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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005771 multivesicular body | IBA GO_REF:0000033 | ACCEPT | 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). 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. Supporting Evidence: file:human/CHMP2B/CHMP2B-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0015031 protein transport | IBA GO_REF:0000033 | ACCEPT | Summary: CHMP2B participates in protein transport through its role in the MVB pathway, which sorts ubiquitinated membrane proteins for lysosomal degradation. 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. |
| GO:0032509 endosome transport via multivesicular body sorting pathway | IBA GO_REF:0000033 | ACCEPT | Summary: CHMP2B is essential for the MVB sorting pathway, mediating endosomal cargo transport through its role in intraluminal vesicle formation. 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. |
| GO:0045324 late endosome to vacuole transport | IBA GO_REF:0000033 | ACCEPT | Summary: CHMP2B participates in transport from late endosomes to lysosomes (the mammalian equivalent of vacuoles) through its role in MVB biogenesis and fusion. 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. |
| GO:0000815 ESCRT III complex | IBA GO_REF:0000033 | ACCEPT | Summary: CHMP2B is a bona fide subunit of the ESCRT-III complex, confirmed by both phylogenetic analysis and direct biochemical evidence. 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. |
| GO:0000776 kinetochore | IEA GO_REF:0000117 | ACCEPT | Summary: ESCRT-III components including CHMP2B have been shown to localize to kinetochores during mitosis, supported by IDA evidence from PMID:26040712. 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. |
| GO:0001778 plasma membrane repair | IEA GO_REF:0000117 | ACCEPT | Summary: ESCRT-III machinery is required for plasma membrane repair, supported by IDA evidence from PMID:24482116. 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. |
| GO:0005643 nuclear pore | IEA GO_REF:0000117 | KEEP AS NON CORE | 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. 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. |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP2B localizes to lysosomal membranes as part of the endolysosomal pathway, supported by IDA evidence from PMID:17984323. Reason: The annotation is supported by direct experimental evidence showing CHMP2B localization to lysosomal membranes in the context of autophagy and MVB-lysosome fusion. |
| GO:0005828 kinetochore microtubule | IEA GO_REF:0000117 | ACCEPT | Summary: ESCRT-III components localize to kinetochore microtubules during mitosis, supported by IDA evidence from PMID:26040712. Reason: This annotation is validated by direct experimental evidence showing ESCRT-III localization at spindle poles and kinetochore microtubules. |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: CHMP2B is present in the cytosol in its soluble, inactive form before recruitment to membranes. 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. |
| GO:0007034 vacuolar transport | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based annotation reflecting CHMP2B's role in vacuolar/lysosomal transport as an ESCRT-III subunit. Reason: The SNF7 domain annotation appropriately maps to vacuolar transport function. In mammalian cells, this corresponds to lysosomal transport pathways. |
| GO:0007080 mitotic metaphase chromosome alignment | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ESCRT-III depletion affects chromosome alignment during mitosis, supported by IMP evidence from PMID:20616062. 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. |
| GO:0015031 protein transport | IEA GO_REF:0000043 | ACCEPT | Summary: UniProt keyword-based annotation for protein transport, reflecting CHMP2B's role in sorting and trafficking. 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. |
| GO:0030496 midbody | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP2B localizes to the midbody during cytokinesis, supported by IDA evidence from PMID:26040712. Reason: Midbody localization is a core feature of ESCRT-III function in cytokinetic abscission. Well-validated by direct experimental evidence. |
| GO:0031468 nuclear membrane reassembly | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP2B participates in nuclear envelope reformation during telophase, supported by IMP evidence from PMID:26040713. Reason: This is a validated core function of ESCRT-III. The complex is recruited to sites of annular fusion during nuclear envelope reformation. |
