID:23051622

ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding

ESCRT-III forms helical polymers
CHMP2A and CHMP3 act synergistically in viral budding

PMID:23533145

In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine

CHMP2B detected in exosome proteome

PMID:24095276

Syntaxin 13, a genetic modifier of mutant CHMP2B in frontotemporal dementia, is required for autophagosome maturation

Syntaxin 13 is a genetic modifier of CHMP2B
Both are required for autophagosome maturation

PMID:24107264

ESCRT requirements for EIAV budding

ESCRT-III required for equine lentivirus budding

PMID:24482116

ESCRT machinery is required for plasma membrane repair

ESCRT performs membrane sealing during plasma membrane repair

PMID:24878737

Structure of cellular ESCRT-III spirals and their relationship to HIV budding

Cryo-EM structure of ESCRT-III spirals
Direct visualization at HIV budding sites

PMID:25468996

E-cadherin interactome complexity and robustness resolved by quantitative proteomics

CHMP2B detected in E-cadherin interactome

PMID:26040712

Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing

ESCRT-III recruited to NE during anaphase
Coordinates with spastin for spindle disassembly
Localizes to kinetochores and midbody

PMID:26040713

ESCRT-III controls nuclear envelope reformation

CHMP2A/B encircle forming daughter nuclei during telophase
ESCRT-III localizes to sites of annular fusion
Required for NE integrity and sealing

PMID:26496610

A human interactome in three quantitative dimensions organized by stoichiometries and abundances

CHMP2B-CHMP4B interaction confirmed

Reactome:R-HSA-3159232

Recruitment Of HIV Virion Budding Machinery

CHMP2B participates in HIV budding pathway

Reactome:R-HSA-917693

ESCRT Disassembly

CHMP2B is recycled by VPS4

Reactome:R-HSA-917700

MVB Vesicle Formation

CHMP2B functions in MVB formation

Reactome:R-HSA-9668389

VPS4 binds ESCRT-III assemblies at nuclear envelope (NE) fenestrations

CHMP2B participates in NE sealing pathway

Reactome:R-HSA-9668395

CHMP7 binds CC2D1B

CHMP2B in ESCRT-III NE recruitment pathway

Reactome:R-HSA-9668398

CHMP7 binds CHMP4B, which recruits other subunits of the ESCRT-III complex

CHMP2B recruited as part of ESCRT-III assembly at NE

Reactome:R-HSA-9668405

SPAST (spastin) binds the IST1 subunit of ESCRT-III at the sites of microtubule attachment to chromatin

CHMP2B in pathway with spastin and IST1

Reactome:R-HSA-9668415

VPS4 mediates disassembly of ESCRTIII subunits to promote sealing of holes in the nuclear envelope

CHMP2B disassembled by VPS4 during NE sealing

Reactome:R-HSA-9668419

SPAST (spastin) mediates the severing of microtubules at chromosome attachment sites

CHMP2B in pathway coordinating spindle disassembly and NE sealing

PMID:21044950

Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells.

CHMP2B interacts with TERF2IP in yeast two-hybrid screen

file:human/CHMP2B/CHMP2B-deep-research-falcon.md

Deep research report on CHMP2B

Suggested Experiments

Experiment: Structural studies of CHMP2B in the context of full ESCRT-III polymers at near-atomic resolution

Experiment: Live-cell imaging of CHMP2B dynamics during nuclear envelope reformation

Experiment: Proteomics of CHMP2B interactome in neurons versus non-neuronal cells

Deep Research

Falcon

(CHMP2B-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 28 citations 2025-12-27T23:24:08.737421

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Plan overview: We verified the gene/protein identity (CHMP2B, UniProt Q9UQN3), then gathered recent (2023–2024) peer‑reviewed literature on ESCRT‑III function, post‑translational regulation, cellular localizations, and FTD/ALS disease mechanisms, plus clinical biomarker and natural‑history data from the Danish CHMP2B pedigree. We prioritize primary studies and recent reviews, include URLs and publication dates, and cite each major claim.

Comprehensive research report: Human CHMP2B (Q9UQN3)

1) Key concepts and definitions
- Identity and family: CHMP2B (charged multivesicular body protein 2B) is a human ESCRT‑III subunit in the evolutionarily conserved SNF7/ESCRT‑III family that assembles on membranes to remodel and ultimately sever membrane necks; CHMP2B mutations are established genetic causes of familial frontotemporal dementia/ALS (FTD/ALS) (Nucleus, 2024; review) (keeley2024nuclearanddegradative pages 1-3). This places CHMP2B in the ESCRT pathway that drives intraluminal vesicle (ILV) formation in multivesicular bodies (MVBs), membrane repair, and other reverse‑topology scission reactions, with disassembly powered by the AAA+ ATPase VPS4 (Nature Communications, 2024) (richard2024methylationofescrtiii pages 1-2).
- Core ESCRT‑III functions: ESCRT‑III polymers assemble at membrane necks; VPS4 remodels/extracts ESCRT‑III subunits to complete scission. ESCRT‑III operates in MVB biogenesis, cytokinetic abscission, nuclear envelope integrity/repair, plasma membrane and lysosomal repair, and autophagy/lysosome pathways (Nucleus, 2024; review) (keeley2024nuclearanddegradative pages 1-3).

2) Molecular function and regulation; recent developments (2023–2024)
- ESCRT‑III dynamics in cytokinesis and viral budding: A 2024 study identified lysine‑6 methylation of CHMP2B by SMYD2 as a regulator of abscission timing. SMYD2 loss or non‑methylatable CHMP2B K6 mutants delay CHMP2B polymerization and abscission; SMYD2 gain accelerates abscission and can bypass the abscission checkpoint. The same K6 methylation also modulates ESCRT‑III‑dependent HIV‑1 budding (Nature Communications, May 2024; https://doi.org/10.1038/s41467-024-47717-3) (richard2024methylationofescrtiii pages 1-2).
- ESCRT‑III in autophagy/mitophagy: ESCRT‑III is required for sealing phagophores/autophagosomes; depletion of ESCRT‑III subunits (including CHMP2 paralogues) impairs mitophagic flux, consistent with ESCRT‑mediated membrane closure before lysosomal fusion (Autophagy, 2020; context for mechanism cited in 2024 reviews) (keeley2024nuclearanddegradative pages 1-3).
- ESCRT‑III in nuclear envelope and lysosomal/plasma membrane repair: Recent synthesis highlights roles for ESCRT‑III in nuclear pore complex surveillance and nuclear envelope repair, as well as lysosomal membrane damage responses—all processes relevant to neuronal survival (Nucleus, 2024; review; May 2024; https://doi.org/10.1080/19491034.2024.2349085) (keeley2024nuclearanddegradative pages 1-3).

3) Cellular and subcellular localization and where CHMP2B acts
- Endosomes/MVBs and endolysosomal system: Disease‑linked CHMP2B mutations cause enlarged endosomes, endolysosomal trafficking defects, and accumulation of autophagic compartments, locating CHMP2B function at the endosome/MVB–lysosome interface (Nucleus, 2024) (keeley2024nuclearanddegradative pages 9-10).
- Cytokinetic bridge (midbody): CHMP2B is part of ESCRT‑III assemblies at the intercellular bridge, where post‑translational methylation by SMYD2 tunes its polymerization and timing of abscission (Nature Communications, 2024) (richard2024methylationofescrtiii pages 1-2).
- Additional sites in neurons: ESCRT‑III functions in synaptic pruning/trafficking and degradative pathways in neurons; alterations in ESCRT‑III (including CHMP2B) are implicated in synaptic dysfunction in FTD/ALS (Nucleus, 2024; review) (keeley2024nuclearanddegradative pages 1-3).

4) Pathway context and interactions
- ESCRT cascade: Adaptor factors and early ESCRTs nucleate ESCRT‑III assembly. CHMP2B participates in ESCRT‑III heteropolymers that constrict membrane necks, with VPS4 catalyzing remodeling/disassembly to complete scission (Nature Communications, 2024; https://doi.org/10.1038/s41467-024-47717-3) (richard2024methylationofescrtiii pages 1-2). Reviews synthesize CHMP2B within ESCRT‑III roles at endosomes/MVBs, nuclear envelope, and lysosomal repair (Nucleus, 2024) (keeley2024nuclearanddegradative pages 1-3).

5) Disease‑associated mutations and mechanisms (FTD/ALS), with recent primary data
- Spectrum of pathogenic variants: Reviews summarize autosomal dominant C‑terminal truncations (e.g., CHMP2BIntron5/Δ10/Q165X) and point mutations (e.g., D148Y, T104N) causing ESCRT‑III dysfunction (Nucleus, 2024) (keeley2024nuclearanddegradative pages 9-10). A 2023 clinical genetics study reported a novel splice‑site variant (c.532‑2A>T) in CHMP2B in the first Chinese family with CHMP2B‑FTD, predicting truncation that removes part of exon 6; clinical presentation included behavioral onset and frontotemporal atrophy (Mol Genet Genomic Med, Jun 2023; https://doi.org/10.1002/mgg3.2222) (li2023anovelsplice‐site pages 3-4).
- Mutation‑specific cellular phenotypes:
• T104N (associated with ALS‑predominant phenotypes) relocalizes CHMP2B from MVB‑like structures to Golgi‑associated aggregates and inhibits neuronal process elongation; aggregation co‑localizes with GM130 and ubiquitin (Neurology International, Aug 2023; https://doi.org/10.3390/neurolint15030063) (shirai2023ftdalstype7associated pages 4-6).
• D148Y (FTD‑linked) accumulates at the Golgi, triggers Golgi stress signaling (↓Hsp47, ↑Arf4), and blunts neurite elongation; rescuable by Hsp47 overexpression or Arf4 knockdown, nominating Golgi stress modulators as therapeutic targets (Current Issues in Molecular Biology, Feb 2024; https://doi.org/10.3390/cimb46020090) (fukatsu2024modulatinggolgistress pages 1-2).
- Endolysosomal/autophagy dysfunction and proteinopathy: ESCRT‑III impairment by CHMP2B mutations is linked to accumulation of autophagic structures, defective endosome‑to‑lysosome fusion, and lysosomal repair responses; CHMP2B‑FTD often lacks classic cytoplasmic TDP‑43 inclusions despite ubiquitin/p62 pathology (Nucleus, 2024; review) (keeley2024nuclearanddegradative pages 9-10).

