CHMP4B encodes hSnf7-2, a Snf7-family core subunit of ESCRT-III. Its best-supported function is non-enzymatic ESCRT-III polymerization on endosomal/MVB and related membranes, where CHMP4B-containing filaments bend membranes and support reverse-topology budding/fission for intraluminal vesicle formation, MVB cargo sorting, and endolysosomal degradation. CHMP4B is also an important paralog for human neuronal cargo turnover/autophagosome accumulation, cytokinetic abscission, viral budding, nuclear envelope sealing, plasma membrane repair, and lens transparency, but these contexts should be interpreted through the core ESCRT-III membrane-remodeling mechanism.
Reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
Supporting Evidence:
UniProt:Q9H444
promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
Reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
Supporting Evidence:
UniProt:Q9H444
promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
Summary: True or plausible broad CHMP4B location: cytoplasmic side of plasma membrane.
Reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
Supporting Evidence:
UniProt:Q9H444
Cytoplasm. Cytosol. Late endosome membrane
UniProt:Q9H444
Membrane-associated
GO:0032511
late endosome to vacuole transport via multivesicular body sorting pathway
IBA
GO_REF:0000033
ACCEPT
Summary: Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: late endosome to vacuole transport via multivesicular body sorting pathway.
Reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9H444
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
Reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
Supporting Evidence:
UniProt:Q9H444
promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
Reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
Supporting Evidence:
UniProt:Q9H444
promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
Reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
Summary: True or plausible broad CHMP4B location: cytosol.
Reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
Reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here.
Reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
Supporting Evidence:
UniProt:Q9H444
promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
Reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function.
Supporting Evidence:
UniProt:Q9H444
Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release
CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
GO:0043162
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
IEA
GO_REF:0000117
ACCEPT
Summary: Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.
Reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9H444
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
Reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function.
Supporting Evidence:
UniProt:Q9H444
Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release
Reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here.
Reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
Reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
IPI
PMID:16189514
Towards a proteome-scale map of the human protein-protein in...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IPI
PMID:16730941
A systematic analysis of human CHMP protein interactions: ad...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IPI
PMID:16856878
CHMP7, a novel ESCRT-III-related protein, associates with CH...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IPI
PMID:17174262
HD-PTP and Alix share some membrane-traffic related proteins...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IPI
PMID:17500595
Huntingtin interacting proteins are genetic modifiers of neu...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IPI
PMID:17711858
The MIT domain of UBPY constitutes a CHMP binding and endoso...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IPI
PMID:18434552
The Bro1-related protein HD-PTP/PTPN23 is required for endos...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IPI
PMID:18511562
ALIX-CHMP4 interactions in the human ESCRT pathway.
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IPI
PMID:19523902
A crescent-shaped ALIX dimer targets ESCRT-III CHMP4 filamen...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IPI
PMID:21889351
The Phe105 loop of Alix Bro1 domain plays a key role in HIV-...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IPI
PMID:22484091
Two distinct binding modes define the interaction of Brox wi...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IPI
PMID:23051622
ESCRT-III CHMP2A and CHMP3 form variable helical polymers in...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IPI
PMID:26496610
A human interactome in three quantitative dimensions organiz...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IPI
PMID:32296183
A reference map of the human binary protein interactome.
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
Reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
Reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
Supporting Evidence:
UniProt:Q9H444
promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
Reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
IDA
PMID:24878737
Structure of cellular ESCRT-III spirals and their relationsh...
KEEP AS NON CORE
Summary: True or plausible broad CHMP4B location: plasma membrane.
Reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
Reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
Reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here.
Reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
Supporting Evidence:
UniProt:Q9H444
promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
Reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function.
Supporting Evidence:
UniProt:Q9H444
Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release
ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission
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: Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.
Reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9H444
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
Reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function.
Supporting Evidence:
UniProt:Q9H444
Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release
Reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here.
Reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
Reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
Reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here.
IPI
PMID:33349255
Lethal (2) giant discs (Lgd)/CC2D1 is required for the full ...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IMP
PMID:21975012
ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...
KEEP AS NON CORE
Summary: Supported but broad non-core CHMP4B neuronal context.
Reason: hSnf7-2/CHMP4B is required for human neuronal survival and cargo turnover, but nervous system process is broad compared with the underlying ESCRT/MVB cargo-sorting mechanism.
IPI
PMID:34818527
The ESCRT machinery counteracts Nesprin-2G-mediated mechanic...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IPI
PMID:22162750
Structure of the Bro1 domain protein BROX and functional ana...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
Reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function.
Supporting Evidence:
UniProt:Q9H444
Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release
HDA
PMID:25468996
E-cadherin interactome complexity and robustness resolved by...
MARK AS OVER ANNOTATED
Summary: Broad high-throughput/proximity annotation is not a core CHMP4B function: cadherin binding.
Reason: The E-cadherin proteomics evidence is broad proximity/localization evidence and does not establish cadherin binding or generic vesicle localization as an informative CHMP4B function.
IPI
PMID:18641129
Differential requirements for Alix and ESCRT-III in cytokine...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
Reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
IDA
PMID:25468996
E-cadherin interactome complexity and robustness resolved by...
MARK AS OVER ANNOTATED
Summary: Broad high-throughput/proximity annotation is not a core CHMP4B function: vesicle.
Reason: The E-cadherin proteomics evidence is broad proximity/localization evidence and does not establish cadherin binding or generic vesicle localization as an informative CHMP4B function.
Reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
Supporting Evidence:
UniProt:Q9H444
promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
IMP
PMID:26040712
Spastin and ESCRT-III coordinate mitotic spindle disassembly...
KEEP AS NON CORE
Summary: Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: exit from mitosis.
Reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
Supporting Evidence:
UniProt:Q9H444
promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
Reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here.
Reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
Supporting Evidence:
UniProt:Q9H444
promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
Reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
Reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function.
Supporting Evidence:
UniProt:Q9H444
Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release
Reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
IDA
PMID:17701905
CHMP4B, a novel gene for autosomal dominant cataracts linked...
KEEP AS NON CORE
Summary: True or plausible broad CHMP4B location: cytoplasm.
Reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
Reason: CHMP4B variants cause dominant cataracts and support a lens-transparency phenotype, but this phenotype does not redefine the core ESCRT-III molecular function.
IMP
PMID:20616062
Human ESCRT-III and VPS4 proteins are required for centrosom...
KEEP AS NON CORE
Summary: Supported non-core CHMP4B centrosome/spindle/cell-cycle context: regulation of centrosome duplication.
Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
UniProt:Q9H444
promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
GO:0090611
obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway
IMP
PMID:22547407
ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubi...
MODIFY
Summary: CHMP4B annotation should be replaced with a more accurate ESCRT-III term: obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway.
Reason: This obsolete ubiquitin-independent catabolic process term should be replaced by the non-obsolete MVB sorting pathway term.
Reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function.
Supporting Evidence:
UniProt:Q9H444
Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release
HDA
PMID:23533145
In-depth proteomic analyses of exosomes isolated from expres...
KEEP AS NON CORE
Summary: Plausible but broad non-core CHMP4B extracellular-exosome context.
Reason: CHMP4B/ESCRT biology supports exosome release, but high-throughput extracellular exosome localization is broad and secondary to the core ESCRT-III MVB membrane-remodeling function.
Supporting Evidence:
UniProt:Q9H444
CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IPI
PMID:21975012
ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IDA
PMID:21975012
ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...
KEEP AS NON CORE
Summary: True or plausible broad CHMP4B location: nucleus.
Reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
IDA
PMID:21975012
ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...
KEEP AS NON CORE
Summary: True or plausible broad CHMP4B location: cytoplasm.
Reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
Supporting Evidence:
UniProt:Q9H444
Cytoplasm. Cytosol. Late endosome membrane
UniProt:Q9H444
Membrane-associated
GO:0006620
post-translational protein targeting to endoplasmic reticulum membrane
IMP
PMID:21975012
ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...
REMOVE
Summary: Unsupported CHMP4B annotation: post-translational protein targeting to ER membrane.
Reason: PMID:21975012 supports hSnf7-2/CHMP4B in neuronal endosomal cargo turnover and autophagosome accumulation, but does not support a role in post-translational targeting to the ER membrane.
IDA
PMID:18209100
Plasma membrane deformation by circular arrays of ESCRT-III ...
KEEP AS NON CORE
Summary: True or plausible broad CHMP4B location: cytoplasmic side of plasma membrane.
Reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
HDA
PMID:19056867
Large-scale proteomics and phosphoproteomics of urinary exos...
KEEP AS NON CORE
Summary: Plausible but broad non-core CHMP4B extracellular-exosome context.
Reason: CHMP4B/ESCRT biology supports exosome release, but high-throughput extracellular exosome localization is broad and secondary to the core ESCRT-III MVB membrane-remodeling function.
Supporting Evidence:
UniProt:Q9H444
CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan
IPI
PMID:12860994
The ALG-2-interacting protein Alix associates with CHMP4b, a...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
HDA
PMID:20458337
MHC class II-associated proteins in B-cell exosomes and pote...