| GO:0031902 late endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: CHMP2B localizes to late endosome membranes as part of the MVB pathway. Reason: Core localization for ESCRT-III function in MVB biogenesis. Late endosomes are the site of intraluminal vesicle formation. |
| GO:0032585 multivesicular body membrane | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP2B localizes to MVB membranes, supported by IDA evidence from PMID:16554368. Reason: Core localization for ESCRT-III function. This is the primary site where CHMP2B functions in intraluminal vesicle formation. |
| GO:0039702 viral budding via host ESCRT complex | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP2B participates in viral budding processes, particularly for HIV-1, supported by IDA evidence from PMID:24878737 and IMP from PMID:23051622. 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. |
| GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP2B is essential for MVB-mediated degradation of ubiquitinated cargo proteins, supported by IDA evidence from PMID:17984323. Reason: Core function of the ESCRT pathway. CHMP2B is required for proper sorting and degradation of ubiquitinated membrane proteins through the MVB pathway. |
| GO:0046761 viral budding from plasma membrane | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP2B participates in viral budding from the plasma membrane, supported by IDA evidence from PMID:24878737. Reason: HIV-1 and other enveloped viruses bud from the plasma membrane using ESCRT machinery. This is a validated function for ESCRT-III components. |
| GO:0061952 midbody abscission | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP2B is required for the final abscission step of cytokinesis, supported by IMP evidence from PMID:20616062. Reason: Core function of ESCRT-III. The complex mediates membrane fission at the midbody to complete cell division. |
| GO:0071985 multivesicular body sorting pathway | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP2B is essential for the MVB sorting pathway, supported by IDA evidence from PMID:16554368. Reason: This is the primary biological process in which CHMP2B functions as an ESCRT-III subunit. |
| GO:0097352 autophagosome maturation | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP2B is required for autophagosome maturation, supported by IMP evidence from PMID:17984323. Reason: The ESCRT machinery is required for phagophore closure and autophagosome- lysosome fusion. CHMP2B mutations cause defects in autophagy. |
| GO:1901673 regulation of mitotic spindle assembly | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ESCRT-III depletion affects spindle assembly, supported by IMP evidence from PMID:20616062. 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. |
| GO:1902774 late endosome to lysosome transport | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP2B is required for late endosome to lysosome transport, supported by IMP evidence from PMID:17984323. Reason: Core function of ESCRT-III in the endolysosomal pathway. MVB-lysosome fusion requires functional ESCRT machinery. |
| GO:1904930 amphisome membrane | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP2B localizes to amphisome membranes, supported by IDA evidence from PMID:17984323. Reason: Amphisomes are intermediates between autophagosomes and lysosomes. ESCRT depletion causes accumulation of amphisomes, indicating CHMP2B function at this compartment. |
| GO:0005515 protein binding | IPI PMID:16730941 A systematic analysis of human CHMP protein interactions: ad... | MARK AS OVER ANNOTATED | Summary: CHMP2B interacts with CHMP3 (PMID:16730941). While protein binding is too general, this reflects specific ESCRT-III complex assembly. Reason: Protein binding is not informative. The specific interaction with CHMP3 would be better captured as ESCRT-III complex assembly function. Proposed replacements: ESCRT III complex Supporting Evidence: PMID:16730941 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. |
| GO:0005515 protein binding | IPI PMID:21044950 Genome-wide YFP fluorescence complementation screen identifi... | MARK AS OVER ANNOTATED | Summary: CHMP2B interacts with TERF2IP in a YFP fluorescence complementation screen for telomere signaling regulators. Reason: Protein binding is not informative. This appears to be a high-throughput screen result without clear functional significance for CHMP2B. Supporting Evidence: PMID:21044950 Epub 2010 Nov 2. Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells. |
| GO:0005515 protein binding | IPI PMID:22046132 The SARS-coronavirus-host interactome: identification of cyc... | MARK AS OVER ANNOTATED | Summary: CHMP2B interacts with viral Rep proteins based on IntAct data. Reason: Protein binding is not informative. The viral interaction would be better described in the context of viral budding function. Supporting Evidence: PMID:22046132 2011 Oct 27. The SARS-coronavirus-host interactome: identification of cyclophilins as target for pan-coronavirus inhibitors. |