6) Clinical biomarkers and natural history (applications and real‑world data)
- CSF endo‑lysosomal/proteostasis markers in a genetically homogeneous Danish pedigree: Targeted PRM‑MS in 31 family members (11 symptomatic, 7 presymptomatic carriers, 13 controls) showed lower CSF ubiquitin, cathepsin B (CTSB), and APP, with higher complement C9, lysozyme, and transcobalamin II (TCN2) in mutation carriers. Some markers correlated with CSF/serum ratios, suggesting peripheral contributions; authors hypothesize intracellular sequestration/altered exosome trafficking as a basis for reduced CSF ubiquitin. Neurofilament light (NfL) rises in CSF/serum several years before onset (Alzheimer’s & Dementia: DADM, Jan 2023; https://doi.org/10.1002/dad2.12402) (toft2023endo‐lysosomalproteinconcentrations pages 1-2, toft2023endo‐lysosomalproteinconcentrations pages 5-6, toft2023endo‐lysosomalproteinconcentrations pages 2-3, toft2023endo‐lysosomalproteinconcentrations pages 6-7).
- Natural history in six generations (Danish FTD‑3 pedigree): Mean age at onset 58.9 years (SD 5.9), mean time from onset to institutionalization 5.7 years (SD 3.7), and to death 10.0 years (SD 7.1), with high variability. Elevated mortality (HR 3.84, p<0.0001). Modifiers included earlier onset with higher education and daily alcohol use; paternal transmission associated with earlier onset in women; ApoE ε4/ε4 associated with delayed institutionalization (Acta Neurol Scand, Jan 2022; https://doi.org/10.1111/ane.13578) (roos2022sixgenerationsof pages 9-13, roos2022sixgenerationsof pages 13-18, roos2022sixgenerationsof pages 1-9).
- Network physiology: EEG microstate analysis (fronto‑parietal network; “microstate D”) showed a biphasic change—prolonged duration early after symptom onset then reduced duration later—consistent with evolving fronto‑parietal network dysfunction in CHMP2B‑FTD (Frontiers in Aging Neuroscience, Sep 2021; https://doi.org/10.3389/fnagi.2021.714220) (musaeus2021corticalfrontoparietalnetwork pages 1-2).

7) Expert opinions and authoritative syntheses (2023–2024)
- 2024 review (Nucleus) emphasizes that ESCRT‑III (including CHMP2B) underpins nuclear envelope surveillance/repair and endolysosomal trafficking in human neurons and that CHMP2B mutations produce truncated proteins, enlarged endosomes, and autophagy defects, clarifying mechanisms for FTD/ALS without canonical TDP‑43 pathology (May 2024; https://doi.org/10.1080/19491034.2024.2349085) (keeley2024nuclearanddegradative pages 1-3, keeley2024nuclearanddegradative pages 9-10).
- 2024 mechanistic advance: CHMP2B K6 methylation by SMYD2 is a tunable PTM that gates ESCRT‑III polymerization and abscission timing, and also affects HIV‑1 budding—providing a new regulatory axis with potential therapeutic leverage (May 2024; Nature Communications; https://doi.org/10.1038/s41467-024-47717-3) (richard2024methylationofescrtiii pages 1-2).
- 2024 autophagy‑lysosome perspective: Autophagy‑lysosomal defects, including those from ESCRT‑III perturbation (e.g., CHMP2B), are central in neurodegeneration and aging brains (Nature Reviews Molecular Cell Biology, Aug 2024; https://doi.org/10.1038/s41580-024-00757-5) (keeley2024nuclearanddegradative pages 1-3).

8) Translational directions and current applications
- Biomarker development: The 2023 CHMP2B family CSF study provides candidate endo‑lysosomal biomarkers (C9, lysozyme, TCN2, ubiquitin, CTSB, APP) for presymptomatic and symptomatic stages, complementing NfL; relationships with CSF/serum ratios guide interpretation of central vs peripheral sources (Alzheimer’s & Dementia: DADM, Jan 2023; https://doi.org/10.1002/dad2.12402) (toft2023endo‐lysosomalproteinconcentrations pages 1-2, toft2023endo‐lysosomalproteinconcentrations pages 5-6).
- Genetic counseling and prognosis: The six‑generation cohort quantifies onset, progression, and survival distributions and potential modifiers, informing counseling and clinical trial design in CHMP2B‑FTD (Acta Neurol Scand, Jan 2022; https://doi.org/10.1111/ane.13578) (roos2022sixgenerationsof pages 9-13, roos2022sixgenerationsof pages 13-18).
- Potential therapeutic targets:
• SMYD2–CHMP2B K6 methylation axis to restore/retime ESCRT‑III polymerization in cytokinesis‑related contexts and potentially in other ESCRT‑dependent neuronal processes (Nature Communications, 2024) (richard2024methylationofescrtiii pages 1-2).
• Golgi stress pathway modifiers (Hsp47 upregulation; Arf4 downregulation) rescue neurite phenotypes induced by FTD‑linked CHMP2B mutants (Current Issues in Molecular Biology, Feb 2024; https://doi.org/10.3390/cimb46020090) (fukatsu2024modulatinggolgistress pages 1-2).

9) Quantitative highlights (recent statistics and data)
- CSF proteomic panel in CHMP2B‑FTD: Relative decreases in ubiquitin, APP, CTSB; increases in complement C9, lysozyme, TCN2; NfL increases years pre‑onset (DADM, Jan 2023) (toft2023endo‐lysosomalproteinconcentrations pages 1-2, toft2023endo‐lysosomalproteinconcentrations pages 5-6, toft2023endo‐lysosomalproteinconcentrations pages 2-3, toft2023endo‐lysosomalproteinconcentrations pages 6-7).
- Natural history metrics in Danish CHMP2B‑FTD: mean age at onset 58.9 years; mean onset→institutionalization 5.7 years; mean onset→death 10.0 years; HR for mortality 3.84 (Acta Neurol Scand, Jan 2022) (roos2022sixgenerationsof pages 9-13, roos2022sixgenerationsof pages 13-18, roos2022sixgenerationsof pages 1-9).
- Neuronal cell biology: CHMP2B T104N mutation shifts localization to Golgi aggregates and impairs neurite outgrowth; D148Y similarly perturbs Golgi stress signaling and morphology, with rescue by Hsp47/Arf4 modulation (Aug 2023; Feb 2024) (shirai2023ftdalstype7associated pages 4-6, fukatsu2024modulatinggolgistress pages 1-2).

10) Verification of identity and domain alignment
- All cited sources explicitly refer to human CHMP2B, an ESCRT‑III/SNF7 family protein operating in the endolysosomal and membrane scission pathways; no evidence was found for conflicting gene symbols/organisms. These align with the UniProt record (Q9UQN3; Homo sapiens; SNF7 family) provided in the prompt (Nucleus, 2024; Human Molecular Genetics, 2020) (keeley2024nuclearanddegradative pages 1-3, fortaznar2020retrovirusreactivationin pages 14-15).

Notes on scope and limitations
- Some mechanistic details (e.g., direct structural data specific to human CHMP2B polymers) are better established for other ESCRT‑III subunits; where needed we referenced authoritative reviews integrating ESCRT‑III assembly mechanisms that include CHMP2B’s role. The 2023–2024 primary advances most directly specific to CHMP2B include K6 methylation (SMYD2) and new mutation‑linked neuronal phenotypes and subcellular mislocalization (T104N, D148Y), plus biomarker and natural‑history data in the Danish pedigree (richard2024methylationofescrtiii pages 1-2, shirai2023ftdalstype7associated pages 4-6, fukatsu2024modulatinggolgistress pages 1-2, toft2023endo‐lysosomalproteinconcentrations pages 1-2, roos2022sixgenerationsof pages 9-13).

References (URLs and dates)
- Keeley O, Coyne AN. Nuclear and degradative functions of the ESCRT‑III pathway: implications for neurodegenerative disease. Nucleus. May 2024. https://doi.org/10.1080/19491034.2024.2349085 (keeley2024nuclearanddegradative pages 1-3, keeley2024nuclearanddegradative pages 9-10).
- Richard A, et al. Methylation of ESCRT‑III components regulates the timing of cytokinetic abscission. Nature Communications. May 2024. https://doi.org/10.1038/s41467-024-47717-3 (richard2024methylationofescrtiii pages 1-2).
- Li C, et al. A novel splice‑site mutation in CHMP2B associated with frontotemporal dementia: The first report from China and literature review. Mol Genet Genomic Med. Jun 2023. https://doi.org/10.1002/mgg3.2222 (li2023anovelsplice‐site pages 3-4).
- Shirai R, et al. FTD/ALS7‑associated Thr104Asn mutation of CHMP2B blunts neuronal process elongation… Neurology International. Aug 2023. https://doi.org/10.3390/neurolint15030063 (shirai2023ftdalstype7associated pages 4-6).
- Fukatsu S, et al. Modulating Golgi Stress Signaling Ameliorates… CHMP2B p.Asp148Tyr. Current Issues in Molecular Biology. Feb 2024. https://doi.org/10.3390/cimb46020090 (fukatsu2024modulatinggolgistress pages 1-2).
- Toft A, et al. Endo‑lysosomal protein concentrations in CSF from patients with FTD caused by CHMP2B mutation. Alzheimer’s & Dementia: DADM. Jan 2023. https://doi.org/10.1002/dad2.12402 (toft2023endo‐lysosomalproteinconcentrations pages 1-2, toft2023endo‐lysosomalproteinconcentrations pages 5-6, toft2023endo‐lysosomalproteinconcentrations pages 2-3, toft2023endo‐lysosomalproteinconcentrations pages 6-7).
- Roos P, et al. Six generations of CHMP2B‑mediated Frontotemporal Dementia: clinical features, progression, and survival. Acta Neurol Scand. Jan 2022. https://doi.org/10.1111/ane.13578 (roos2022sixgenerationsof pages 9-13, roos2022sixgenerationsof pages 13-18, roos2022sixgenerationsof pages 1-9).
- Fort‑Aznar L, Ugbode C, Sweeney ST. Retrovirus reactivation in CHMP2BIntron5 models of FTD. Hum Mol Genet. Jul 2020. https://doi.org/10.1093/hmg/ddaa142 (fortaznar2020retrovirusreactivationin pages 14-15).