KEEP AS NON CORE
Summary: Plausible but broad non-core CHMP4B extracellular-exosome context.
Reason: CHMP4B/ESCRT biology supports exosome release, but high-throughput extracellular exosome localization is broad and secondary to the core ESCRT-III MVB membrane-remodeling function.
Supporting Evidence:
UniProt:Q9H444
CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan
IPI
PMID:21543490
Mechanism of inhibition of retrovirus release from cells by ...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
Summary: True or plausible broad CHMP4B location: cytosol.
Reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
Summary: True or plausible broad CHMP4B location: cytosol.
Reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
Summary: True or plausible broad CHMP4B location: cytosol.
Reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
Summary: True or plausible broad CHMP4B location: cytosol.
Reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
Summary: True or plausible broad CHMP4B location: cytosol.
Reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
Summary: True or plausible broad CHMP4B location: cytosol.
Reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
Summary: True or plausible broad CHMP4B location: cytosol.
Reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
Summary: True or plausible broad CHMP4B location: cytosol.
Reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
Summary: True or plausible broad CHMP4B location: cytosol.
Reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
Reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here.
IPI
PMID:20208530
PtdIns(3)P controls cytokinesis through KIF13A-mediated recr...
MARK AS OVER ANNOTATED
Summary: Over-annotated CHMP4B molecular-function annotation: protein binding.
Reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
Supporting Evidence:
UniProt:Q9H444
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9H444
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
file:human/CHMP4B/CHMP4B-notes.md
Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
IDA
PMID:18209100
Plasma membrane deformation by circular arrays of ESCRT-III ...
NEW
Summary: New CHMP4B molecular-function annotation supported by direct hSnf7-2 filament/membrane curvature evidence.
Reason: PMID:18209100 directly includes hSnf7-2/CHMP4B and shows that CHMP4-containing ESCRT-III filaments promote or stabilize negative membrane curvature and outward budding, making membrane bending activity more informative than generic binding terms.
Supporting Evidence:
UniProt:Q9H444
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
file:human/CHMP4B/CHMP4B-deep-research-falcon.md
polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
Core Functions
CHMP4B/Snf7-2 is a core ESCRT-III structural subunit that polymerizes into curved membrane-associated filaments and promotes or stabilizes negative membrane curvature for reverse-topology budding/fission.
PAR1 sorted to ILVs of MVBs through an ESCRT-III-dependent pathway independent of ubiquitination
file:human/CHMP4B/CHMP4B-deep-research-falcon.md
polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
CHMP4B/Snf7-2 contributes to proteostasis through ESCRT-dependent endolysosomal cargo turnover and autophagy/autophagosome maturation contexts; direct human-neuron knockdown causes autophagosome accumulation and altered transmembrane cargo turnover.
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex.
The MIT domain of UBPY constitutes a CHMP binding and endosomal localization signal required for efficient epidermal growth factor receptor degradation.
Comprehensive analysis of the human ESCRT-III-MIT domain interactome reveals new cofactors for cytokinetic abscission.
Reactome:R-HSA-3159232
Recruitment Of HIV Virion Budding Machinery
Reactome:R-HSA-917693
ESCRT Disassembly
Reactome:R-HSA-917700
MVB Vesicle Formation
Reactome:R-HSA-9668389
VPS4 binds ESCRT-III assemblies at nuclear envelope (NE) fenestrations
Reactome:R-HSA-9668395
CHMP7 binds CC2D1B
Reactome:R-HSA-9668398
CHMP7 binds CHMP4B, which recruits other subunits of the ESCRT-III complex
Reactome:R-HSA-9668405
SPAST (spastin) binds the IST1 subunit of ESCRT-III at the sites of microtubule attachment to chromatin
Reactome:R-HSA-9668415
VPS4 mediates disassembly of ESCRTIII subunits to promote sealing of holes in the nuclear envelope
Reactome:R-HSA-9668419
SPAST (spastin) mediates the severing of microtubules at chromosome attachment sites
file:human/CHMP4B/CHMP4B-notes.md
Local curation notes for CHMP4B
Local synthesis identifies CHMP4B/Snf7-2 ESCRT-III polymerization, membrane bending, and MVB/endolysosomal sorting as core functions, with autophagy and other ESCRT outputs retained in context.
file:human/CHMP4B/CHMP4B-deep-research-falcon.md
Falcon deep research report for CHMP4B
Falcon synthesis agrees with cached primary evidence that CHMP4B is a non-enzymatic ESCRT-III membrane-remodeling scaffold involved in reverse-topology constriction and scission.
Suggested Questions for Experts
Q: Which CHMP4 paralog is the dominant Snf7-family subunit during human phagophore closure and autophagosome maturation in endogenous cells?
Q: Should GO annotations distinguish CHMP4B direct membrane-bending/polymer function from broader ESCRT output processes such as viral budding, plasma membrane repair, nuclear envelope sealing, and cytokinetic abscission?
Q: How do CHMP4B-CHMP2B-enriched ESCRT-III assemblies differ from CHMP4A-CHMP2A assemblies in neuronal endosomal cargo turnover and proteostasis?
Suggested Experiments
Experiment: Use endogenous CHMP4B tagging plus acute depletion/rescue during starvation-induced autophagy and selective cargo turnover assays to image recruitment to phagophores, autophagosomes, amphisomes, and endosomes.
Hypothesis: If CHMP4B directly participates in autophagosome maturation or closure, it should be transiently recruited to autophagy membranes and rescue should require its polymerization/membrane-binding region.
Experiment: Compare wild-type CHMP4B with ALIX-binding, CHMP2B-interaction, and C-terminal autoinhibition mutants in MVB cargo sorting, HIV budding, cytokinetic abscission, and neuronal receptor turnover assays.
Hypothesis: CHMP4B uses the same Snf7-family filament core across ESCRT outputs, but partner and recruitment requirements differ by membrane context.
Experiment: Biochemically reconstitute CHMP4B-containing human ESCRT-III polymers with CHMP2B, CHMP3, CHMP6, and VPS4 and test membrane bending/scission on defined liposomes.
Hypothesis: CHMP4B contributes Snf7-family filament curvature that can drive membrane bending and support reverse-topology scission in a minimal human ESCRT-III module.
Deep Research
Falcon
(CHMP4B-deep-research-falcon.md)
Research Report: Human **CHMP4B** (UniProt **Q9H444**) — Functional Annotation and Current EvidenceFalconEdison Scientific Literature22 citations2 artifacts2026-06-02T07:47:48.915138
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.