| GO:0005515 protein binding | IPI PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in... | MARK AS OVER ANNOTATED | Summary: CHMP2B interacts with CHMP4B and CHMP3 as part of ESCRT-III assembly during HIV-1 budding. Reason: Protein binding is not informative. These interactions reflect ESCRT-III complex assembly, better captured by complex membership annotation. Supporting Evidence: PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MARK AS OVER ANNOTATED | Summary: CHMP2B interacts with CHMP4B in stoichiometry studies. Reason: Protein binding is not informative. Better captured by ESCRT-III complex membership. Supporting Evidence: PMID:26496610 Oct 22. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. |
| GO:0000421 autophagosome membrane | IDA PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: CHMP2B localizes to autophagosome membranes based on direct observation in cells expressing CHMP2B mutants and controls. Reason: This localization is functionally relevant as ESCRT machinery is required for phagophore closure during autophagosome formation. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. |
| GO:0000776 kinetochore | IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly... | ACCEPT | Summary: ESCRT-III components localize to kinetochores during mitosis based on immunofluorescence. Reason: Validated localization that supports the mitotic functions of ESCRT-III. Supporting Evidence: PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing. |
| GO:0001778 plasma membrane repair | IDA PMID:24482116 ESCRT machinery is required for plasma membrane repair | ACCEPT | Summary: The ESCRT machinery is required for plasma membrane repair based on functional studies. Reason: ESCRT-III mediates membrane sealing during plasma membrane repair, analogous to its function in other membrane fission events. Supporting Evidence: PMID:24482116 2014 Jan 30. ESCRT machinery is required for plasma membrane repair. |
| GO:0005765 lysosomal membrane | IDA PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: CHMP2B localizes to lysosomal membranes in the context of autophagy and MVB-lysosome fusion. Reason: Functional localization supporting ESCRT role in endolysosomal trafficking. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. |
| GO:0005828 kinetochore microtubule | IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly... | ACCEPT | Summary: ESCRT-III components localize to kinetochore microtubules during mitosis. Reason: This localization supports ESCRT-III function in spindle maintenance. Supporting Evidence: PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing. |
| GO:0005886 plasma membrane | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: CHMP2B localizes to the plasma membrane during viral budding and membrane repair processes. Reason: Functional localization for ESCRT-III in plasma membrane fission events. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding. |
| GO:0006914 autophagy | IMP PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: CHMP2B is required for autophagy based on mutant phenotype analysis. CHMP2B mutants cause accumulation of autophagic compartments and protein aggregates. Reason: This is a core function demonstrated by disease-causing mutations. ESCRT-III is required for autophagosome closure and amphisome-lysosome fusion. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. |
| GO:0006997 nucleus organization | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | KEEP AS NON CORE | Summary: ESCRT-III depletion causes nuclear morphology defects. Reason: This is a secondary consequence of defects in nuclear envelope reformation and spindle function rather than a primary regulatory role in nucleus organization. Supporting Evidence: PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance. |
| GO:0007080 mitotic metaphase chromosome alignment | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | KEEP AS NON CORE | Summary: ESCRT-III depletion affects chromosome alignment during mitosis. Reason: This is a secondary consequence of centrosome/spindle defects rather than a direct function in chromosome alignment. Supporting Evidence: PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance. |
| GO:0030496 midbody | IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly... | ACCEPT | Summary: ESCRT-III components localize to the midbody during cytokinesis based on immunofluorescence. Reason: Core localization for ESCRT-III function in cytokinetic abscission. Supporting Evidence: PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing. |