References

(keeley2024nuclearanddegradative pages 1-3): Olivia Keeley and Alyssa N. Coyne. Nuclear and degradative functions of the escrt-iii pathway: implications for neurodegenerative disease. Nucleus, May 2024. URL: https://doi.org/10.1080/19491034.2024.2349085, doi:10.1080/19491034.2024.2349085. This article has 12 citations and is from a peer-reviewed journal.
(richard2024methylationofescrtiii pages 1-2): Aurélie Richard, Jérémy Berthelet, Delphine Judith, Tamara Advedissian, Javier Espadas, Guillaume Jannot, Angélique Amo, Damarys Loew, Berangere Lombard, Alexandre G. Casanova, Nicolas Reynoird, Aurélien Roux, Clarisse Berlioz-Torrent, Arnaud Echard, Jonathan B. Weitzman, and Souhila Medjkane. Methylation of escrt-iii components regulates the timing of cytokinetic abscission. Nature Communications, May 2024. URL: https://doi.org/10.1038/s41467-024-47717-3, doi:10.1038/s41467-024-47717-3. This article has 6 citations and is from a highest quality peer-reviewed journal.
(keeley2024nuclearanddegradative pages 9-10): Olivia Keeley and Alyssa N. Coyne. Nuclear and degradative functions of the escrt-iii pathway: implications for neurodegenerative disease. Nucleus, May 2024. URL: https://doi.org/10.1080/19491034.2024.2349085, doi:10.1080/19491034.2024.2349085. This article has 12 citations and is from a peer-reviewed journal.
(li2023anovelsplice‐site pages 3-4): Chang Li, Ya Wen, Mengqiu Zhao, Yaye Wang, Ping Li, Liang Wang, and Shan Wang. A novel splice‐site mutation in chmp2b associated with frontotemporal dementia: the first report from china and literature review. Molecular Genetics & Genomic Medicine, Jun 2023. URL: https://doi.org/10.1002/mgg3.2222, doi:10.1002/mgg3.2222. This article has 2 citations and is from a peer-reviewed journal.
(shirai2023ftdalstype7associated pages 4-6): Remina Shirai, Mizuka Cho, Mikinori Isogai, Shoya Fukatsu, Miyu Okabe, Maho Okawa, Yuki Miyamoto, Tomohiro Torii, and Junji Yamauchi. Ftd/als type 7-associated thr104asn mutation of chmp2b blunts neuronal process elongation, and is recovered by knockdown of arf4, the golgi stress regulator. Neurology International, 15:980-993, Aug 2023. URL: https://doi.org/10.3390/neurolint15030063, doi:10.3390/neurolint15030063. This article has 5 citations and is from a poor quality or predatory journal.
(fukatsu2024modulatinggolgistress pages 1-2): Shoya Fukatsu, Maho Okawa, Miyu Okabe, Mizuka Cho, Mikinori Isogai, Takanori Yokoi, Remina Shirai, Hiroaki Oizumi, Masahiro Yamamoto, Katsuya Ohbuchi, Yuki Miyamoto, and Junji Yamauchi. Modulating golgi stress signaling ameliorates cell morphological phenotypes induced by chmp2b with frontotemporal dementia-associated p.asp148tyr. Current Issues in Molecular Biology, 46:1398-1412, Feb 2024. URL: https://doi.org/10.3390/cimb46020090, doi:10.3390/cimb46020090. This article has 0 citations and is from a poor quality or predatory journal.
(toft2023endo‐lysosomalproteinconcentrations pages 1-2): Anders Toft, Simon Sjödin, Anja Hviid Simonsen, Patrick Ejlerskov, Peter Roos, Christian Sandøe Musaeus, Emil Elbæk Henriksen, Troels Tolstrup Nielsen, Ann Brinkmalm, Kaj Blennow, Henrik Zetterberg, and Jørgen Erik Nielsen. Endo‐lysosomal protein concentrations in csf from patients with frontotemporal dementia caused by chmp2b mutation. Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring, Jan 2023. URL: https://doi.org/10.1002/dad2.12402, doi:10.1002/dad2.12402. This article has 3 citations and is from a peer-reviewed journal.
(toft2023endo‐lysosomalproteinconcentrations pages 5-6): Anders Toft, Simon Sjödin, Anja Hviid Simonsen, Patrick Ejlerskov, Peter Roos, Christian Sandøe Musaeus, Emil Elbæk Henriksen, Troels Tolstrup Nielsen, Ann Brinkmalm, Kaj Blennow, Henrik Zetterberg, and Jørgen Erik Nielsen. Endo‐lysosomal protein concentrations in csf from patients with frontotemporal dementia caused by chmp2b mutation. Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring, Jan 2023. URL: https://doi.org/10.1002/dad2.12402, doi:10.1002/dad2.12402. This article has 3 citations and is from a peer-reviewed journal.
(toft2023endo‐lysosomalproteinconcentrations pages 2-3): Anders Toft, Simon Sjödin, Anja Hviid Simonsen, Patrick Ejlerskov, Peter Roos, Christian Sandøe Musaeus, Emil Elbæk Henriksen, Troels Tolstrup Nielsen, Ann Brinkmalm, Kaj Blennow, Henrik Zetterberg, and Jørgen Erik Nielsen. Endo‐lysosomal protein concentrations in csf from patients with frontotemporal dementia caused by chmp2b mutation. Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring, Jan 2023. URL: https://doi.org/10.1002/dad2.12402, doi:10.1002/dad2.12402. This article has 3 citations and is from a peer-reviewed journal.
(toft2023endo‐lysosomalproteinconcentrations pages 6-7): Anders Toft, Simon Sjödin, Anja Hviid Simonsen, Patrick Ejlerskov, Peter Roos, Christian Sandøe Musaeus, Emil Elbæk Henriksen, Troels Tolstrup Nielsen, Ann Brinkmalm, Kaj Blennow, Henrik Zetterberg, and Jørgen Erik Nielsen. Endo‐lysosomal protein concentrations in csf from patients with frontotemporal dementia caused by chmp2b mutation. Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring, Jan 2023. URL: https://doi.org/10.1002/dad2.12402, doi:10.1002/dad2.12402. This article has 3 citations and is from a peer-reviewed journal.
(roos2022sixgenerationsof pages 9-13): Peter Roos, Peter Johannsen, Suzanne G. Lindquist, Jeremy M. Brown, Gunhild Waldemar, Morten Duno, Troels T. Nielsen, Esben Budtz‐Jørgensen, Susanne Gydesen, Ida E. Holm, John Collinge, Adrian M. Isaacs, Jørgen E. Nielsen, Anders Gade, Jette Stokholm, Tove Thusgaard, Elizabeth M.C. Fisher, and Elisabet Englund. Six generations of chmp2b‐mediated frontotemporal dementia: clinical features, predictive testing, progression, and survival. Acta Neurologica Scandinavica, 145:529-540, Jan 2022. URL: https://doi.org/10.1111/ane.13578, doi:10.1111/ane.13578. This article has 8 citations and is from a peer-reviewed journal.
(roos2022sixgenerationsof pages 13-18): Peter Roos, Peter Johannsen, Suzanne G. Lindquist, Jeremy M. Brown, Gunhild Waldemar, Morten Duno, Troels T. Nielsen, Esben Budtz‐Jørgensen, Susanne Gydesen, Ida E. Holm, John Collinge, Adrian M. Isaacs, Jørgen E. Nielsen, Anders Gade, Jette Stokholm, Tove Thusgaard, Elizabeth M.C. Fisher, and Elisabet Englund. Six generations of chmp2b‐mediated frontotemporal dementia: clinical features, predictive testing, progression, and survival. Acta Neurologica Scandinavica, 145:529-540, Jan 2022. URL: https://doi.org/10.1111/ane.13578, doi:10.1111/ane.13578. This article has 8 citations and is from a peer-reviewed journal.
(roos2022sixgenerationsof pages 1-9): Peter Roos, Peter Johannsen, Suzanne G. Lindquist, Jeremy M. Brown, Gunhild Waldemar, Morten Duno, Troels T. Nielsen, Esben Budtz‐Jørgensen, Susanne Gydesen, Ida E. Holm, John Collinge, Adrian M. Isaacs, Jørgen E. Nielsen, Anders Gade, Jette Stokholm, Tove Thusgaard, Elizabeth M.C. Fisher, and Elisabet Englund. Six generations of chmp2b‐mediated frontotemporal dementia: clinical features, predictive testing, progression, and survival. Acta Neurologica Scandinavica, 145:529-540, Jan 2022. URL: https://doi.org/10.1111/ane.13578, doi:10.1111/ane.13578. This article has 8 citations and is from a peer-reviewed journal.
(musaeus2021corticalfrontoparietalnetwork pages 1-2): C. Musaeus, J. S. Pedersen, T. Kjær, P. Johannsen, G. Waldemar, Maria Joy Normann Haverberg, T. Bacher, J. Nielsen, P. Roos, and S J AM J A E E TT T I Gydesen Brown Isaacs Collinge Gade Englund Fisher. Cortical frontoparietal network dysfunction in chmp2b-frontotemporal dementia. Frontiers in Aging Neuroscience, Sep 2021. URL: https://doi.org/10.3389/fnagi.2021.714220, doi:10.3389/fnagi.2021.714220. This article has 6 citations and is from a peer-reviewed journal.
(fortaznar2020retrovirusreactivationin pages 14-15): Laura Fort-Aznar, Chris Ugbode, and Sean T Sweeney. Retrovirus reactivation in chmp2bintron5 models of frontotemporal dementia. Human Molecular Genetics, 29:2637-2646, Jul 2020. URL: https://doi.org/10.1093/hmg/ddaa142, doi:10.1093/hmg/ddaa142. This article has 10 citations and is from a domain leading peer-reviewed journal.

Citations

keeley2024nuclearanddegradative pages 1-3
richard2024methylationofescrtiii pages 1-2
keeley2024nuclearanddegradative pages 9-10
fukatsu2024modulatinggolgistress pages 1-2
musaeus2021corticalfrontoparietalnetwork pages 1-2
fortaznar2020retrovirusreactivationin pages 14-15
roos2022sixgenerationsof pages 9-13
roos2022sixgenerationsof pages 13-18
roos2022sixgenerationsof pages 1-9
https://doi.org/10.1038/s41467-024-47717-3
https://doi.org/10.1080/19491034.2024.2349085
https://doi.org/10.1002/mgg3.2222
https://doi.org/10.3390/neurolint15030063
https://doi.org/10.3390/cimb46020090
https://doi.org/10.1002/dad2.12402
https://doi.org/10.1111/ane.13578
https://doi.org/10.3389/fnagi.2021.714220
https://doi.org/10.1038/s41580-024-00757-5
https://doi.org/10.1093/hmg/ddaa142
https://doi.org/10.1080/19491034.2024.2349085,
https://doi.org/10.1038/s41467-024-47717-3,
https://doi.org/10.1002/mgg3.2222,
https://doi.org/10.3390/neurolint15030063,
https://doi.org/10.3390/cimb46020090,
https://doi.org/10.1002/dad2.12402,
https://doi.org/10.1111/ane.13578,
https://doi.org/10.3389/fnagi.2021.714220,
https://doi.org/10.1093/hmg/ddaa142,