Research Report: Human CHMP4B (UniProt Q9H444) — Functional Annotation and Current Evidence
The literature reviewed here is consistent with the UniProt target provided: CHMP4B (charged multivesicular body protein 4B; also referred to as Snf7/CHMP4B in the ESCRT field) is a human ESCRT-III subunit in the SNF7 family (CHMP4A/B/C). (park2024escrtiiiaversatile pages 7-8, azad2023structuralbasisof pages 1-4)
1. Key concepts and definitions (current understanding)
1.1 ESCRT machinery and “reverse-topology” membrane scission
The endosomal sorting complexes required for transport (ESCRT) are an evolutionarily conserved set of protein assemblies that remodel membranes. A defining feature of ESCRT-driven fission is reverse-topology scission: membrane constriction and cutting occurs from the cytosolic side to sever a bud neck away from the cytosol (e.g., intralumenal vesicles inside endosomes, viral budding from the plasma membrane). ESCRT-III is generally the core membrane-remodeling module that polymerizes into higher-order filaments and, together with the AAA ATPase VPS4, produces constriction and fission. (park2024escrtiiiaversatile pages 5-7, azad2023structuralbasisof pages 1-4)
1.2 What CHMP4B is (and is not)
CHMP4B is not an enzyme and does not catalyze a chemical transformation; its primary function is structural/mechanical. CHMP4-family proteins are described as SNF7-like ESCRT-III subunits that transition from an autoinhibited conformation to an open, polymerization-competent state on membranes, contributing to filament formation that bends and constricts membranes. (park2024escrtiiiaversatile pages 1-2, park2024escrtiiiaversatile pages 2-4)
1.3 Domain/family features relevant to function
CHMP4B belongs to the SNF7/CHMP4 family within ESCRT-III; this family context is repeatedly emphasized in both mechanistic reviews and structural work, and CHMP4 homologs are explicitly described as the human SNF7 family. (park2024escrtiiiaversatile pages 7-8, azad2023structuralbasisof pages 1-4)
2. Core molecular function of CHMP4B
2.1 CHMP4B as a polymerizing ESCRT-III “foundation” subunit
A 2024 ESCRT-III review synthesizes evidence that CHMP4B assembles into SNF7-like polymers and functions upstream in ESCRT-III assembly, recruiting additional ESCRT-III subunits (notably CHMP2/CHMP3 modules) as polymers mature and as fission-competent architectures are formed. (park2024escrtiiiaversatile pages 5-7, park2024escrtiiiaversatile pages 4-5)
2.2 Cooperation with VPS4 and conversion of polymers into membrane scission
ESCRT-III-mediated constriction/scission is tightly linked to VPS4: ESCRT-III polymers display C-terminal motifs that engage VPS4 (via MIT–MIM interactions), and VPS4 ATP hydrolysis is central to remodeling/disassembling ESCRT-III assemblies in a way that promotes constriction and scission. (park2024escrtiiiaversatile pages 1-2, park2024escrtiiiaversatile pages 2-4)
While Azad et al. (2023) focus experimentally on a minimal CHMP2A–CHMP3 polymer system, the paper explicitly places CHMP4 proteins (including CHMP4B) in the canonical ESCRT-III hierarchy and frames CHMP4 + CHMP2/3 + VPS4 as a minimal fission machinery concept for ESCRT-III–driven membrane cleavage. (azad2023structuralbasisof pages 1-4)
Mechanistic visual evidence (structural/biophysical): Azad et al. provide figure panels showing ESCRT-III polymer architecture and VPS4-driven cleavage of membrane-coated ESCRT-III tubes, which supports the field’s current model of ESCRT-III/VPS4 as a mechanical membrane fission system. (azad2023structuralbasisof media fc67f4f2, azad2023structuralbasisof media f34c53c8, azad2023structuralbasisof media 8f04e8c5)
3. Cellular localization and pathways involving CHMP4B
CHMP4B is repeatedly placed at endosomes/MVBs as part of ESCRT-III assemblies that sculpt intralumenal vesicles and drive scission events, consistent with its original functional context in endosomal sorting. (park2024escrtiiiaversatile pages 5-7, park2024escrtiiiaversatile pages 4-5)
ESCRT-III polymers are described as key to abscission, and the 2024 review explicitly includes CHMP4B among ESCRT-III proteins that localize to the midbody and participate in membrane constriction during cytokinesis. (park2024escrtiiiaversatile pages 7-8)
Supporting in vivo imaging evidence in 2024: Spada et al. report super-resolution imaging of CHMP4B-GFP together with ALIX and ESCRT-I (VPS28) in helical scaffolds in cells, consistent with CHMP4B’s incorporation into large ESCRT assemblies relevant to ESCRT-dependent processes including cytokinesis. (spada2024humanescrtiand pages 25-27)
3.3 Nuclear envelope (NE) reformation/repair
The 2024 ESCRT-III review summarizes evidence for ESCRT-III recruitment during nuclear envelope reformation at mitotic exit and connects CHMP4B recruitment to CHMP7-dependent pathways in this context. (park2024escrtiiiaversatile pages 7-8)
3.4 Membrane repair and organelle quality control (lysosome/plasma membrane)
The ESCRT-III review describes CHMP4B participation in membrane repair contexts, including lysosomal repair paradigms where ESCRT-III components are recruited to damaged membranes to restore compartment integrity or shed damaged membrane. (park2024escrtiiiaversatile pages 5-7, park2024escrtiiiaversatile pages 4-5)
The ESCRT-III review also discusses CHMP4B roles in autophagy-related membrane remodeling (e.g., sealing/closure steps) and connects CHMP4B to autophagy-associated processes, consistent with broader ESCRT-III roles in sealing membrane openings. (park2024escrtiiiaversatile pages 7-8)
3.6 Viral infection and virus-associated membrane remodeling
ESCRT components are often co-opted by viruses. Butt et al. (2024) describe ESCRT-III (CHMP4) and VPS4 recruitment logic and discuss viral recruitment of VPS4 and ESCRT factors in herpesvirus contexts, highlighting the broader mechanism of ESCRT engagement in viral assembly/egress (though CHMP4B is not always specified as the isoform in that excerpt). (butt2024humancytomegalovirusdeploys pages 2-3)
4. Key molecular interactions (expert synthesis)
4.1 ALIX (PDCD6IP)–CHMP4B interface
The 2024 ESCRT-III review states that ALIX binds CHMP4B (via CHMP4 C-terminal regions), positioning ALIX as an adaptor that helps recruit/organize ESCRT-III assemblies for membrane remodeling outcomes. (park2024escrtiiiaversatile pages 5-7, park2024escrtiiiaversatile pages 1-2)
4.2 CHMP6 → CHMP4B → CHMP2/CHMP3 and VPS4
The same review describes assembly logic in which CHMP6 nucleates ESCRT-III polymerization that includes CHMP4B, and then CHMP2/CHMP3 modules are recruited; VPS4 is responsible for remodeling/disassembly in the cycle. (park2024escrtiiiaversatile pages 4-5, park2024escrtiiiaversatile pages 2-4)
4.3 In vivo ESCRT scaffolds containing CHMP4B
Spada et al. (2024, preprint) provide direct in vivo imaging evidence (STED) showing CHMP4B in helical ESCRT scaffolds with ALIX and ESCRT-I (VPS28), reinforcing that CHMP4B physically participates in higher-order assemblies rather than acting as an isolated factor. (spada2024humanescrtiand pages 25-27)
5. Recent developments (prioritizing 2023–2024)
5.1 High-resolution mechanistic models for ESCRT-III–mediated membrane cleavage
A major 2023 advance is structural/biophysical work demonstrating how ESCRT-III polymers assemble and how VPS4 can trigger membrane constriction and fission in minimal systems; this work supports and constrains mechanistic models that also underlie how SNF7-family CHMP4 proteins (including CHMP4B) fit into ordered ESCRT-III assembly pathways. (azad2023structuralbasisof pages 1-4, azad2023structuralbasisof media fc67f4f2)
5.2 2024 synthesis: expanding ESCRT-III/CHMP4B roles across cell biology and disease
A 2024 review emphasizes ESCRT-III as a versatile membrane remodeling machinery and places CHMP4B across multiple processes beyond MVB formation, including cytokinesis, autophagy-related sealing, nuclear envelope dynamics, and membrane repair, reflecting current expert consensus and highlighting ongoing disease relevance.
Publication: Park et al., Animal Cells and Systems (July 2024). URL: https://doi.org/10.1080/19768354.2024.2380294 (park2024escrtiiiaversatile pages 5-7)
5.3 2024: CHMP4B requirement in coronavirus replication-center formation
Kumar et al. (2024) report that ESCRT factors, including CHMP4B, are required early in the replication cycle of human coronavirus 229E. The study reports a statistically significant reduction in viral genome levels by RT-qPCR upon CHMP4B perturbation (p = 0.024 for CHMP4B) and confirms reduced viral RNA levels by smFISH.
6. Current applications and real-world implementations
6.1 Antiviral biology and host-factor targeting logic
Real-world application is primarily mechanistic host-factor identification: CHMP4B (and ESCRT-III/VPS4 more broadly) appears as a required host machinery for certain viral steps (e.g., replication-organelle formation in HCoV-229E), motivating exploration of ESCRT-interacting steps as antiviral leverage points. (kumar2024escrtproteinvps4a pages 12-14)
6.2 Quantitative disease-target association aggregation (translational prioritization)
Open Targets aggregates evidence linking CHMP4B to disease areas, including cataract phenotypes and viral disease/HIV infection associations. While these are not clinical trials or interventions per se, they are used in drug discovery workflows for target prioritization and hypothesis generation.
Source: Open Targets platform output for CHMP4B (platform paper cited by the tool as 2025 NAR). (OpenTargets Search: -CHMP4B)
7. Disease relevance (human genetics and pathology)
7.1 Cataract genetics (strongest disease link in retrieved evidence)
Open Targets reports CHMP4B associations with early-onset non-syndromic cataract (association score 0.7111) and posterior polar cataract (score 0.6563), reflecting aggregated genetic/variant evidence and curated disease mappings in the platform. (OpenTargets Search: -CHMP4B)
7.2 Viral disease and HIV infection associations (pathway/screen-level)
Open Targets lists associations for CHMP4B with viral disease (score 0.5537) and HIV infection (score 0.4620) that are largely driven by pathway annotations and functional genetic screen evidence aggregated by the platform. (OpenTargets Search: -CHMP4B)
8. Statistics and data highlights (recent studies)
HCoV-229E replication requirement: CHMP4B perturbation reduced viral genome readouts with p = 0.024 (RT-qPCR), with supportive smFISH evidence for reduced viral RNA levels. (kumar2024escrtproteinvps4a pages 12-14)
Open Targets disease association scores: early-onset non-syndromic cataract 0.7111; posterior polar cataract 0.6563; viral disease 0.5537; HIV infection 0.4620. (OpenTargets Search: -CHMP4B)
9. Evidence map summary table
The following table compiles the key functional-annotation claims and the supporting sources.