| GO:0031468 nuclear membrane reassembly | IMP PMID:26040713 ESCRT-III controls nuclear envelope reformation | ACCEPT | Summary: CHMP2B is required for nuclear envelope reformation based on functional depletion studies. Reason: Core function of ESCRT-III in sealing the nuclear envelope during telophase. Well-validated by two independent studies. Supporting Evidence: PMID:26040713 ESCRT-III controls nuclear envelope reformation. |
| GO:0032585 multivesicular body membrane | IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but... | ACCEPT | Summary: CHMP2B localizes to MVB membranes based on immunofluorescence and functional studies. Reason: Core localization for ESCRT-III function in MVB biogenesis. Supporting Evidence: PMID:16554368 Mar 22. The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptor. |
| GO:0036258 multivesicular body assembly | NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a... | ACCEPT | Summary: CHMP2B participates in MVB assembly as an ESCRT-III subunit. Reason: Core function of ESCRT-III. Well-established through multiple lines of evidence. Supporting Evidence: PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1. |
| GO:0039702 viral budding via host ESCRT complex | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: CHMP2B is directly visualized forming spirals during HIV budding. Reason: Direct structural evidence for ESCRT-III function in viral budding. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding. |
| GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | IDA PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: CHMP2B is required for MVB-mediated degradation of ubiquitinated proteins based on direct demonstration of cargo accumulation. Reason: Core function of ESCRT pathway. CHMP2B is essential for sorting ubiquitinated cargo into MVBs for degradation. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. |
| GO:0046761 viral budding from plasma membrane | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: CHMP2B forms spirals at the plasma membrane during viral budding. Reason: Direct visualization of ESCRT-III at budding sites on plasma membrane. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding. |
| GO:0051469 vesicle fusion with vacuole | NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a... | MODIFY | Summary: CHMP2B participates in MVB-lysosome fusion (mammalian equivalent of vesicle-vacuole fusion). Reason: In mammalian cells, this process is MVB-lysosome fusion. The term is more appropriate for yeast. Proposed replacements: multivesicular body-lysosome fusion Supporting Evidence: PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1. |
| GO:0061763 multivesicular body-lysosome fusion | NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a... | ACCEPT | Summary: CHMP2B participates in MVB-lysosome fusion as an ESCRT-III subunit. Reason: ESCRT-III function is required for efficient MVB-lysosome fusion. Supporting Evidence: PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1. |
| GO:0061952 midbody abscission | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | ACCEPT | Summary: CHMP2B is required for cytokinetic abscission based on depletion phenotype. Reason: Core function of ESCRT-III. The complex mediates the final membrane fission step of cytokinesis. Supporting Evidence: PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance. |
| GO:0071985 multivesicular body sorting pathway | IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but... | ACCEPT | Summary: CHMP2B is essential for MVB sorting pathway function. Reason: Primary biological process for ESCRT-III function. Supporting Evidence: PMID:16554368 Mar 22. The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptor. |
| GO:0090148 membrane fission | NAS PMID:19234443 Membrane scission by the ESCRT-III complex | ACCEPT | Summary: ESCRT-III directly mediates membrane fission based on reconstitution studies. Reason: Core molecular function of ESCRT-III. The complex drives membrane scission in multiple contexts. Supporting Evidence: PMID:19234443 Membrane scission by the ESCRT-III complex. |
| GO:0097352 autophagosome maturation | IMP PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: CHMP2B is required for autophagosome maturation based on mutant phenotype. Reason: ESCRT-III is required for phagophore closure and autophagosome- lysosome fusion. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. |