📄 View Raw YAML

---
id: Q9UQN3
gene_symbol: CHMP2B
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: CHMP2B (Charged multivesicular body protein 2b) is a core component of
  the ESCRT-III (Endosomal Sorting Complex Required for Transport III) machinery,
  belonging to the evolutionarily conserved SNF7 family. CHMP2B functions as a structural
  subunit that assembles into helical polymers on membranes to mediate reverse-topology
  membrane scission events. The protein participates in multiple cellular processes
  including multivesicular body (MVB) formation and cargo sorting, cytokinetic abscission
  at the midbody, nuclear envelope reformation during telophase, plasma membrane repair,
  autophagosome maturation, and viral budding (particularly HIV-1). CHMP2B is recruited
  to membrane necks where it cooperates with other ESCRT-III subunits (CHMP4B, CHMP3)
  and the AAA ATPase VPS4 for membrane remodeling and fission. Mutations in CHMP2B
  cause frontotemporal dementia and/or amyotrophic lateral sclerosis (FTDALS7), demonstrating
  the critical importance of ESCRT-III function in neuronal homeostasis. The protein
  contains an N-terminal MIT-interacting motif that mediates interaction with VPS4,
  and post-translational modifications including K6 methylation by SMYD2 regulate
  its polymerization dynamics and abscission timing.
existing_annotations:
  - term:
      id: GO:0005771
      label: multivesicular body
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: CHMP2B is a core ESCRT-III subunit with well-established localization
        to multivesicular bodies. This is supported by phylogenetic conservation across
        eukaryotes and extensive experimental evidence showing CHMP2B at MVB membranes
        (PMID:16554368, PMID:16041373).
      action: ACCEPT
      reason: Core localization for ESCRT-III function. CHMP2B localizes to MVB membranes
        where it participates in intraluminal vesicle formation. The IBA annotation
        is well-supported by the phylogenetic analysis and corroborated by multiple
        IDA annotations.
      supported_by:
        - reference_id: file:human/CHMP2B/CHMP2B-deep-research-falcon.md
          supporting_text: 'model: Edison Scientific Literature'
  - term:
      id: GO:0015031
      label: protein transport
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: CHMP2B participates in protein transport through its role in the MVB
        pathway, which sorts ubiquitinated membrane proteins for lysosomal degradation.
      action: ACCEPT
      reason: The MVB pathway is fundamentally a protein transport pathway, sorting
        ubiquitinated cargo into intraluminal vesicles for subsequent lysosomal degradation.
        This is a core function of ESCRT-III components including CHMP2B.
  - term:
      id: GO:0032509
      label: endosome transport via multivesicular body sorting pathway
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: CHMP2B is essential for the MVB sorting pathway, mediating endosomal
        cargo transport through its role in intraluminal vesicle formation.
      action: ACCEPT
      reason: This is a core function of CHMP2B as an ESCRT-III subunit. The protein
        is required for the proper formation of intraluminal vesicles within MVBs,
        enabling cargo sorting and transport.
  - term:
      id: GO:0045324
      label: late endosome to vacuole transport
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: CHMP2B participates in transport from late endosomes to lysosomes (the
        mammalian equivalent of vacuoles) through its role in MVB biogenesis and fusion.
      action: ACCEPT
      reason: This represents the conserved ESCRT-III function in endolysosomal transport.
        The term is appropriate for the mammalian system where lysosomes serve the
        function of yeast vacuoles.
  - term:
      id: GO:0000815
      label: ESCRT III complex
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: CHMP2B is a bona fide subunit of the ESCRT-III complex, confirmed by
        both phylogenetic analysis and direct biochemical evidence.
      action: ACCEPT
      reason: CHMP2B is a core ESCRT-III subunit belonging to the SNF7 family. Its
        membership in the complex is unequivocally established through structural,
        biochemical, and functional studies.
  - term:
      id: GO:0000776
      label: kinetochore
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: ESCRT-III components including CHMP2B have been shown to localize to
        kinetochores during mitosis, supported by IDA evidence from PMID:26040712.
      action: ACCEPT
      reason: This IEA annotation is corroborated by direct experimental evidence
        (IDA from PMID:26040712). CHMP2B localizes to kinetochores as part of its
        mitotic functions in spindle maintenance and chromosome segregation.
  - term:
      id: GO:0001778
      label: plasma membrane repair
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: ESCRT-III machinery is required for plasma membrane repair, supported
        by IDA evidence from PMID:24482116.
      action: ACCEPT
      reason: This IEA annotation is validated by direct experimental evidence. The
        ESCRT machinery performs membrane sealing functions during plasma membrane
        repair, analogous to its role in other membrane fission events.
  - term:
      id: GO:0005643
      label: nuclear pore
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHMP2B has been detected at nuclear pores as part of ESCRT-III function
        in nuclear envelope reformation, though its primary localization is at sites
        of annular fusion rather than mature nuclear pores.
      action: KEEP_AS_NON_CORE
      reason: CHMP2B localizes to nucleo-cytoplasmic channels during nuclear envelope
        reformation (PMID:26040713), which are precursors to nuclear pore formation.
        However, it is not a stable component of mature nuclear pore complexes. This
        is a transient localization related to its membrane sealing function.
  - term:
      id: GO:0005765
      label: lysosomal membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHMP2B localizes to lysosomal membranes as part of the endolysosomal
        pathway, supported by IDA evidence from PMID:17984323.
      action: ACCEPT
      reason: The annotation is supported by direct experimental evidence showing
        CHMP2B localization to lysosomal membranes in the context of autophagy and
        MVB-lysosome fusion.
  - term:
      id: GO:0005828
      label: kinetochore microtubule
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: ESCRT-III components localize to kinetochore microtubules during mitosis,
        supported by IDA evidence from PMID:26040712.
      action: ACCEPT
      reason: This annotation is validated by direct experimental evidence showing
        ESCRT-III localization at spindle poles and kinetochore microtubules.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: CHMP2B is present in the cytosol in its soluble, inactive form before
        recruitment to membranes.
      action: ACCEPT
      reason: ESCRT-III proteins exist in an autoinhibited soluble form in the cytosol
        and are recruited to membranes upon activation. This is well-established for
        CHMP2B.
  - term:
      id: GO:0007034
      label: vacuolar transport
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: InterPro-based annotation reflecting CHMP2B's role in vacuolar/lysosomal
        transport as an ESCRT-III subunit.
      action: ACCEPT
      reason: The SNF7 domain annotation appropriately maps to vacuolar transport
        function. In mammalian cells, this corresponds to lysosomal transport pathways.
  - term:
      id: GO:0007080
      label: mitotic metaphase chromosome alignment
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: ESCRT-III depletion affects chromosome alignment during mitosis, supported
        by IMP evidence from PMID:20616062.
      action: KEEP_AS_NON_CORE
      reason: While CHMP2B depletion does affect chromosome alignment (PMID:20616062),
        this represents a secondary consequence of centrosome/spindle defects rather
        than a direct function. The core ESCRT-III function is membrane remodeling.
  - term:
      id: GO:0015031
      label: protein transport
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: UniProt keyword-based annotation for protein transport, reflecting
        CHMP2B's role in sorting and trafficking.
      action: ACCEPT
      reason: Appropriately broad annotation that captures CHMP2B's role in protein
        sorting through the MVB pathway. Duplicates the IBA annotation but from a
        different source.
  - term:
      id: GO:0030496
      label: midbody
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHMP2B localizes to the midbody during cytokinesis, supported by IDA
        evidence from PMID:26040712.
      action: ACCEPT
      reason: Midbody localization is a core feature of ESCRT-III function in cytokinetic
        abscission. Well-validated by direct experimental evidence.
  - term:
      id: GO:0031468
      label: nuclear membrane reassembly
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHMP2B participates in nuclear envelope reformation during telophase,
        supported by IMP evidence from PMID:26040713.
      action: ACCEPT
      reason: This is a validated core function of ESCRT-III. The complex is recruited
        to sites of annular fusion during nuclear envelope reformation.
  - term:
      id: GO:0031902
      label: late endosome membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: CHMP2B localizes to late endosome membranes as part of the MVB pathway.
      action: ACCEPT
      reason: Core localization for ESCRT-III function in MVB biogenesis. Late endosomes
        are the site of intraluminal vesicle formation.
  - term:
      id: GO:0032585
      label: multivesicular body membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHMP2B localizes to MVB membranes, supported by IDA evidence from PMID:16554368.
      action: ACCEPT
      reason: Core localization for ESCRT-III function. This is the primary site where
        CHMP2B functions in intraluminal vesicle formation.
  - term:
      id: GO:0039702
      label: viral budding via host ESCRT complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHMP2B participates in viral budding processes, particularly for HIV-1,
        supported by IDA evidence from PMID:24878737 and IMP from PMID:23051622.
      action: ACCEPT
      reason: This is a well-established function of ESCRT-III. The complex is hijacked
        by retroviruses for viral budding, which is topologically equivalent to MVB
        intraluminal vesicle formation.
  - term:
      id: GO:0043162
      label: ubiquitin-dependent protein catabolic process via the multivesicular
        body sorting pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHMP2B is essential for MVB-mediated degradation of ubiquitinated cargo
        proteins, supported by IDA evidence from PMID:17984323.
      action: ACCEPT
      reason: Core function of the ESCRT pathway. CHMP2B is required for proper sorting
        and degradation of ubiquitinated membrane proteins through the MVB pathway.
  - term:
      id: GO:0046761
      label: viral budding from plasma membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHMP2B participates in viral budding from the plasma membrane, supported
        by IDA evidence from PMID:24878737.
      action: ACCEPT
      reason: HIV-1 and other enveloped viruses bud from the plasma membrane using
        ESCRT machinery. This is a validated function for ESCRT-III components.
  - term:
      id: GO:0061952
      label: midbody abscission
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHMP2B is required for the final abscission step of cytokinesis, supported
        by IMP evidence from PMID:20616062.
      action: ACCEPT
      reason: Core function of ESCRT-III. The complex mediates membrane fission at
        the midbody to complete cell division.
  - term:
      id: GO:0071985
      label: multivesicular body sorting pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHMP2B is essential for the MVB sorting pathway, supported by IDA evidence
        from PMID:16554368.
      action: ACCEPT
      reason: This is the primary biological process in which CHMP2B functions as
        an ESCRT-III subunit.
  - term:
      id: GO:0097352
      label: autophagosome maturation
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHMP2B is required for autophagosome maturation, supported by IMP evidence
        from PMID:17984323.
      action: ACCEPT
      reason: The ESCRT machinery is required for phagophore closure and autophagosome-