Aspect
Concise statement
Supporting retrieved sources
Identity/domains
CHMP4B is the human charged multivesicular body protein 4B encoded by CHMP4B (UniProt Q9H444), a member of the ESCRT-III/SNF7 family. CHMP4-family proteins share the Snf7 core architecture with N-terminal membrane-interacting regions and C-terminal regulatory/MIM-containing tails that support polymerization and VPS4 engagement. (park2024escrtiiiaversatile pages 1-2, azad2023structuralbasisof pages 1-4, park2024escrtiiiaversatile pages 2-4)
Park 2024, https://doi.org/10.1080/19768354.2024.2380294; Azad 2023, https://doi.org/10.1038/s41594-022-00867-8
Core molecular function
CHMP4B is a membrane-remodeling adaptor/scaffold, not an enzyme: it polymerizes on membranes as part of ESCRT-III to drive reverse-topology membrane constriction and scission, especially during intralumenal vesicle formation and related sealing/fission reactions; VPS4 ATPase then remodels/disassembles the polymer. (park2024escrtiiiaversatile pages 5-7, park2024escrtiiiaversatile pages 1-2, azad2023structuralbasisof pages 1-4, park2024escrtiiiaversatile pages 4-5, park2024escrtiiiaversatile pages 2-4)
Park 2024, https://doi.org/10.1080/19768354.2024.2380294; Azad 2023, https://doi.org/10.1038/s41594-022-00867-8
Key interactions
CHMP4B interacts functionally with ALIX/PDCD6IP via the CHMP4 C-terminus, works sequentially with CHMP6, CHMP2A, and CHMP3 during ESCRT-III assembly, and depends on VPS4A/B for ATP-driven remodeling/disassembly; 2024 imaging also visualized CHMP4B together with ALIX and VPS28/ESCRT-I in helical scaffolds. (park2024escrtiiiaversatile pages 5-7, park2024escrtiiiaversatile pages 4-5, park2024escrtiiiaversatile pages 2-4, spada2024humanescrtiand pages 25-27, butt2024humancytomegalovirusdeploys pages 2-3)
Park 2024, https://doi.org/10.1080/19768354.2024.2380294; Spada 2024, https://doi.org/10.1101/2024.05.01.592080; Butt 2024, https://doi.org/10.1371/journal.ppat.1012300
Cellular localizations
CHMP4B functions at endosomes/MVBs, the midbody/intercellular bridge during cytokinetic abscission, the reforming nuclear envelope in mitotic exit, and some plasma-membrane/lysosomal repair contexts; recent work also places CHMP4B in membrane-remodeling assemblies relevant to viral budding and endolysosomal quality control. (park2024escrtiiiaversatile pages 5-7, park2024escrtiiiaversatile pages 7-8, park2024escrtiiiaversatile pages 4-5, spada2024humanescrtiand pages 25-27, butt2024humancytomegalovirusdeploys pages 2-3)
Park 2024, https://doi.org/10.1080/19768354.2024.2380294; Spada 2024, https://doi.org/10.1101/2024.05.01.592080; Butt 2024, https://doi.org/10.1371/journal.ppat.1012300
Park 2024, https://doi.org/10.1080/19768354.2024.2380294; Kumar 2024, https://doi.org/10.3390/covid4090095
Recent 2023-2024 developments
Recent advances include: (i) refined structural models for minimal ESCRT-III/VPS4 membrane scission machinery, which place SNF7-family CHMP4 proteins upstream of CHMP2/3 polymer maturation; (ii) 2024 super-resolution visualization of helical ESCRT-I/ALIX/CHMP4B scaffolds in vivo; and (iii) growing evidence that CHMP4B participates in autophagy-related sealing, lysosomal/endosomal repair, and coronavirus replication-center formation. (azad2023structuralbasisof pages 1-4, park2024escrtiiiaversatile pages 4-5, spada2024humanescrtiand pages 25-27, kumar2024escrtproteinvps4a pages 12-14, azad2023structuralbasisof media fc67f4f2)
Azad 2023, https://doi.org/10.1038/s41594-022-00867-8; Park 2024, https://doi.org/10.1080/19768354.2024.2380294; Spada 2024, https://doi.org/10.1101/2024.05.01.592080; Kumar 2024, https://doi.org/10.3390/covid4090095
Disease/application links
CHMP4B has the clearest human genetic disease link to cataract, including early-onset non-syndromic cataract and posterior polar cataract in Open Targets evidence aggregation. Applied/real-world relevance also comes from ESCRT dependence in viral infection, extracellular vesicle biology, and membrane-repair pathways that are being explored as therapeutic intervention points. (OpenTargets Search: -CHMP4B, kumar2024escrtproteinvps4a pages 12-14)
Open Targets query (2025 platform output for CHMP4B); Kumar 2024, https://doi.org/10.3390/covid4090095
Quantitative/assay statistics
In Open Targets, CHMP4B shows association scores of 0.7111 for early-onset non-syndromic cataract, 0.6563 for posterior polar cataract, 0.5537 for viral disease, and 0.4620 for HIV infection; in a 2024 HCoV-229E study, CHMP4B perturbation significantly reduced viral genome readouts by RT-qPCR (p = 0.024), supporting a functional requirement in coronavirus replication-center biology. (OpenTargets Search: -CHMP4B, kumar2024escrtproteinvps4a pages 12-14)
Open Targets query (2025 platform output for CHMP4B); Kumar 2024, https://doi.org/10.3390/covid4090095
Table: This table summarizes verified functional annotation for human CHMP4B/UniProt Q9H444, including identity, mechanism, localization, pathways, recent developments, and disease links. It is useful as a compact evidence map grounded in the retrieved sources.
10. Limitations of the retrieved corpus (important for interpretation)
The retrieved set contains strong mechanistic synthesis (2024 review) and several 2023–2024 mechanistic/functional studies, but it does not include a dedicated 2023–2024 human genetics primary paper directly detailing CHMP4B cataract variants; the cataract linkage here is therefore reported as platform-aggregated evidence rather than a newly read primary clinical genetics report. (OpenTargets Search: -CHMP4B)
CHMP4B-specific quantitative effect sizes beyond p-values and platform association scores were limited in the retrieved texts; additional targeted retrieval (e.g., cataract family sequencing studies or lens-cell functional work) would be required for more clinical epidemiology statistics.
Key sources (URLs and publication dates)
Park J et al. “ESCRT-III: a versatile membrane remodeling machinery and its implications in cellular processes and diseases” (Animal Cells and Systems, July 2024). https://doi.org/10.1080/19768354.2024.2380294 (park2024escrtiiiaversatile pages 5-7)
Azad K et al. “Structural basis of CHMP2A–CHMP3 ESCRT-III polymer assembly and membrane cleavage” (Nature Structural & Molecular Biology, Jan 2023). https://doi.org/10.1038/s41594-022-00867-8 (azad2023structuralbasisof pages 1-4)
Spada SJ et al. “Human ESCRT-I and ALIX function as scaffolding helical filaments in vivo” (bioRxiv, May 2024). https://doi.org/10.1101/2024.05.01.592080 (spada2024humanescrtiand pages 25-27)
Kumar R et al. “ESCRT Protein VPS4A Is Required for the Formation of Replication Centers and Replication of Human Coronavirus 229E (HCoV-229E)” (COVID, Aug 2024). https://doi.org/10.3390/covid4090095 (kumar2024escrtproteinvps4a pages 12-14)
Butt BG et al. “Human cytomegalovirus deploys molecular mimicry to recruit VPS4A to sites of virus assembly” (PLOS Pathogens, Jan 2024). https://doi.org/10.1371/journal.ppat.1012300 (butt2024humancytomegalovirusdeploys pages 2-3)
Open Targets Platform CHMP4B disease association output (tool-retrieved; platform paper referenced by tool: Nucleic Acids Research, 2025). https://platform.opentargets.org/ (OpenTargets Search: -CHMP4B)
References
(park2024escrtiiiaversatile pages 7-8): Jisoo Park, Jongyoon Kim, Hyungsun Park, Taewan Kim, and Seongju Lee. Escrt-iii: a versatile membrane remodeling machinery and its implications in cellular processes and diseases. Animal Cells and Systems, 28:367-380, Jul 2024. URL: https://doi.org/10.1080/19768354.2024.2380294, doi:10.1080/19768354.2024.2380294. This article has 14 citations and is from a peer-reviewed journal.
(azad2023structuralbasisof pages 1-4): Kimi Azad, Delphine Guilligay, Cecile Boscheron, Sourav Maity, Nicola De Franceschi, Guidenn Sulbaran, Gregory Effantin, Haiyan Wang, Jean-Philippe Kleman, Patricia Bassereau, Guy Schoehn, Wouter H. Roos, Ambroise Desfosses, and Winfried Weissenhorn. Structural basis of chmp2a–chmp3 escrt-iii polymer assembly and membrane cleavage. Nature Structural & Molecular Biology, 30:81-90, Jan 2023. URL: https://doi.org/10.1038/s41594-022-00867-8, doi:10.1038/s41594-022-00867-8. This article has 66 citations and is from a highest quality peer-reviewed journal.