| GO:1901673 regulation of mitotic spindle assembly | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | KEEP AS NON CORE | Summary: ESCRT-III depletion affects spindle assembly through effects on centrosomes. Reason: Secondary effect of centrosome defects rather than direct regulatory function. Supporting Evidence: PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance. |
| GO:1902774 late endosome to lysosome transport | IMP PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: CHMP2B is required for late endosome to lysosome transport based on cargo accumulation phenotype. Reason: Core function of ESCRT pathway in endolysosomal trafficking. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. |
| GO:1904930 amphisome membrane | IDA PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: CHMP2B localizes to amphisome membranes. Reason: Amphisomes accumulate in ESCRT-depleted cells, indicating ESCRT function at this compartment. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | MARK AS OVER ANNOTATED | Summary: CHMP2B identified in E-cadherin interactome by quantitative proteomics. Reason: High-throughput data without clear functional significance for CHMP2B core function. May represent transient interaction during membrane trafficking. Supporting Evidence: PMID:25468996 E-cadherin interactome complexity and robustness resolved by quantitative proteomics. |
| GO:0016236 macroautophagy | TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: CHMP2B participates in macroautophagy as part of ESCRT-III function. Reason: ESCRT-III is required for autophagosome closure and maturation. Supporting Evidence: PMID:20588296 Jun 30. Membrane budding and scission by the ESCRT machinery: it's all in the neck. |
| GO:0061763 multivesicular body-lysosome fusion | TAS PMID:21118109 The role of ESCRT proteins in fusion events involving lysoso... | ACCEPT | Summary: CHMP2B participates in MVB-lysosome fusion. Reason: Core function of ESCRT pathway in endolysosomal trafficking. Supporting Evidence: PMID:21118109 The role of ESCRT proteins in fusion events involving lysosomes, endosomes and autophagosomes. |
| GO:0005737 cytoplasm | IDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | ACCEPT | Summary: CHMP2B is detected in the cytoplasm. Reason: CHMP2B exists in both cytosolic (soluble, inactive) and membrane- associated (active) forms. Supporting Evidence: PMID:25468996 E-cadherin interactome complexity and robustness resolved by quantitative proteomics. |
| GO:0006914 autophagy | TAS PMID:24095276 Syntaxin 13, a genetic modifier of mutant CHMP2B in frontote... | ACCEPT | Summary: CHMP2B is required for autophagy; genetic modifier studies with Syntaxin 13. Reason: Well-established function of ESCRT-III in autophagy. Supporting Evidence: PMID:24095276 2013 Oct 3. Syntaxin 13, a genetic modifier of mutant CHMP2B in frontotemporal dementia, is required for autophagosome maturation. |
| GO:0000815 ESCRT III complex | TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: CHMP2B is a component of ESCRT-III complex. Reason: Core component of ESCRT-III complex. Supporting Evidence: PMID:20588296 Jun 30. Membrane budding and scission by the ESCRT machinery: it's all in the neck. |
| GO:0006914 autophagy | TAS PMID:17683935 ESCRT-III dysfunction causes autophagosome accumulation and ... | ACCEPT | Summary: CHMP2B is implicated in autophagy. Reason: Validates ESCRT-III function in autophagy. Supporting Evidence: PMID:17683935 2007 Aug 2. ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration. |
| GO:0036258 multivesicular body assembly | TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: CHMP2B participates in MVB assembly as part of ESCRT-III. Reason: Core function of ESCRT-III in MVB biogenesis. Supporting Evidence: PMID:20588296 Jun 30. Membrane budding and scission by the ESCRT machinery: it's all in the neck. |
| GO:0039702 viral budding via host ESCRT complex | TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: CHMP2B participates in viral budding via ESCRT. Reason: Well-established function of ESCRT-III. Supporting Evidence: PMID:20588296 Jun 30. Membrane budding and scission by the ESCRT machinery: it's all in the neck. |
| GO:1904903 ESCRT III complex disassembly | NAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: CHMP2B is recycled during ESCRT-III complex disassembly by VPS4. Reason: CHMP2B recruits VPS4 through its MIT-interacting motif for complex disassembly and recycling. Supporting Evidence: PMID:20588296 Jun 30. Membrane budding and scission by the ESCRT machinery: it's all in the neck. |
| GO:0000815 ESCRT III complex | TAS PMID:21118109 The role of ESCRT proteins in fusion events involving lysoso... | ACCEPT | Summary: CHMP2B is a component of ESCRT-III complex. Reason: Core component of ESCRT-III. Supporting Evidence: PMID:21118109 The role of ESCRT proteins in fusion events involving lysosomes, endosomes and autophagosomes. |