        lysosome fusion. CHMP2B mutations cause defects in autophagy.
  - term:
      id: GO:1901673
      label: regulation of mitotic spindle assembly
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: ESCRT-III depletion affects spindle assembly, supported by IMP evidence
        from PMID:20616062.
      action: KEEP_AS_NON_CORE
      reason: While CHMP2B depletion does affect spindle assembly (PMID:20616062),
        this is likely a secondary effect of centrosome defects rather than a direct
        regulatory function.
  - term:
      id: GO:1902774
      label: late endosome to lysosome transport
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHMP2B is required for late endosome to lysosome transport, supported
        by IMP evidence from PMID:17984323.
      action: ACCEPT
      reason: Core function of ESCRT-III in the endolysosomal pathway. MVB-lysosome
        fusion requires functional ESCRT machinery.
  - term:
      id: GO:1904930
      label: amphisome membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHMP2B localizes to amphisome membranes, supported by IDA evidence
        from PMID:17984323.
      action: ACCEPT
      reason: Amphisomes are intermediates between autophagosomes and lysosomes. ESCRT
        depletion causes accumulation of amphisomes, indicating CHMP2B function at
        this compartment.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16730941
    review:
      summary: CHMP2B interacts with CHMP3 (PMID:16730941). While protein binding
        is too general, this reflects specific ESCRT-III complex assembly.
      action: MARK_AS_OVER_ANNOTATED
      reason: Protein binding is not informative. The specific interaction with CHMP3
        would be better captured as ESCRT-III complex assembly function.
      proposed_replacement_terms:
        - id: GO:0000815
          label: ESCRT III complex
      supported_by:
        - reference_id: PMID:16730941
          supporting_text: 'May 30. A systematic analysis of human CHMP protein interactions:
            additional MIT domain-containing proteins bind to multiple components
            of the human ESCRT III complex.'
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21044950
    review:
      summary: CHMP2B interacts with TERF2IP in a YFP fluorescence complementation
        screen for telomere signaling regulators.
      action: MARK_AS_OVER_ANNOTATED
      reason: Protein binding is not informative. This appears to be a high-throughput
        screen result without clear functional significance for CHMP2B.
      supported_by:
        - reference_id: PMID:21044950
          supporting_text: Epub 2010 Nov 2. Genome-wide YFP fluorescence complementation
            screen identifies new regulators for telomere signaling in human cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:22046132
    review:
      summary: CHMP2B interacts with viral Rep proteins based on IntAct data.
      action: MARK_AS_OVER_ANNOTATED
      reason: Protein binding is not informative. The viral interaction would be better
        described in the context of viral budding function.
      supported_by:
        - reference_id: PMID:22046132
          supporting_text: '2011 Oct 27. The SARS-coronavirus-host interactome: identification
            of cyclophilins as target for pan-coronavirus inhibitors.'
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23051622
    review:
      summary: CHMP2B interacts with CHMP4B and CHMP3 as part of ESCRT-III assembly
        during HIV-1 budding.
      action: MARK_AS_OVER_ANNOTATED
      reason: Protein binding is not informative. These interactions reflect ESCRT-III
        complex assembly, better captured by complex membership annotation.
      supported_by:
        - reference_id: PMID:23051622
          supporting_text: ESCRT-III CHMP2A and CHMP3 form variable helical polymers
            in vitro and act synergistically during HIV-1 budding.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:26496610
    review:
      summary: CHMP2B interacts with CHMP4B in stoichiometry studies.
      action: MARK_AS_OVER_ANNOTATED
      reason: Protein binding is not informative. Better captured by ESCRT-III complex
        membership.
      supported_by:
        - reference_id: PMID:26496610
          supporting_text: Oct 22. A human interactome in three quantitative dimensions
            organized by stoichiometries and abundances.
  - term:
      id: GO:0000421
      label: autophagosome membrane
    evidence_type: IDA
    original_reference_id: PMID:17984323
    review:
      summary: CHMP2B localizes to autophagosome membranes based on direct observation
        in cells expressing CHMP2B mutants and controls.
      action: ACCEPT
      reason: This localization is functionally relevant as ESCRT machinery is required
        for phagophore closure during autophagosome formation.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: Functional multivesicular bodies are required for autophagic
            clearance of protein aggregates associated with neurodegenerative disease.
  - term:
      id: GO:0000776
      label: kinetochore
    evidence_type: IDA
    original_reference_id: PMID:26040712
    review:
      summary: ESCRT-III components localize to kinetochores during mitosis based
        on immunofluorescence.
      action: ACCEPT
      reason: Validated localization that supports the mitotic functions of ESCRT-III.
      supported_by:
        - reference_id: PMID:26040712
          supporting_text: Spastin and ESCRT-III coordinate mitotic spindle disassembly
            and nuclear envelope sealing.
  - term:
      id: GO:0001778
      label: plasma membrane repair
    evidence_type: IDA
    original_reference_id: PMID:24482116
    review:
      summary: The ESCRT machinery is required for plasma membrane repair based on
        functional studies.
      action: ACCEPT
      reason: ESCRT-III mediates membrane sealing during plasma membrane repair, analogous
        to its function in other membrane fission events.
      supported_by:
        - reference_id: PMID:24482116
          supporting_text: 2014 Jan 30. ESCRT machinery is required for plasma membrane
            repair.
  - term:
      id: GO:0005765
      label: lysosomal membrane
    evidence_type: IDA
    original_reference_id: PMID:17984323
    review:
      summary: CHMP2B localizes to lysosomal membranes in the context of autophagy
        and MVB-lysosome fusion.
      action: ACCEPT
      reason: Functional localization supporting ESCRT role in endolysosomal trafficking.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: Functional multivesicular bodies are required for autophagic
            clearance of protein aggregates associated with neurodegenerative disease.
  - term:
      id: GO:0005828
      label: kinetochore microtubule
    evidence_type: IDA
    original_reference_id: PMID:26040712
    review:
      summary: ESCRT-III components localize to kinetochore microtubules during mitosis.
      action: ACCEPT
      reason: This localization supports ESCRT-III function in spindle maintenance.
      supported_by:
        - reference_id: PMID:26040712
          supporting_text: Spastin and ESCRT-III coordinate mitotic spindle disassembly
            and nuclear envelope sealing.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: IDA
    original_reference_id: PMID:24878737
    review:
      summary: CHMP2B localizes to the plasma membrane during viral budding and membrane
        repair processes.
      action: ACCEPT
      reason: Functional localization for ESCRT-III in plasma membrane fission events.
      supported_by:
        - reference_id: PMID:24878737
          supporting_text: Structure of cellular ESCRT-III spirals and their relationship
            to HIV budding.
  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: IMP
    original_reference_id: PMID:17984323
    review:
      summary: CHMP2B is required for autophagy based on mutant phenotype analysis.
        CHMP2B mutants cause accumulation of autophagic compartments and protein aggregates.
      action: ACCEPT
      reason: This is a core function demonstrated by disease-causing mutations. ESCRT-III
        is required for autophagosome closure and amphisome-lysosome fusion.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: Functional multivesicular bodies are required for autophagic
            clearance of protein aggregates associated with neurodegenerative disease.
  - term:
      id: GO:0006997
      label: nucleus organization
    evidence_type: IMP
    original_reference_id: PMID:20616062
    review:
      summary: ESCRT-III depletion causes nuclear morphology defects.
      action: KEEP_AS_NON_CORE
      reason: This is a secondary consequence of defects in nuclear envelope reformation
        and spindle function rather than a primary regulatory role in nucleus organization.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: Human ESCRT-III and VPS4 proteins are required for centrosome
            and spindle maintenance.
  - term:
      id: GO:0007080
      label: mitotic metaphase chromosome alignment
    evidence_type: IMP
    original_reference_id: PMID:20616062
    review:
      summary: ESCRT-III depletion affects chromosome alignment during mitosis.
      action: KEEP_AS_NON_CORE
      reason: This is a secondary consequence of centrosome/spindle defects rather
        than a direct function in chromosome alignment.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: Human ESCRT-III and VPS4 proteins are required for centrosome
            and spindle maintenance.
  - term:
      id: GO:0030496
      label: midbody
    evidence_type: IDA
    original_reference_id: PMID:26040712
    review:
      summary: ESCRT-III components localize to the midbody during cytokinesis based
        on immunofluorescence.
      action: ACCEPT
      reason: Core localization for ESCRT-III function in cytokinetic abscission.
      supported_by:
        - reference_id: PMID:26040712
          supporting_text: Spastin and ESCRT-III coordinate mitotic spindle disassembly
            and nuclear envelope sealing.
  - term:
      id: GO:0031468
      label: nuclear membrane reassembly
    evidence_type: IMP
    original_reference_id: PMID:26040713
    review:
      summary: CHMP2B is required for nuclear envelope reformation based on functional
        depletion studies.
      action: ACCEPT
      reason: Core function of ESCRT-III in sealing the nuclear envelope during telophase.
        Well-validated by two independent studies.
      supported_by:
        - reference_id: PMID:26040713
          supporting_text: ESCRT-III controls nuclear envelope reformation.
  - term:
      id: GO:0032585
      label: multivesicular body membrane
    evidence_type: IDA
    original_reference_id: PMID:16554368
    review:
      summary: CHMP2B localizes to MVB membranes based on immunofluorescence and functional
        studies.
      action: ACCEPT
      reason: Core localization for ESCRT-III function in MVB biogenesis.
      supported_by:
        - reference_id: PMID:16554368
          supporting_text: Mar 22. The ESCRT-III subunit hVps24 is required for degradation
            but not silencing of the epidermal growth factor receptor.
  - term:
      id: GO:0036258
      label: multivesicular body assembly
    evidence_type: NAS
    original_reference_id: PMID:16505166
    review:
      summary: CHMP2B participates in MVB assembly as an ESCRT-III subunit.
      action: ACCEPT
      reason: Core function of ESCRT-III. Well-established through multiple lines
        of evidence.
      supported_by:
        - reference_id: PMID:16505166
          supporting_text: Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated
            by a conserved VSL region in Vta1.
  - term:
      id: GO:0039702
      label: viral budding via host ESCRT complex
    evidence_type: IDA
    original_reference_id: PMID:24878737
    review:
      summary: CHMP2B is directly visualized forming spirals during HIV budding.
      action: ACCEPT
      reason: Direct structural evidence for ESCRT-III function in viral budding.
      supported_by:
        - reference_id: PMID:24878737
          supporting_text: Structure of cellular ESCRT-III spirals and their relationship
            to HIV budding.
  - term:
      id: GO:0043162
      label: ubiquitin-dependent protein catabolic process via the multivesicular
        body sorting pathway
    evidence_type: IDA
    original_reference_id: PMID:17984323
    review:
      summary: CHMP2B is required for MVB-mediated degradation of ubiquitinated proteins
        based on direct demonstration of cargo accumulation.
      action: ACCEPT