(park2024escrtiiiaversatile pages 5-7): Jisoo Park, Jongyoon Kim, Hyungsun Park, Taewan Kim, and Seongju Lee. Escrt-iii: a versatile membrane remodeling machinery and its implications in cellular processes and diseases. Animal Cells and Systems, 28:367-380, Jul 2024. URL: https://doi.org/10.1080/19768354.2024.2380294, doi:10.1080/19768354.2024.2380294. This article has 14 citations and is from a peer-reviewed journal.
(park2024escrtiiiaversatile pages 1-2): Jisoo Park, Jongyoon Kim, Hyungsun Park, Taewan Kim, and Seongju Lee. Escrt-iii: a versatile membrane remodeling machinery and its implications in cellular processes and diseases. Animal Cells and Systems, 28:367-380, Jul 2024. URL: https://doi.org/10.1080/19768354.2024.2380294, doi:10.1080/19768354.2024.2380294. This article has 14 citations and is from a peer-reviewed journal.
(park2024escrtiiiaversatile pages 2-4): Jisoo Park, Jongyoon Kim, Hyungsun Park, Taewan Kim, and Seongju Lee. Escrt-iii: a versatile membrane remodeling machinery and its implications in cellular processes and diseases. Animal Cells and Systems, 28:367-380, Jul 2024. URL: https://doi.org/10.1080/19768354.2024.2380294, doi:10.1080/19768354.2024.2380294. This article has 14 citations and is from a peer-reviewed journal.
(park2024escrtiiiaversatile pages 4-5): Jisoo Park, Jongyoon Kim, Hyungsun Park, Taewan Kim, and Seongju Lee. Escrt-iii: a versatile membrane remodeling machinery and its implications in cellular processes and diseases. Animal Cells and Systems, 28:367-380, Jul 2024. URL: https://doi.org/10.1080/19768354.2024.2380294, doi:10.1080/19768354.2024.2380294. This article has 14 citations and is from a peer-reviewed journal.
(azad2023structuralbasisof media fc67f4f2): Kimi Azad, Delphine Guilligay, Cecile Boscheron, Sourav Maity, Nicola De Franceschi, Guidenn Sulbaran, Gregory Effantin, Haiyan Wang, Jean-Philippe Kleman, Patricia Bassereau, Guy Schoehn, Wouter H. Roos, Ambroise Desfosses, and Winfried Weissenhorn. Structural basis of chmp2a–chmp3 escrt-iii polymer assembly and membrane cleavage. Nature Structural & Molecular Biology, 30:81-90, Jan 2023. URL: https://doi.org/10.1038/s41594-022-00867-8, doi:10.1038/s41594-022-00867-8. This article has 66 citations and is from a highest quality peer-reviewed journal.
(azad2023structuralbasisof media f34c53c8): Kimi Azad, Delphine Guilligay, Cecile Boscheron, Sourav Maity, Nicola De Franceschi, Guidenn Sulbaran, Gregory Effantin, Haiyan Wang, Jean-Philippe Kleman, Patricia Bassereau, Guy Schoehn, Wouter H. Roos, Ambroise Desfosses, and Winfried Weissenhorn. Structural basis of chmp2a–chmp3 escrt-iii polymer assembly and membrane cleavage. Nature Structural & Molecular Biology, 30:81-90, Jan 2023. URL: https://doi.org/10.1038/s41594-022-00867-8, doi:10.1038/s41594-022-00867-8. This article has 66 citations and is from a highest quality peer-reviewed journal.
(azad2023structuralbasisof media 8f04e8c5): Kimi Azad, Delphine Guilligay, Cecile Boscheron, Sourav Maity, Nicola De Franceschi, Guidenn Sulbaran, Gregory Effantin, Haiyan Wang, Jean-Philippe Kleman, Patricia Bassereau, Guy Schoehn, Wouter H. Roos, Ambroise Desfosses, and Winfried Weissenhorn. Structural basis of chmp2a–chmp3 escrt-iii polymer assembly and membrane cleavage. Nature Structural & Molecular Biology, 30:81-90, Jan 2023. URL: https://doi.org/10.1038/s41594-022-00867-8, doi:10.1038/s41594-022-00867-8. This article has 66 citations and is from a highest quality peer-reviewed journal.
(spada2024humanescrtiand pages 25-27): Stephanie J. Spada, Kevin M. Rose, Paola Sette, Sarah K. O’Connor, Vincent Dussupt, V. Siddartha Yerramilli, Kunio Nagashima, Virginie Helle Sjoelund, Phillip Cruz, Juraj Kabat, Sundar Ganesan, Margery Smelkinson, Aleksandra Nita-Lazar, Forrest Hoyt, Suzanne Scarlata, Vanessa Hirsch, Sonja M. Best, Michael E. Grigg, and Fadila Bouamr. Human escrt-i and alix function as scaffolding helical filaments in vivo. bioRxiv, May 2024. URL: https://doi.org/10.1101/2024.05.01.592080, doi:10.1101/2024.05.01.592080. This article has 1 citations.
(butt2024humancytomegalovirusdeploys pages 2-3): Benjamin G. Butt, Daniela Fischer, Alison R. Rep, Martin Schauflinger, Clarissa Read, Thomas Böck, Manuel Hirner, Stephen C. Graham, and Jens von Einem. Human cytomegalovirus deploys molecular mimicry to recruit vps4a to sites of virus assembly. PLOS Pathogens, Jan 2024. URL: https://doi.org/10.1371/journal.ppat.1012300, doi:10.1371/journal.ppat.1012300. This article has 6 citations and is from a highest quality peer-reviewed journal.
(kumar2024escrtproteinvps4a pages 12-14): Rinki Kumar, Rebecca Kaddis Maldonado, Neil D. Christensen, Maria C. Bewley, John M. Flanagan, Nicholas J. Buchkovich, and Leslie J. Parent. Escrt protein vps4a is required for the formation of replication centers and replication of human coronavirus 229e (hcov-229e). COVID, 4:1338-1354, Aug 2024. URL: https://doi.org/10.3390/covid4090095, doi:10.3390/covid4090095. This article has 0 citations.
(OpenTargets Search: -CHMP4B): Open Targets Query (-CHMP4B, 8 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
Falcon deep research was started with just deep-research-falcon human CHMP4B; the wrapper printed Timeout: 600s, but it produced CHMP4B-deep-research-falcon.md with a completed report and 22 citations. I used it as synthesis context only where it agreed with cached primary evidence, especially its summary that CHMP4B is an ESCRT-III membrane-remodeling scaffold rather than an enzyme [file:human/CHMP4B/CHMP4B-deep-research-falcon.md "polymerizes on membranes as part of ESCRT-III to drive reverse-topology membrane constriction and scission"].
CHMP4B encodes hSnf7-2, a Snf7-family core ESCRT-III subunit. UniProt summarizes it as a probable ESCRT-III core component involved in MVB formation, endosomal cargo sorting, membrane fission, cytokinesis, nuclear envelope sealing, and exosomal release [UniProt:Q9H444 "Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)"; UniProt:Q9H444 "involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs"; UniProt:Q9H444 "believed to mediate the necessary vesicle extrusion and/or membrane fission activities"].
The strongest direct mechanistic evidence for the molecular function is ESCRT-III filament formation and membrane curvature. Hanson et al. explicitly examined hSnf7-1/CHMP4A and hSnf7-2/CHMP4B and found that both assemble into approximately 5 nm curved filaments, create circular arrays, and promote/stabilize negative membrane curvature and outward budding [PMID:18209100 "hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)"; PMID:18209100 "assemble into regular approximately 5-nm filaments that curve and self-associate"; PMID:18209100 "form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding"]. This supports adding membrane bending activity, and supports retaining protein polymerization and membrane fission while replacing generic identical protein binding/homodimerization with more informative terms.
CHMP4B has direct evidence in endosomal/MVB sorting. The original ALIX paper identified CHMP4B as a human Snf7 homolog involved in MVB sorting, found ALIX-CHMP4B interaction, and localized CHMP4B to early/late endosomal puncta [PMID:12860994 "The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting"; PMID:12860994 "CHMP4b transiently expressed in HeLa cells mainly exhibited a punctate cytoplasmic pattern"; PMID:12860994 "partly overlapped the distributions of early and late endosome markers"]. CHMP6 work provides additional support for CHMP4B interaction in mammalian ESCRT-III assembly and endosomal cargo sorting [PMID:15511219 "interacts directly with another ESCRT-III component CHMP4b/Shax"; PMID:15511219 "CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting"].
CHMP4B is stronger than CHMP4A for several ESCRT output contexts. In the CHMP4C abscission checkpoint paper, depletion of CHMP4B, but not CHMP4A or CHMP4C, prevented MHC-I degradation, inhibited HIV-1 release, and blocked completion of cytokinesis; GFP-CHMP4B localized transiently to midbody arms just before abscission [PMID:22422861 "depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect"; PMID:22422861 "only depletion of CHMP4B inhibited this ESCRT-dependent process"; PMID:22422861 "CHMP4B was again the sole paralog required"; PMID:22422861 "GFP-CHMP4B localized transiently to the midbody arms immediately"]. These are valid non-core ESCRT scission roles in this PN-focused review.