| GO:0006914 autophagy | TAS PMID:21118109 The role of ESCRT proteins in fusion events involving lysoso... | ACCEPT | Summary: CHMP2B is required for autophagy. Reason: Well-established function. Supporting Evidence: PMID:21118109 The role of ESCRT proteins in fusion events involving lysosomes, endosomes and autophagosomes. |
| GO:0005515 protein binding | IPI PMID:17683935 ESCRT-III dysfunction causes autophagosome accumulation and ... | MARK AS OVER ANNOTATED | Summary: CHMP2B interacts with CHMP2B from mouse (Q9D8B3). Reason: Protein binding is not informative. This likely reflects homodimerization or ESCRT-III assembly. Supporting Evidence: PMID:17683935 2007 Aug 2. ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration. |
| GO:0000815 ESCRT III complex | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: CHMP2B is visualized as part of ESCRT-III spirals by cryo-EM. Reason: Direct structural evidence for ESCRT-III complex membership. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding. |
| GO:0005737 cytoplasm | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: CHMP2B detected in cytoplasm by imaging. Reason: CHMP2B exists in cytoplasmic pool before membrane recruitment. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding. |
| GO:0005768 endosome | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: CHMP2B colocalizes with endosomes. Reason: Core localization for ESCRT-III function. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding. |
| GO:0019076 viral release from host cell | IMP PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in... | ACCEPT | Summary: CHMP2B is required for HIV-1 release based on depletion phenotype. Reason: Well-established function of ESCRT-III in viral budding. Supporting Evidence: PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding. |
| GO:0019076 viral release from host cell | IGI PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in... | ACCEPT | Summary: CHMP2B functions with CHMP2A and CHMP3 in viral release. Reason: Genetic interaction data supporting ESCRT-III function in viral budding. Supporting Evidence: PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding. |
| GO:0039702 viral budding via host ESCRT complex | IMP PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in... | ACCEPT | Summary: CHMP2B is required for viral budding. Reason: Direct functional evidence. Supporting Evidence: PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding. |
| GO:0070050 neuron cellular homeostasis | IMP PMID:16807408 ALS phenotypes with mutations in CHMP2B (charged multivesicu... | ACCEPT | Summary: CHMP2B mutations disrupt neuronal homeostasis, causing ALS/FTD phenotypes. Reason: Clinically validated function. CHMP2B mutations cause neurodegenerative disease through disruption of neuronal homeostasis. Supporting Evidence: PMID:16807408 Epub 2006 Jun 28. ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B). |
| GO:0005764 lysosome | IDA PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B i... | ACCEPT | Summary: CHMP2B colocalizes with lysosomes. Reason: Supports ESCRT function in endolysosomal pathway. Supporting Evidence: PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. |
| GO:0005770 late endosome | IDA PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B i... | ACCEPT | Summary: CHMP2B colocalizes with late endosomes. Reason: Core localization for ESCRT-III function. Supporting Evidence: PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. |
| GO:0005829 cytosol | IDA PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B i... | ACCEPT | Summary: CHMP2B is present in cytosol. Reason: Soluble form of CHMP2B before membrane recruitment. Supporting Evidence: PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. |
| GO:0007032 endosome organization | IMP PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B i... | ACCEPT | Summary: CHMP2B is required for endosome organization; mutations cause enlarged endosomes. Reason: Core function of ESCRT-III in endosomal compartment organization. Supporting Evidence: PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. |
| GO:0050890 cognition | IMP PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B i... | KEEP AS NON CORE | Summary: CHMP2B mutations affect cognition, causing frontotemporal dementia. 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. Supporting Evidence: PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. |