      reason: Core function of ESCRT pathway. CHMP2B is essential for sorting ubiquitinated
        cargo into MVBs for degradation.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: Functional multivesicular bodies are required for autophagic
            clearance of protein aggregates associated with neurodegenerative disease.
  - term:
      id: GO:0046761
      label: viral budding from plasma membrane
    evidence_type: IDA
    original_reference_id: PMID:24878737
    review:
      summary: CHMP2B forms spirals at the plasma membrane during viral budding.
      action: ACCEPT
      reason: Direct visualization of ESCRT-III at budding sites on plasma membrane.
      supported_by:
        - reference_id: PMID:24878737
          supporting_text: Structure of cellular ESCRT-III spirals and their relationship
            to HIV budding.
  - term:
      id: GO:0051469
      label: vesicle fusion with vacuole
    evidence_type: NAS
    original_reference_id: PMID:16505166
    review:
      summary: CHMP2B participates in MVB-lysosome fusion (mammalian equivalent of
        vesicle-vacuole fusion).
      action: MODIFY
      reason: In mammalian cells, this process is MVB-lysosome fusion. The term is
        more appropriate for yeast.
      proposed_replacement_terms:
        - id: GO:0061763
          label: multivesicular body-lysosome fusion
      supported_by:
        - reference_id: PMID:16505166
          supporting_text: Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated
            by a conserved VSL region in Vta1.
  - term:
      id: GO:0061763
      label: multivesicular body-lysosome fusion
    evidence_type: NAS
    original_reference_id: PMID:16505166
    review:
      summary: CHMP2B participates in MVB-lysosome fusion as an ESCRT-III subunit.
      action: ACCEPT
      reason: ESCRT-III function is required for efficient MVB-lysosome fusion.
      supported_by:
        - reference_id: PMID:16505166
          supporting_text: Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated
            by a conserved VSL region in Vta1.
  - term:
      id: GO:0061952
      label: midbody abscission
    evidence_type: IMP
    original_reference_id: PMID:20616062
    review:
      summary: CHMP2B is required for cytokinetic abscission based on depletion phenotype.
      action: ACCEPT
      reason: Core function of ESCRT-III. The complex mediates the final membrane
        fission step of cytokinesis.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: Human ESCRT-III and VPS4 proteins are required for centrosome
            and spindle maintenance.
  - term:
      id: GO:0071985
      label: multivesicular body sorting pathway
    evidence_type: IDA
    original_reference_id: PMID:16554368
    review:
      summary: CHMP2B is essential for MVB sorting pathway function.
      action: ACCEPT
      reason: Primary biological process for ESCRT-III function.
      supported_by:
        - reference_id: PMID:16554368
          supporting_text: Mar 22. The ESCRT-III subunit hVps24 is required for degradation
            but not silencing of the epidermal growth factor receptor.
  - term:
      id: GO:0090148
      label: membrane fission
    evidence_type: NAS
    original_reference_id: PMID:19234443
    review:
      summary: ESCRT-III directly mediates membrane fission based on reconstitution
        studies.
      action: ACCEPT
      reason: Core molecular function of ESCRT-III. The complex drives membrane scission
        in multiple contexts.
      supported_by:
        - reference_id: PMID:19234443
          supporting_text: Membrane scission by the ESCRT-III complex.
  - term:
      id: GO:0097352
      label: autophagosome maturation
    evidence_type: IMP
    original_reference_id: PMID:17984323
    review:
      summary: CHMP2B is required for autophagosome maturation based on mutant phenotype.
      action: ACCEPT
      reason: ESCRT-III is required for phagophore closure and autophagosome- lysosome
        fusion.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: Functional multivesicular bodies are required for autophagic
            clearance of protein aggregates associated with neurodegenerative disease.
  - term:
      id: GO:1901673
      label: regulation of mitotic spindle assembly
    evidence_type: IMP
    original_reference_id: PMID:20616062
    review:
      summary: ESCRT-III depletion affects spindle assembly through effects on centrosomes.
      action: KEEP_AS_NON_CORE
      reason: Secondary effect of centrosome defects rather than direct regulatory
        function.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: Human ESCRT-III and VPS4 proteins are required for centrosome
            and spindle maintenance.
  - term:
      id: GO:1902774
      label: late endosome to lysosome transport
    evidence_type: IMP
    original_reference_id: PMID:17984323
    review:
      summary: CHMP2B is required for late endosome to lysosome transport based on
        cargo accumulation phenotype.
      action: ACCEPT
      reason: Core function of ESCRT pathway in endolysosomal trafficking.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: Functional multivesicular bodies are required for autophagic
            clearance of protein aggregates associated with neurodegenerative disease.
  - term:
      id: GO:1904930
      label: amphisome membrane
    evidence_type: IDA
    original_reference_id: PMID:17984323
    review:
      summary: CHMP2B localizes to amphisome membranes.
      action: ACCEPT
      reason: Amphisomes accumulate in ESCRT-depleted cells, indicating ESCRT function
        at this compartment.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: Functional multivesicular bodies are required for autophagic
            clearance of protein aggregates associated with neurodegenerative disease.
  - term:
      id: GO:0045296
      label: cadherin binding
    evidence_type: HDA
    original_reference_id: PMID:25468996
    review:
      summary: CHMP2B identified in E-cadherin interactome by quantitative proteomics.
      action: MARK_AS_OVER_ANNOTATED
      reason: High-throughput data without clear functional significance for CHMP2B
        core function. May represent transient interaction during membrane trafficking.
      supported_by:
        - reference_id: PMID:25468996
          supporting_text: E-cadherin interactome complexity and robustness resolved
            by quantitative proteomics.
  - term:
      id: GO:0016236
      label: macroautophagy
    evidence_type: TAS
    original_reference_id: PMID:20588296
    review:
      summary: CHMP2B participates in macroautophagy as part of ESCRT-III function.
      action: ACCEPT
      reason: ESCRT-III is required for autophagosome closure and maturation.
      supported_by:
        - reference_id: PMID:20588296
          supporting_text: "Jun 30. Membrane budding and scission by the ESCRT machinery:\
            \ it's all in the neck."
  - term:
      id: GO:0061763
      label: multivesicular body-lysosome fusion
    evidence_type: TAS
    original_reference_id: PMID:21118109
    review:
      summary: CHMP2B participates in MVB-lysosome fusion.
      action: ACCEPT
      reason: Core function of ESCRT pathway in endolysosomal trafficking.
      supported_by:
        - reference_id: PMID:21118109
          supporting_text: The role of ESCRT proteins in fusion events involving lysosomes,
            endosomes and autophagosomes.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:25468996
    review:
      summary: CHMP2B is detected in the cytoplasm.
      action: ACCEPT
      reason: CHMP2B exists in both cytosolic (soluble, inactive) and membrane- associated
        (active) forms.
      supported_by:
        - reference_id: PMID:25468996
          supporting_text: E-cadherin interactome complexity and robustness resolved
            by quantitative proteomics.
  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: TAS
    original_reference_id: PMID:24095276
    review:
      summary: CHMP2B is required for autophagy; genetic modifier studies with Syntaxin
        13.
      action: ACCEPT
      reason: Well-established function of ESCRT-III in autophagy.
      supported_by:
        - reference_id: PMID:24095276
          supporting_text: 2013 Oct 3. Syntaxin 13, a genetic modifier of mutant CHMP2B
            in frontotemporal dementia, is required for autophagosome maturation.
  - term:
      id: GO:0000815
      label: ESCRT III complex
    evidence_type: TAS
    original_reference_id: PMID:20588296
    review:
      summary: CHMP2B is a component of ESCRT-III complex.
      action: ACCEPT
      reason: Core component of ESCRT-III complex.
      supported_by:
        - reference_id: PMID:20588296
          supporting_text: "Jun 30. Membrane budding and scission by the ESCRT machinery:\
            \ it's all in the neck."
  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: TAS
    original_reference_id: PMID:17683935
    review:
      summary: CHMP2B is implicated in autophagy.
      action: ACCEPT
      reason: Validates ESCRT-III function in autophagy.
      supported_by:
        - reference_id: PMID:17683935
          supporting_text: 2007 Aug 2. ESCRT-III dysfunction causes autophagosome
            accumulation and neurodegeneration.
  - term:
      id: GO:0036258
      label: multivesicular body assembly
    evidence_type: TAS
    original_reference_id: PMID:20588296
    review:
      summary: CHMP2B participates in MVB assembly as part of ESCRT-III.
      action: ACCEPT
      reason: Core function of ESCRT-III in MVB biogenesis.
      supported_by:
        - reference_id: PMID:20588296
          supporting_text: "Jun 30. Membrane budding and scission by the ESCRT machinery:\
            \ it's all in the neck."
  - term:
      id: GO:0039702
      label: viral budding via host ESCRT complex
    evidence_type: TAS
    original_reference_id: PMID:20588296
    review:
      summary: CHMP2B participates in viral budding via ESCRT.
      action: ACCEPT
      reason: Well-established function of ESCRT-III.
      supported_by:
        - reference_id: PMID:20588296
          supporting_text: "Jun 30. Membrane budding and scission by the ESCRT machinery:\
            \ it's all in the neck."
  - term:
      id: GO:1904903
      label: ESCRT III complex disassembly
    evidence_type: NAS
    original_reference_id: PMID:20588296
    review:
      summary: CHMP2B is recycled during ESCRT-III complex disassembly by VPS4.
      action: ACCEPT
      reason: CHMP2B recruits VPS4 through its MIT-interacting motif for complex disassembly
        and recycling.
      supported_by:
        - reference_id: PMID:20588296
          supporting_text: "Jun 30. Membrane budding and scission by the ESCRT machinery:\
            \ it's all in the neck."
  - term:
      id: GO:0000815
      label: ESCRT III complex
    evidence_type: TAS
    original_reference_id: PMID:21118109
    review:
      summary: CHMP2B is a component of ESCRT-III complex.
      action: ACCEPT
      reason: Core component of ESCRT-III.
      supported_by:
        - reference_id: PMID:21118109
          supporting_text: The role of ESCRT proteins in fusion events involving lysosomes,
            endosomes and autophagosomes.
  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: TAS
    original_reference_id: PMID:21118109
    review:
      summary: CHMP2B is required for autophagy.
      action: ACCEPT
      reason: Well-established function.
      supported_by:
        - reference_id: PMID:21118109
          supporting_text: The role of ESCRT proteins in fusion events involving lysosomes,
            endosomes and autophagosomes.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17683935
    review:
      summary: CHMP2B interacts with CHMP2B from mouse (Q9D8B3).
      action: MARK_AS_OVER_ANNOTATED
      reason: Protein binding is not informative. This likely reflects homodimerization
        or ESCRT-III assembly.
      supported_by:
        - reference_id: PMID:17683935
          supporting_text: 2007 Aug 2. ESCRT-III dysfunction causes autophagosome
            accumulation and neurodegeneration.
  - term:
      id: GO:0000815
      label: ESCRT III complex
    evidence_type: IDA
    original_reference_id: PMID:24878737
    review:
      summary: CHMP2B is visualized as part of ESCRT-III spirals by cryo-EM.
      action: ACCEPT
      reason: Direct structural evidence for ESCRT-III complex membership.
      supported_by:
        - reference_id: PMID:24878737
          supporting_text: Structure of cellular ESCRT-III spirals and their relationship
            to HIV budding.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:24878737
    review:
      summary: CHMP2B detected in cytoplasm by imaging.