Autophagy annotations are retained as PN-relevant endolysosomal/autophagy context rather than treated as the only core function. General ESCRT/MVB work shows ESCRT depletion inhibits autophagic degradation and causes autophagosome/amphisome accumulation [PMID:17984323 "autophagic degradation is inhibited in cells depleted of ESCRT subunits"; PMID:17984323 "Functional multivesicular bodies are required for autophagic clearance"]. Human neuron work directly implicates hSnf7-2/CHMP4B: hSnf7-2 is abundant in human neurons, required for neuronal survival, preferentially associates with CHMP2B, regulates transmembrane cargo turnover, and hSnf7-2 knockdown causes GFP-LC3 autophagosome accumulation [PMID:21975012 "hSnf7-1 and hSnf7-2 are most abundantly expressed in human neurons"; PMID:21975012 "hSnf7-2 are required for the survival of human neurons"; PMID:21975012 "complexes containing hSnf7-2 and CHMP2B were more abundant"; PMID:21975012 "SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation"]. The STX13 paper is useful PN context for ESCRT-III dysfunction and phagophore/autophagosome maturation, but it is mainly about STX13/Vti1a and mutant CHMP2B, not a direct CHMP4B assay PMID:24095276.
Other retained non-core contexts include plasma membrane repair [PMID:24482116 "ESCRT proteins were recruited within seconds to plasma membrane wounds"; PMID:24482116 "repair of certain wounds is ensured by ESCRT-mediated extracellular shedding"], nuclear envelope sealing/reassembly with SPAST [UniProt:Q9H444 "promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase"; PMID:26040712 "Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing"], viral budding/HIV release [PMID:24878737 "ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission"; PMID:24878737 "viral budding and cytokinesis"], and lens transparency as a disease/phenotype context rather than core molecular function [PMID:17701905 "CHMP4B, which encodes a key component of the endosome sorting complex required for transport-III (ESCRT-III) system"; PMID:17701905 "plays a vital role in the maintenance of lens transparency"].
Several annotations are over-annotated or unsupported. Generic protein binding rows do not capture CHMP4B function and are marked over-annotated. Cadherin binding and vesicle annotations from the E-cadherin proximity proteomics study are broad high-throughput proximity/localization findings, not core CHMP4B molecular function PMID:25468996. The ER membrane targeting annotation from PMID:21975012 is removed because the paper supports CHMP4B/Snf7-2 in neuronal cargo turnover/autophagosome accumulation, not post-translational targeting to the ER membrane.
Pn Notes
(CHMP4B-pn-notes.md)
CHMP4B PN Consistency Notes
Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
Description: CHMP4B encodes hSnf7-2, a Snf7-family core subunit of ESCRT-III. Its best-supported function is non-enzymatic ESCRT-III polymerization on endosomal/MVB and related membranes, where CHMP4B-containing filaments bend membranes and support reverse-topology budding/fission for intraluminal vesicle formation, MVB cargo sorting, and endolysosomal degradation. CHMP4B is also an important paralog for human neuronal cargo turnover/autophagosome accumulation, cytokinetic abscission, viral budding, nuclear envelope sealing, plasma membrane repair, and lens transparency, but these contexts should be interpreted through the core ESCRT-III membrane-remodeling mechanism.
Consistency: Strong. Deep-research (falcon), review, PN, and mapping all agree CHMP4B is the dominant Snf7-family ESCRT-III core subunit with a genuine, gene-specific autophagy link: human-neuron hSnf7-2 knockdown causes autophagosome accumulation (PMID:21975012); STX13/phagophore→autophagosome maturation (PMID:24095276). No contradictions.
PN story / NEW pressure: PN's "Sealing of autophagophore" projects GO:0000045 autophagosome assembly (verified real via OLS) as more specific than current GOA. The review captures the autophagy axis at a sibling altitude — GO:0097352 autophagosome maturation + GO:0016236 macroautophagy (both KEEP_AS_NON_CORE, in core_functions) — but does NOT carry GO:0000045. For CHMP4B specifically, the closure/sealing role is the best-supported of the five paralogs, so GO:0000045 is a defensible ADD as non-core. ADD GO:0000045 autophagosome assembly (non-core).
Evidence alignment: Partial. PN cites two reviews (Cells "Key Regulators of Autophagosome Closure"; tandfonline mitophagy sealing). Review cites primary literature (PMID:18209100, 21975012, 17984323, 24095276) — same ESCRT-in-autophagy theme, different specific papers. GO:0000815 IBA original_reference is GO_REF:0000033, not the PN review.
Verdict: Consistent; well-handled. Recommended edits: add GO:0000045 autophagosome assembly as a NEW non-core annotation (PMID:21975012, 24095276) to close the one gap vs the PN projection.
PN placement:ALP → Autophagosome closure maturation and lysosome fusion → Sealing of autophagophore membrane → ESCRT-III complex component AND ALP → Microautophagy → General microautophagy machinery → ESCRT-III complex component (2 rows)
PN-node mapping: type = mapped/ok_for_propagation → GO:0000815 ESCRT III complex (already in GOA); "Sealing" group = mapped → GO:0000045 autophagosome assembly (more_specific_than_existing_goa); both classes context_only/too_broad (GO:0016236 macroautophagy, GO:0016237 microautophagy); branch no_mapping.
Consistency: Strong. Deep-research (falcon), review, PN, and mapping all agree CHMP4B is the dominant Snf7-family ESCRT-III core subunit with a genuine, gene-specific autophagy link: human-neuron hSnf7-2 knockdown causes autophagosome accumulation (PMID:21975012); STX13/phagophore→autophagosome maturation (PMID:24095276). No contradictions.
PN story / NEW pressure: PN's "Sealing of autophagophore" projects GO:0000045 autophagosome assembly (verified real via OLS) as more specific than current GOA. The review captures the autophagy axis at a sibling altitude — GO:0097352 autophagosome maturation + GO:0016236 macroautophagy (both KEEP_AS_NON_CORE, in core_functions) — but does NOT carry GO:0000045. For CHMP4B specifically, the closure/sealing role is the best-supported of the five paralogs, so GO:0000045 is a defensible ADD as non-core. ADD GO:0000045 autophagosome assembly (non-core).
Mapping strategy: No change needed. CHMP4B membership reinforces (does not alter) the leaf→GO:0000815 / group→GO:0000045 calls; the conservative class-level context_only holds. PN projection is appropriately narrower than the existing macroautophagy term, unlike the rejected TOMM20/HSPA8/RAB7A broader projections.
Evidence alignment: Partial. PN cites two reviews (Cells "Key Regulators of Autophagosome Closure"; tandfonline mitophagy sealing). Review cites primary literature (PMID:18209100, 21975012, 17984323, 24095276) — same ESCRT-in-autophagy theme, different specific papers. GO:0000815 IBA original_reference is GO_REF:0000033, not the PN review.
Verdict: Consistent; well-handled. Recommended edits: add GO:0000045 autophagosome assembly as a NEW non-core annotation (PMID:21975012, 24095276) to close the one gap vs the PN projection.
Full article: ESCRT-mediated phagophore sealing during mitophagy (tandfonline.com)
PN-node mapping records (path + ancestors):
[type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-III complex component
status=mapped scope=ok_for_propagation_to_go GO=[GO:0000815 ESCRT III complex]
rationale: This PN type is a structural component class for ESCRT-III factors used in autophagophore sealing. The matching GO cellular-component term is ESCRT III complex, which is more precise than the broader late-fusion process mapping.
[group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
status=mapped scope=ok_for_propagation_to_go GO=[GO:0000045 autophagosome assembly]
rationale: This group captures autophagophore closure/sealing, a late step in autophagosome assembly. Autophagosome assembly is the safer process target than autophagosome-lysosome fusion.
[class] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion
status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
rationale: This class is a late macroautophagy context, but the subtree mixes docking, fusion, localization, membrane-composition, and unknown late-stage roles. The class-level relation is useful for display while propagation is restricted to narrower mechanism nodes.
[branch] Autophagy-Lysosome Pathway
status=no_mapping scope= GO=[]
rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.
[type] Autophagy-Lysosome Pathway|Microautophagy|General microautophagy machinery|ESCRT-III complex component
status=mapped scope=ok_for_propagation_to_go GO=[GO:0000815 ESCRT III complex]
rationale: This leaf is a component bucket for ESCRT-III machinery used in microautophagy contexts. The shared GO assertion is ESCRT III complex membership.
[group] Autophagy-Lysosome Pathway|Microautophagy|General microautophagy machinery
status=no_mapping scope= GO=[]
rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
[class] Autophagy-Lysosome Pathway|Microautophagy
status=context_only scope=too_broad_to_propagate GO=[GO:0016237 microautophagy]
rationale: The class names a real GO process, but the subtree includes machinery components and mitochondrion-derived-vesicle contexts as well as process labels. Propagation is restricted to narrower nodes.