| GO:0070050 neuron cellular homeostasis | IMP PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B i... | ACCEPT | Summary: CHMP2B is required for neuronal homeostasis. Reason: Validated by disease phenotypes. ESCRT-III function is essential for neuronal health through its roles in autophagy and endolysosomal trafficking. Supporting Evidence: PMID:16041373 Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. |
| GO:0010824 regulation of centrosome duplication | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | KEEP AS NON CORE | Summary: ESCRT-III depletion affects centrosome numbers. Reason: This appears to be a secondary effect of ESCRT-III depletion rather than a direct regulatory function. The mechanism is unclear. Supporting Evidence: PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance. |
| GO:0039702 viral budding via host ESCRT complex | IGI PMID:24107264 ESCRT requirements for EIAV budding | ACCEPT | Summary: CHMP2B functions in EIAV budding via ESCRT. Reason: Extends viral budding function to other lentiviruses beyond HIV-1. Supporting Evidence: PMID:24107264 ESCRT requirements for EIAV budding. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: CHMP2B detected in exosome proteomics. 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. Supporting Evidence: PMID:23533145 2013 Apr 23. In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. |
| GO:0005515 protein binding | IPI PMID:21975012 ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate... | MARK AS OVER ANNOTATED | Summary: CHMP2B interacts with CHMP4B. Reason: Protein binding is not informative. This reflects ESCRT-III complex assembly. Supporting Evidence: PMID:21975012 ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate transmembrane cargos in hESC-derived human neurons. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: CHMP2B detected in urinary exosome proteomics. Reason: Same as above - likely co-fractionation during exosome biogenesis. Supporting Evidence: PMID:19056867 2008 Dec 3. Large-scale proteomics and phosphoproteomics of urinary exosomes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3159232 | ACCEPT | Summary: Reactome annotation for HIV virion budding machinery. Reason: CHMP2B is present in cytosol as part of viral budding pathway. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-917693 | ACCEPT | Summary: Reactome annotation for ESCRT disassembly. Reason: CHMP2B is in cytosol after VPS4-mediated disassembly. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-917700 | ACCEPT | Summary: Reactome annotation for MVB vesicle formation. Reason: CHMP2B cycles between cytosol and membrane. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668389 | ACCEPT | Summary: Reactome annotation for NE fenestration. Reason: CHMP2B is in cytosol before recruitment to NE. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668395 | ACCEPT | Summary: Reactome annotation for CHMP7-CC2D1B binding. Reason: CHMP2B is in cytosol during this pathway. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668398 | ACCEPT | Summary: Reactome annotation for CHMP7-CHMP4B binding and ESCRT-III recruitment. Reason: CHMP2B is in cytosol before membrane recruitment. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668405 | ACCEPT | Summary: Reactome annotation for spastin binding to IST1. Reason: CHMP2B is in cytosol during this pathway. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668415 | ACCEPT | Summary: Reactome annotation for VPS4-mediated ESCRT-III disassembly. Reason: CHMP2B returns to cytosol after disassembly. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668419 | ACCEPT | Summary: Reactome annotation for spastin-mediated microtubule severing. Reason: CHMP2B is in cytosol during this pathway. |
| GO:0019904 protein domain specific binding | IPI PMID:17928862 ESCRT-III recognition by VPS4 ATPases | ACCEPT | Summary: CHMP2B binds VPS4A and VPS4B through its MIT-interacting motif. Reason: Well-characterized domain-specific interaction essential for ESCRT-III recycling. Structural data confirms the MIT-MIM interaction. Supporting Evidence: PMID:17928862 ESCRT-III recognition by VPS4 ATPases. |
| GO:0180024 membrane grommet activity | NAS | NEW | Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations. Supporting Evidence: PMID:17984323 autophagic degradation is inhibited in cells depleted of ESCRT subunits and in cells expressing CHMP2B mutants |
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Download this section (compressed HTML)Q: What is the precise stoichiometry of CHMP2B within ESCRT-III polymers?
Q: How does K6 methylation by SMYD2 regulate CHMP2B polymerization dynamics?
Q: Are there tissue-specific differences in CHMP2B function that explain selective neuronal vulnerability in FTD/ALS?
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
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