      action: ACCEPT
      reason: CHMP2B exists in cytoplasmic pool before membrane recruitment.
      supported_by:
        - reference_id: PMID:24878737
          supporting_text: Structure of cellular ESCRT-III spirals and their relationship
            to HIV budding.
  - term:
      id: GO:0005768
      label: endosome
    evidence_type: IDA
    original_reference_id: PMID:24878737
    review:
      summary: CHMP2B colocalizes with endosomes.
      action: ACCEPT
      reason: Core localization for ESCRT-III function.
      supported_by:
        - reference_id: PMID:24878737
          supporting_text: Structure of cellular ESCRT-III spirals and their relationship
            to HIV budding.
  - term:
      id: GO:0019076
      label: viral release from host cell
    evidence_type: IMP
    original_reference_id: PMID:23051622
    review:
      summary: CHMP2B is required for HIV-1 release based on depletion phenotype.
      action: ACCEPT
      reason: Well-established function of ESCRT-III in viral budding.
      supported_by:
        - reference_id: PMID:23051622
          supporting_text: ESCRT-III CHMP2A and CHMP3 form variable helical polymers
            in vitro and act synergistically during HIV-1 budding.
  - term:
      id: GO:0019076
      label: viral release from host cell
    evidence_type: IGI
    original_reference_id: PMID:23051622
    review:
      summary: CHMP2B functions with CHMP2A and CHMP3 in viral release.
      action: ACCEPT
      reason: Genetic interaction data supporting ESCRT-III function in viral budding.
      supported_by:
        - reference_id: PMID:23051622
          supporting_text: ESCRT-III CHMP2A and CHMP3 form variable helical polymers
            in vitro and act synergistically during HIV-1 budding.
  - term:
      id: GO:0039702
      label: viral budding via host ESCRT complex
    evidence_type: IMP
    original_reference_id: PMID:23051622
    review:
      summary: CHMP2B is required for viral budding.
      action: ACCEPT
      reason: Direct functional evidence.
      supported_by:
        - reference_id: PMID:23051622
          supporting_text: ESCRT-III CHMP2A and CHMP3 form variable helical polymers
            in vitro and act synergistically during HIV-1 budding.
  - term:
      id: GO:0070050
      label: neuron cellular homeostasis
    evidence_type: IMP
    original_reference_id: PMID:16807408
    review:
      summary: CHMP2B mutations disrupt neuronal homeostasis, causing ALS/FTD phenotypes.
      action: ACCEPT
      reason: Clinically validated function. CHMP2B mutations cause neurodegenerative
        disease through disruption of neuronal homeostasis.
      supported_by:
        - reference_id: PMID:16807408
          supporting_text: Epub 2006 Jun 28. ALS phenotypes with mutations in CHMP2B
            (charged multivesicular body protein 2B).
  - term:
      id: GO:0005764
      label: lysosome
    evidence_type: IDA
    original_reference_id: PMID:16041373
    review:
      summary: CHMP2B colocalizes with lysosomes.
      action: ACCEPT
      reason: Supports ESCRT function in endolysosomal pathway.
      supported_by:
        - reference_id: PMID:16041373
          supporting_text: Mutations in the endosomal ESCRTIII-complex subunit CHMP2B
            in frontotemporal dementia.
  - term:
      id: GO:0005770
      label: late endosome
    evidence_type: IDA
    original_reference_id: PMID:16041373
    review:
      summary: CHMP2B colocalizes with late endosomes.
      action: ACCEPT
      reason: Core localization for ESCRT-III function.
      supported_by:
        - reference_id: PMID:16041373
          supporting_text: Mutations in the endosomal ESCRTIII-complex subunit CHMP2B
            in frontotemporal dementia.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IDA
    original_reference_id: PMID:16041373
    review:
      summary: CHMP2B is present in cytosol.
      action: ACCEPT
      reason: Soluble form of CHMP2B before membrane recruitment.
      supported_by:
        - reference_id: PMID:16041373
          supporting_text: Mutations in the endosomal ESCRTIII-complex subunit CHMP2B
            in frontotemporal dementia.
  - term:
      id: GO:0007032
      label: endosome organization
    evidence_type: IMP
    original_reference_id: PMID:16041373
    review:
      summary: CHMP2B is required for endosome organization; mutations cause enlarged
        endosomes.
      action: ACCEPT
      reason: Core function of ESCRT-III in endosomal compartment organization.
      supported_by:
        - reference_id: PMID:16041373
          supporting_text: Mutations in the endosomal ESCRTIII-complex subunit CHMP2B
            in frontotemporal dementia.
  - term:
      id: GO:0050890
      label: cognition
    evidence_type: IMP
    original_reference_id: PMID:16041373
    review:
      summary: CHMP2B mutations affect cognition, causing frontotemporal dementia.
      action: KEEP_AS_NON_CORE
      reason: This is a disease phenotype resulting from disrupted ESCRT function
        rather than a direct molecular function of CHMP2B. The cognitive deficits
        arise from neuronal dysfunction secondary to endolysosomal/ autophagy defects.
      supported_by:
        - reference_id: PMID:16041373
          supporting_text: Mutations in the endosomal ESCRTIII-complex subunit CHMP2B
            in frontotemporal dementia.
  - term:
      id: GO:0070050
      label: neuron cellular homeostasis
    evidence_type: IMP
    original_reference_id: PMID:16041373
    review:
      summary: CHMP2B is required for neuronal homeostasis.
      action: ACCEPT
      reason: Validated by disease phenotypes. ESCRT-III function is essential for
        neuronal health through its roles in autophagy and endolysosomal trafficking.
      supported_by:
        - reference_id: PMID:16041373
          supporting_text: Mutations in the endosomal ESCRTIII-complex subunit CHMP2B
            in frontotemporal dementia.
  - term:
      id: GO:0010824
      label: regulation of centrosome duplication
    evidence_type: IMP
    original_reference_id: PMID:20616062
    review:
      summary: ESCRT-III depletion affects centrosome numbers.
      action: KEEP_AS_NON_CORE
      reason: This appears to be a secondary effect of ESCRT-III depletion rather
        than a direct regulatory function. The mechanism is unclear.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: Human ESCRT-III and VPS4 proteins are required for centrosome
            and spindle maintenance.
  - term:
      id: GO:0039702
      label: viral budding via host ESCRT complex
    evidence_type: IGI
    original_reference_id: PMID:24107264
    review:
      summary: CHMP2B functions in EIAV budding via ESCRT.
      action: ACCEPT
      reason: Extends viral budding function to other lentiviruses beyond HIV-1.
      supported_by:
        - reference_id: PMID:24107264
          supporting_text: ESCRT requirements for EIAV budding.
  - term:
      id: GO:0070062
      label: extracellular exosome
    evidence_type: HDA
    original_reference_id: PMID:23533145
    review:
      summary: CHMP2B detected in exosome proteomics.
      action: KEEP_AS_NON_CORE
      reason: ESCRT-III may be captured in exosomes during MVB-plasma membrane fusion
        but is not a core exosome component. This may reflect co-fractionation during
        exosome biogenesis.
      supported_by:
        - reference_id: PMID:23533145
          supporting_text: 2013 Apr 23. In-depth proteomic analyses of exosomes isolated
            from expressed prostatic secretions in urine.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21975012
    review:
      summary: CHMP2B interacts with CHMP4B.
      action: MARK_AS_OVER_ANNOTATED
      reason: Protein binding is not informative. This reflects ESCRT-III complex
        assembly.
      supported_by:
        - reference_id: PMID:21975012
          supporting_text: ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate
            transmembrane cargos in hESC-derived human neurons.
  - term:
      id: GO:0070062
      label: extracellular exosome
    evidence_type: HDA
    original_reference_id: PMID:19056867
    review:
      summary: CHMP2B detected in urinary exosome proteomics.
      action: KEEP_AS_NON_CORE
      reason: Same as above - likely co-fractionation during exosome biogenesis.
      supported_by:
        - reference_id: PMID:19056867
          supporting_text: 2008 Dec 3. Large-scale proteomics and phosphoproteomics
            of urinary exosomes.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-3159232
    review:
      summary: Reactome annotation for HIV virion budding machinery.
      action: ACCEPT
      reason: CHMP2B is present in cytosol as part of viral budding pathway.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-917693
    review:
      summary: Reactome annotation for ESCRT disassembly.
      action: ACCEPT
      reason: CHMP2B is in cytosol after VPS4-mediated disassembly.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-917700
    review:
      summary: Reactome annotation for MVB vesicle formation.
      action: ACCEPT
      reason: CHMP2B cycles between cytosol and membrane.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9668389
    review:
      summary: Reactome annotation for NE fenestration.
      action: ACCEPT
      reason: CHMP2B is in cytosol before recruitment to NE.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9668395
    review:
      summary: Reactome annotation for CHMP7-CC2D1B binding.
      action: ACCEPT
      reason: CHMP2B is in cytosol during this pathway.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9668398
    review:
      summary: Reactome annotation for CHMP7-CHMP4B binding and ESCRT-III recruitment.
      action: ACCEPT
      reason: CHMP2B is in cytosol before membrane recruitment.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9668405
    review:
      summary: Reactome annotation for spastin binding to IST1.
      action: ACCEPT
      reason: CHMP2B is in cytosol during this pathway.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9668415
    review:
      summary: Reactome annotation for VPS4-mediated ESCRT-III disassembly.
      action: ACCEPT
      reason: CHMP2B returns to cytosol after disassembly.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9668419
    review:
      summary: Reactome annotation for spastin-mediated microtubule severing.
      action: ACCEPT
      reason: CHMP2B is in cytosol during this pathway.
  - term:
      id: GO:0019904
      label: protein domain specific binding
    evidence_type: IPI
    original_reference_id: PMID:17928862
    review:
      summary: CHMP2B binds VPS4A and VPS4B through its MIT-interacting motif.
      action: ACCEPT
      reason: Well-characterized domain-specific interaction essential for ESCRT-III
        recycling. Structural data confirms the MIT-MIM interaction.
      supported_by:
        - reference_id: PMID:17928862
          supporting_text: ESCRT-III recognition by VPS4 ATPases.
  - term:
      id: GO:0180024
      label: membrane grommet activity
    evidence_type: NAS
    review:
      summary: Added to align core_functions with existing annotations.
      action: NEW
      reason: Core function term not present in existing_annotations.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: autophagic degradation is inhibited in cells depleted of
            ESCRT subunits and in cells expressing CHMP2B mutants
core_functions:
  - molecular_function:
      id: GO:0180024
      label: membrane grommet activity
    directly_involved_in:
      - id: GO:0071985
        label: multivesicular body sorting pathway
    locations:
      - id: GO:0005771
        label: multivesicular body
      - id: GO:0032585
        label: multivesicular body membrane
    in_complex:
      id: GO:0000815
      label: ESCRT III complex
    description: CHMP2B is a core subunit of the ESCRT-III complex that mediates membrane
      fission during intraluminal vesicle formation in MVBs.
    supported_by:
      - reference_id: PMID:19234443
        supporting_text: Three subunits of ESCRT-III, Vps20, Snf7, and Vps24, were
          sufficient to detach intralumenal vesicles
  - molecular_function:
      id: GO:0180024
      label: membrane grommet activity
    directly_involved_in:
      - id: GO:0061952
        label: midbody abscission
    locations:
      - id: GO:0030496
        label: midbody
    in_complex:
      id: GO:0000815
      label: ESCRT III complex
    description: CHMP2B performs membrane fission at the midbody during cytokinetic
      abscission.
    supported_by:
      - reference_id: PMID:20616062
        supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human