[branch] Autophagy-Lysosome Pathway
status=no_mapping scope= GO=[]
rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.
Projected GO annotations (3)
GO:0000045 autophagosome assembly | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
GO:0000815 ESCRT III complex | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-III complex component
This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.
📄 View Raw YAML
id: Q9H444
gene_symbol: CHMP4B
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: CHMP4B encodes hSnf7-2, a Snf7-family core subunit of ESCRT-III. Its best-supported function is non-enzymatic ESCRT-III polymerization on endosomal/MVB and related membranes, where CHMP4B-containing filaments bend membranes and support reverse-topology budding/fission for intraluminal vesicle formation, MVB cargo sorting, and endolysosomal degradation. CHMP4B is also an important paralog for human neuronal cargo turnover/autophagosome accumulation, cytokinetic abscission, viral budding, nuclear envelope sealing, plasma membrane repair, and lens transparency, but these contexts should be interpreted through the core ESCRT-III membrane-remodeling mechanism.
existing_annotations:
- term:
id: GO:0005635
label: nuclear envelope
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear envelope.'
action: KEEP_AS_NON_CORE
reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- reference_id: PMID:26040712
supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly
- reference_id: PMID:26040713
supporting_text: GFP-CHMP4B transiently localises to telophase nuclei
- term:
id: GO:0031468
label: nuclear membrane reassembly
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear membrane reassembly.'
action: KEEP_AS_NON_CORE
reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- reference_id: PMID:26040712
supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly
- reference_id: PMID:26040713
supporting_text: GFP-CHMP4B transiently localises to telophase nuclei
- term:
id: GO:0000815
label: ESCRT III complex
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: part_of
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0009898
label: cytoplasmic side of plasma membrane
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: 'True or plausible broad CHMP4B location: cytoplasmic side of plasma membrane.'
action: KEEP_AS_NON_CORE
reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Cytoplasm. Cytosol. Late endosome membrane
- reference_id: UniProt:Q9H444
supporting_text: Membrane-associated
- term:
id: GO:0032511
label: late endosome to vacuole transport via multivesicular body sorting pathway
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: late endosome to vacuole transport via multivesicular body sorting pathway.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0000776
label: kinetochore
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: located_in
review:
summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: kinetochore.'
action: KEEP_AS_NON_CORE
reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
supported_by:
- reference_id: PMID:20616062
supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers
- reference_id: PMID:20616062
supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- term:
id: GO:0001778
label: plasma membrane repair
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: Supported non-core CHMP4B plasma-membrane repair context.
action: KEEP_AS_NON_CORE
reason: Plasma membrane repair is a valid topologically related ESCRT output, but it is secondary to the core MVB/endosomal ESCRT-III function.
supported_by:
- reference_id: PMID:24482116
supporting_text: ESCRT proteins were recruited within seconds to plasma membrane wounds
- reference_id: PMID:24482116
supporting_text: repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- term:
id: GO:0005635
label: nuclear envelope
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear envelope.'
action: KEEP_AS_NON_CORE
reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- reference_id: PMID:26040712
supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly
- reference_id: PMID:26040713
supporting_text: GFP-CHMP4B transiently localises to telophase nuclei
- term:
id: GO:0005643
label: nuclear pore
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: part_of
review:
summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear pore.'
action: KEEP_AS_NON_CORE
reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- reference_id: PMID:26040712
supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly
- reference_id: PMID:26040713
supporting_text: GFP-CHMP4B transiently localises to telophase nuclei
- term:
id: GO:0005765
label: lysosomal membrane
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: located_in
review:
summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: lysosomal membrane.'
action: ACCEPT
reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
supported_by:
- reference_id: PMID:21975012
supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation
- reference_id: PMID:21975012
supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A
- reference_id: PMID:17984323
supporting_text: Functional multivesicular bodies are required for autophagic clearance
- reference_id: PMID:17984323
supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0005828
label: kinetochore microtubule
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: located_in
review:
summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: kinetochore microtubule.'
action: KEEP_AS_NON_CORE
reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
supported_by:
- reference_id: PMID:20616062
supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers
- reference_id: PMID:20616062
supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- term:
id: GO:0005829
label: cytosol
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: 'True or plausible broad CHMP4B location: cytosol.'
action: KEEP_AS_NON_CORE
reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Cytoplasm. Cytosol. Late endosome membrane
- reference_id: UniProt:Q9H444
supporting_text: Membrane-associated
- term:
id: GO:0007034
label: vacuolar transport
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: involved_in
review:
summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: vacuolar transport.'
action: MODIFY
reason: Multivesicular body sorting is the informative ESCRT-III process; vacuolar transport is too broad for human CHMP4B.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
proposed_replacement_terms:
- id: GO:0071985
label: multivesicular body sorting pathway
- term:
id: GO:0007080
label: mitotic metaphase chromosome alignment
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: mitotic metaphase chromosome alignment.'
action: KEEP_AS_NON_CORE
reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
supported_by:
- reference_id: PMID:20616062
supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers
- reference_id: PMID:20616062
supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- term:
id: GO:0030496
label: midbody
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: located_in
review:
summary: 'Supported non-core CHMP4B cytokinesis/abscission context: midbody.'
action: KEEP_AS_NON_CORE
reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here.
supported_by:
- reference_id: PMID:22422861
supporting_text: CHMP4B was again the sole paralog required
- reference_id: PMID:22422861
supporting_text: GFP-CHMP4B localized transiently to the midbody arms immediately
- reference_id: PMID:21310966
supporting_text: ESCRT-III co-localized with constriction zones and was required for assembly of 17-nanometer-diameter filaments
- reference_id: UniProt:Q9H444
supporting_text: functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis
- term:
id: GO:0031468
label: nuclear membrane reassembly
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear membrane reassembly.'
action: KEEP_AS_NON_CORE
reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- reference_id: PMID:26040712
supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly
- reference_id: PMID:26040713
supporting_text: GFP-CHMP4B transiently localises to telophase nuclei
- term:
id: GO:0031902
label: late endosome membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: late endosome membrane.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0032585
label: multivesicular body membrane
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: located_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: multivesicular body membrane.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0036258
label: multivesicular body assembly
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0039702
label: viral budding via host ESCRT complex
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B viral budding context: viral budding via host ESCRT complex.'
action: KEEP_AS_NON_CORE
reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release
- reference_id: PMID:22422861
supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process
- reference_id: PMID:24878737
supporting_text: ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission
- term:
id: GO:0042803
label: protein homodimerization activity
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: enables
review:
summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: protein homodimerization activity.'
action: MODIFY
reason: Homodimerization is less informative than CHMP4B/Snf7-family polymerization and membrane bending.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
proposed_replacement_terms:
- id: GO:0051258
label: protein polymerization
- id: GO:0180020
label: membrane bending activity
- 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
qualifier: involved_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0046761
label: viral budding from plasma membrane
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B viral budding context: viral budding from plasma membrane.'
action: KEEP_AS_NON_CORE
reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release
- reference_id: PMID:22422861
supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process
- reference_id: PMID:24878737
supporting_text: ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission
- term:
id: GO:0061952
label: midbody abscission
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B cytokinesis/abscission context: midbody abscission.'
action: KEEP_AS_NON_CORE
reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here.
supported_by:
- reference_id: PMID:22422861
supporting_text: CHMP4B was again the sole paralog required
- reference_id: PMID:22422861
supporting_text: GFP-CHMP4B localized transiently to the midbody arms immediately
- reference_id: PMID:21310966
supporting_text: ESCRT-III co-localized with constriction zones and was required for assembly of 17-nanometer-diameter filaments
- reference_id: UniProt:Q9H444
supporting_text: functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis
- term:
id: GO:0071985
label: multivesicular body sorting pathway
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0097352
label: autophagosome maturation
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: autophagosome maturation.'
action: ACCEPT
reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
supported_by:
- reference_id: PMID:21975012
supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation
- reference_id: PMID:21975012
supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A
- reference_id: PMID:17984323
supporting_text: Functional multivesicular bodies are required for autophagic clearance
- reference_id: PMID:17984323
supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:1901673
label: regulation of mitotic spindle assembly
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: regulation of mitotic spindle assembly.'
action: KEEP_AS_NON_CORE
reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
supported_by:
- reference_id: PMID:20616062
supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers
- reference_id: PMID:20616062
supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- term:
id: GO:1902774
label: late endosome to lysosome transport
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: late endosome to lysosome transport.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:1904930
label: amphisome membrane
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: located_in
review:
summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: amphisome membrane.'
action: ACCEPT
reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
supported_by:
- reference_id: PMID:21975012
supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation
- reference_id: PMID:21975012
supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A
- reference_id: PMID:17984323
supporting_text: Functional multivesicular bodies are required for autophagic clearance
- reference_id: PMID:17984323
supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:16189514
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:16730941
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:16856878
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:17174262
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:17500595
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:17711858
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:18434552
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:18511562
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19523902
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:21889351
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22484091
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23051622
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:26496610
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:32296183
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:32814053
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:35271311
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:16730941
qualifier: enables
review:
summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: identical protein binding.'