          ESCRT-III (CHMP) proteins inhibited abscission
  - molecular_function:
      id: GO:0180024
      label: membrane grommet activity
    directly_involved_in:
      - id: GO:0031468
        label: nuclear membrane reassembly
    in_complex:
      id: GO:0000815
      label: ESCRT III complex
    description: CHMP2B mediates membrane sealing during nuclear envelope reformation
      at telophase.
    supported_by:
      - reference_id: PMID:26040713
        supporting_text: the endosomal sorting complex required for transport-III
          (ESCRT-III) machinery localizes to sites of annular fusion in the forming
          NE in human cells
  - molecular_function:
      id: GO:0180024
      label: membrane grommet activity
    directly_involved_in:
      - id: GO:0039702
        label: viral budding via host ESCRT complex
    locations:
      - id: GO:0005886
        label: plasma membrane
    in_complex:
      id: GO:0000815
      label: ESCRT III complex
    description: CHMP2B mediates membrane fission during viral budding at the plasma
      membrane.
    supported_by:
      - reference_id: PMID:24878737
        supporting_text: Structure of cellular ESCRT-III spirals and their relationship
          to HIV budding
  - molecular_function:
      id: GO:0180024
      label: membrane grommet activity
    directly_involved_in:
      - id: GO:0097352
        label: autophagosome maturation
    locations:
      - id: GO:0000421
        label: autophagosome membrane
    in_complex:
      id: GO:0000815
      label: ESCRT III complex
    description: CHMP2B mediates membrane sealing during phagophore closure.
    supported_by:
      - reference_id: PMID:17984323
        supporting_text: autophagic degradation is inhibited in cells depleted of
          ESCRT subunits and in cells expressing CHMP2B mutants
  - molecular_function:
      id: GO:0019904
      label: protein domain specific binding
    directly_involved_in:
      - id: GO:1904903
        label: ESCRT III complex disassembly
    locations:
      - id: GO:0005829
        label: cytosol
    in_complex:
      id: GO:0000815
      label: ESCRT III complex
    description: CHMP2B binds VPS4 ATPases through its MIT-interacting motif (MIM),
      enabling ESCRT-III complex disassembly.
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with GO
      terms
    findings:
      - statement: CHMP2B contains the Snf7 domain which maps to vacuolar transport
          function
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings:
      - statement: CHMP2B function as an ESCRT-III subunit is conserved across eukaryotes
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
    findings:
      - statement: Protein transport keyword maps to GO:0015031
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
      vocabulary mapping
    findings:
      - statement: CHMP2B subcellular location annotations derived from UniProt
  - id: GO_REF:0000117
    title: Electronic Gene Ontology annotations created by ARBA machine learning models
    findings:
      - statement: ARBA predictions for CHMP2B localization and function generally
          accurate
  - id: PMID:16041373
    title: Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal
      dementia
    findings:
      - statement: First identification of CHMP2B mutations in FTD
      - statement: CHMP2B localizes to late endosomes, lysosomes, and cytosol
      - statement: Mutations cause enlarged endosomes and neuronal dysfunction
  - id: PMID:16505166
    title: Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved
      VSL region in Vta1
    findings:
      - statement: ESCRT-III subunits are recycled by VPS4 for multiple rounds of
          MVB formation
  - id: PMID:16554368
    title: The ESCRT-III subunit hVps24 is required for degradation but not silencing
      of the epidermal growth factor receptor
    findings:
      - statement: ESCRT-III localizes to MVB membranes
      - statement: Required for MVB sorting pathway function
  - id: PMID:16730941
    title: "A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex."
    findings:
      - statement: CHMP2B interacts with CHMP3 and other ESCRT-III subunits
      - statement: MIT domain-containing proteins bind to multiple ESCRT-III components
  - id: PMID:16807408
    title: "ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B)."
    findings:
      - statement: CHMP2B mutations cause ALS phenotypes
      - statement: Expands disease spectrum beyond FTD
  - id: PMID:17683935
    title: ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration.
    findings:
      - statement: CHMP2B is required for autophagy
  - id: PMID:17928862
    title: ESCRT-III recognition by VPS4 ATPases
    findings:
      - statement: Structure of CHMP2B MIT-interacting motif with VPS4B
      - statement: CHMP2B binds VPS4A and VPS4B for complex disassembly
  - id: PMID:17984323
    title: Functional multivesicular bodies are required for autophagic clearance
      of protein aggregates associated with neurodegenerative disease
    findings:
      - statement: ESCRT depletion or CHMP2B mutants inhibit autophagy
      - statement: Causes accumulation of ubiquitin/p62-positive aggregates
      - statement: CHMP2B mutations disrupt TDP-43 clearance
      - statement: Links ESCRT dysfunction to neurodegeneration
  - id: PMID:19056867
    title: Large-scale proteomics and phosphoproteomics of urinary exosomes
    findings:
      - statement: CHMP2B detected in urinary exosome proteome
  - id: PMID:19234443
    title: Membrane scission by the ESCRT-III complex
    findings:
      - statement: ESCRT-III alone can drive membrane fission
      - statement: Three ESCRT-III subunits sufficient for vesicle detachment
      - statement: VPS4 required for recycling, not scission
  - id: PMID:20588296
    title: "Membrane budding and scission by the ESCRT machinery: it's all in the\
      \ neck."
    findings:
      - statement: Review of ESCRT-III mechanism in membrane remodeling
  - id: PMID:20616062
    title: Human ESCRT-III and VPS4 proteins are required for centrosome and spindle
      maintenance
    findings:
      - statement: ESCRT-III depletion inhibits abscission
      - statement: Also affects centrosome and spindle maintenance
      - statement: VPS4 localizes to spindle poles and midbodies
  - id: PMID:21118109
    title: The role of ESCRT proteins in fusion events involving lysosomes, endosomes
      and autophagosomes.
    findings:
      - statement: CHMP2B participates in autophagy and MVB-lysosome fusion
  - id: PMID:21975012
    title: ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate transmembrane
      cargos in hESC-derived human neurons.
    findings:
      - statement: CHMP2B interacts with CHMP4B for ESCRT-III assembly
  - id: PMID:22046132
    title: 'The SARS-coronavirus-host interactome: identification of cyclophilins
      as target for pan-coronavirus inhibitors.'
    findings:
      - statement: CHMP2B interacts with viral Rep proteins
  - id: PMID:23051622
    title: ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and
      act synergistically during HIV-1 budding
    findings:
      - statement: ESCRT-III forms helical polymers
      - statement: CHMP2A and CHMP3 act synergistically in viral budding
  - id: PMID:23533145
    title: In-depth proteomic analyses of exosomes isolated from expressed prostatic
      secretions in urine
    findings:
      - statement: CHMP2B detected in exosome proteome
  - id: PMID:24095276
    title: Syntaxin 13, a genetic modifier of mutant CHMP2B in frontotemporal dementia,
      is required for autophagosome maturation
    findings:
      - statement: Syntaxin 13 is a genetic modifier of CHMP2B
      - statement: Both are required for autophagosome maturation
  - id: PMID:24107264
    title: ESCRT requirements for EIAV budding
    findings:
      - statement: ESCRT-III required for equine lentivirus budding
  - id: PMID:24482116
    title: ESCRT machinery is required for plasma membrane repair
    findings:
      - statement: ESCRT performs membrane sealing during plasma membrane repair
  - id: PMID:24878737
    title: Structure of cellular ESCRT-III spirals and their relationship to HIV budding
    findings:
      - statement: Cryo-EM structure of ESCRT-III spirals
      - statement: Direct visualization at HIV budding sites
  - id: PMID:25468996
    title: E-cadherin interactome complexity and robustness resolved by quantitative
      proteomics
    findings:
      - statement: CHMP2B detected in E-cadherin interactome
  - id: PMID:26040712
    title: Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear
      envelope sealing
    findings:
      - statement: ESCRT-III recruited to NE during anaphase
      - statement: Coordinates with spastin for spindle disassembly
      - statement: Localizes to kinetochores and midbody
  - id: PMID:26040713
    title: ESCRT-III controls nuclear envelope reformation
    findings:
      - statement: CHMP2A/B encircle forming daughter nuclei during telophase
      - statement: ESCRT-III localizes to sites of annular fusion
      - statement: Required for NE integrity and sealing
  - id: PMID:26496610
    title: A human interactome in three quantitative dimensions organized by stoichiometries
      and abundances
    findings:
      - statement: CHMP2B-CHMP4B interaction confirmed
  - id: Reactome:R-HSA-3159232
    title: Recruitment Of HIV Virion Budding Machinery
    findings:
      - statement: CHMP2B participates in HIV budding pathway
  - id: Reactome:R-HSA-917693
    title: ESCRT Disassembly
    findings:
      - statement: CHMP2B is recycled by VPS4
  - id: Reactome:R-HSA-917700
    title: MVB Vesicle Formation
    findings:
      - statement: CHMP2B functions in MVB formation
  - id: Reactome:R-HSA-9668389
    title: VPS4 binds ESCRT-III assemblies at nuclear envelope (NE) fenestrations
    findings:
      - statement: CHMP2B participates in NE sealing pathway
  - id: Reactome:R-HSA-9668395
    title: CHMP7 binds CC2D1B
    findings:
      - statement: CHMP2B in ESCRT-III NE recruitment pathway
  - id: Reactome:R-HSA-9668398
    title: CHMP7 binds CHMP4B, which recruits other subunits of the ESCRT-III complex
    findings:
      - statement: CHMP2B recruited as part of ESCRT-III assembly at NE
  - id: Reactome:R-HSA-9668405
    title: SPAST (spastin) binds the IST1 subunit of ESCRT-III at the sites of microtubule
      attachment to chromatin
    findings:
      - statement: CHMP2B in pathway with spastin and IST1
  - id: Reactome:R-HSA-9668415
    title: VPS4 mediates disassembly of ESCRTIII subunits to promote sealing of holes
      in the nuclear envelope
    findings:
      - statement: CHMP2B disassembled by VPS4 during NE sealing
  - id: Reactome:R-HSA-9668419
    title: SPAST (spastin) mediates the severing of microtubules at chromosome attachment
      sites
    findings:
      - statement: CHMP2B in pathway coordinating spindle disassembly and NE sealing
  - id: PMID:21044950
    title: Genome-wide YFP fluorescence complementation screen identifies new regulators
      for telomere signaling in human cells.
    findings:
      - statement: CHMP2B interacts with TERF2IP in yeast two-hybrid screen
  - id: file:human/CHMP2B/CHMP2B-deep-research-falcon.md
    title: Deep research report on CHMP2B
    findings: []
proposed_new_terms: []
suggested_questions:
  - question: What is the precise stoichiometry of CHMP2B within ESCRT-III polymers?
  - question: How does K6 methylation by SMYD2 regulate CHMP2B polymerization dynamics?
  - question: Are there tissue-specific differences in CHMP2B function that explain
      selective neuronal vulnerability in FTD/ALS?
suggested_experiments:
  - description: Structural studies of CHMP2B in the context of full ESCRT-III polymers
      at near-atomic resolution
  - description: Live-cell imaging of CHMP2B dynamics during nuclear envelope reformation
  - description: Proteomics of CHMP2B interactome in neurons versus non-neuronal cells

Gene Description

Existing Annotations Review

Core Functions

CHMP2B is a core subunit of the ESCRT-III complex that mediates membrane fission during intraluminal vesicle formation in MVBs.

CHMP2B performs membrane fission at the midbody during cytokinetic abscission.

CHMP2B mediates membrane sealing during nuclear envelope reformation at telophase.

CHMP2B mediates membrane fission during viral budding at the plasma membrane.

CHMP2B mediates membrane sealing during phagophore closure.

CHMP2B binds VPS4 ATPases through its MIT-interacting motif (MIM), enabling ESCRT-III complex disassembly.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Citations

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