action: MODIFY
reason: Identical protein binding is less informative than CHMP4B/Snf7-family polymerization and membrane bending.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
proposed_replacement_terms:
- id: GO:0051258
label: protein polymerization
- id: GO:0180020
label: membrane bending activity
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:19523902
qualifier: enables
review:
summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: identical protein binding.'
action: MODIFY
reason: Identical protein binding is less informative than CHMP4B/Snf7-family polymerization and membrane bending.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
proposed_replacement_terms:
- id: GO:0051258
label: protein polymerization
- id: GO:0180020
label: membrane bending activity
- term:
id: GO:0000421
label: autophagosome membrane
evidence_type: IDA
original_reference_id: PMID:17984323
qualifier: located_in
review:
summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: autophagosome membrane.'
action: ACCEPT
reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
supported_by:
- reference_id: PMID:21975012
supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation
- reference_id: PMID:21975012
supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A
- reference_id: PMID:17984323
supporting_text: Functional multivesicular bodies are required for autophagic clearance
- reference_id: PMID:17984323
supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0000776
label: kinetochore
evidence_type: IDA
original_reference_id: PMID:26040712
qualifier: located_in
review:
summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: kinetochore.'
action: KEEP_AS_NON_CORE
reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
supported_by:
- reference_id: PMID:20616062
supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers
- reference_id: PMID:20616062
supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- term:
id: GO:0000815
label: ESCRT III complex
evidence_type: NAS
original_reference_id: PMID:36107470
qualifier: part_of
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0001778
label: plasma membrane repair
evidence_type: IDA
original_reference_id: PMID:24482116
qualifier: involved_in
review:
summary: Supported non-core CHMP4B plasma-membrane repair context.
action: KEEP_AS_NON_CORE
reason: Plasma membrane repair is a valid topologically related ESCRT output, but it is secondary to the core MVB/endosomal ESCRT-III function.
supported_by:
- reference_id: PMID:24482116
supporting_text: ESCRT proteins were recruited within seconds to plasma membrane wounds
- reference_id: PMID:24482116
supporting_text: repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- term:
id: GO:0005643
label: nuclear pore
evidence_type: IDA
original_reference_id: PMID:26040713
qualifier: part_of
review:
summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear pore.'
action: KEEP_AS_NON_CORE
reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- reference_id: PMID:26040712
supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly
- reference_id: PMID:26040713
supporting_text: GFP-CHMP4B transiently localises to telophase nuclei
- term:
id: GO:0005765
label: lysosomal membrane
evidence_type: IDA
original_reference_id: PMID:17984323
qualifier: located_in
review:
summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: lysosomal membrane.'
action: ACCEPT
reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
supported_by:
- reference_id: PMID:21975012
supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation
- reference_id: PMID:21975012
supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A
- reference_id: PMID:17984323
supporting_text: Functional multivesicular bodies are required for autophagic clearance
- reference_id: PMID:17984323
supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0005828
label: kinetochore microtubule
evidence_type: IDA
original_reference_id: PMID:26040712
qualifier: located_in
review:
summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: kinetochore microtubule.'
action: KEEP_AS_NON_CORE
reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
supported_by:
- reference_id: PMID:20616062
supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers
- reference_id: PMID:20616062
supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:24878737
qualifier: located_in
review:
summary: 'True or plausible broad CHMP4B location: plasma membrane.'
action: KEEP_AS_NON_CORE
reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Cytoplasm. Cytosol. Late endosome membrane
- reference_id: UniProt:Q9H444
supporting_text: Membrane-associated
- term:
id: GO:0006914
label: autophagy
evidence_type: IMP
original_reference_id: PMID:17984323
qualifier: involved_in
review:
summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: autophagy.'
action: ACCEPT
reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
supported_by:
- reference_id: PMID:21975012
supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation
- reference_id: PMID:21975012
supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A
- reference_id: PMID:17984323
supporting_text: Functional multivesicular bodies are required for autophagic clearance
- reference_id: PMID:17984323
supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0006997
label: nucleus organization
evidence_type: IMP
original_reference_id: PMID:20616062
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: nucleus organization.'
action: KEEP_AS_NON_CORE
reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
supported_by:
- reference_id: PMID:20616062
supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers
- reference_id: PMID:20616062
supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- term:
id: GO:0007080
label: mitotic metaphase chromosome alignment
evidence_type: IMP
original_reference_id: PMID:20616062
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: mitotic metaphase chromosome alignment.'
action: KEEP_AS_NON_CORE
reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
supported_by:
- reference_id: PMID:20616062
supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers
- reference_id: PMID:20616062
supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- term:
id: GO:0030496
label: midbody
evidence_type: IDA
original_reference_id: PMID:26040712
qualifier: located_in
review:
summary: 'Supported non-core CHMP4B cytokinesis/abscission context: midbody.'
action: KEEP_AS_NON_CORE
reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here.
supported_by:
- reference_id: PMID:22422861
supporting_text: CHMP4B was again the sole paralog required
- reference_id: PMID:22422861
supporting_text: GFP-CHMP4B localized transiently to the midbody arms immediately
- reference_id: PMID:21310966
supporting_text: ESCRT-III co-localized with constriction zones and was required for assembly of 17-nanometer-diameter filaments
- reference_id: UniProt:Q9H444
supporting_text: functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis
- term:
id: GO:0031468
label: nuclear membrane reassembly
evidence_type: IMP
original_reference_id: PMID:26040713
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear membrane reassembly.'
action: KEEP_AS_NON_CORE
reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- reference_id: PMID:26040712
supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly
- reference_id: PMID:26040713
supporting_text: GFP-CHMP4B transiently localises to telophase nuclei
- term:
id: GO:0032585
label: multivesicular body membrane
evidence_type: IDA
original_reference_id: PMID:16554368
qualifier: located_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: multivesicular body membrane.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0036258
label: multivesicular body assembly
evidence_type: NAS
original_reference_id: PMID:16505166
qualifier: involved_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0039702
label: viral budding via host ESCRT complex
evidence_type: IDA
original_reference_id: PMID:24878737
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B viral budding context: viral budding via host ESCRT complex.'
action: KEEP_AS_NON_CORE
reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release
- reference_id: PMID:22422861
supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process
- reference_id: PMID:24878737
supporting_text: ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission
- term:
id: GO:0043162
label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
evidence_type: IDA
original_reference_id: PMID:17984323
qualifier: involved_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0046761
label: viral budding from plasma membrane
evidence_type: IDA
original_reference_id: PMID:24878737
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B viral budding context: viral budding from plasma membrane.'
action: KEEP_AS_NON_CORE
reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release
- reference_id: PMID:22422861
supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process
- reference_id: PMID:24878737
supporting_text: ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission
- term:
id: GO:0051469
label: vesicle fusion with vacuole
evidence_type: NAS
original_reference_id: PMID:16505166
qualifier: involved_in
review:
summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: vesicle fusion with vacuole.'
action: MODIFY
reason: The evidence supports ESCRT/MVB delivery toward lysosomes rather than CHMP4B acting as a vacuole-fusion SNARE.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
proposed_replacement_terms:
- id: GO:1902774
label: late endosome to lysosome transport
- term:
id: GO:0061763
label: multivesicular body-lysosome fusion
evidence_type: NAS
original_reference_id: PMID:16505166
qualifier: involved_in
review:
summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: multivesicular body-lysosome fusion.'
action: MODIFY
reason: The evidence supports late endosome-to-lysosome/endolysosomal transport rather than CHMP4B as a direct MVB-lysosome fusion factor.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
proposed_replacement_terms:
- id: GO:1902774
label: late endosome to lysosome transport
- term:
id: GO:0061952
label: midbody abscission
evidence_type: IMP
original_reference_id: PMID:20616062
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B cytokinesis/abscission context: midbody abscission.'
action: KEEP_AS_NON_CORE
reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here.
supported_by:
- reference_id: PMID:22422861
supporting_text: CHMP4B was again the sole paralog required
- reference_id: PMID:22422861
supporting_text: GFP-CHMP4B localized transiently to the midbody arms immediately
- reference_id: PMID:21310966
supporting_text: ESCRT-III co-localized with constriction zones and was required for assembly of 17-nanometer-diameter filaments
- reference_id: UniProt:Q9H444
supporting_text: functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis
- term:
id: GO:0071985
label: multivesicular body sorting pathway
evidence_type: IDA
original_reference_id: PMID:16554368
qualifier: involved_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0090148
label: membrane fission
evidence_type: NAS
original_reference_id: PMID:19234443
qualifier: involved_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: membrane fission.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0097352
label: autophagosome maturation
evidence_type: IMP
original_reference_id: PMID:17984323
qualifier: involved_in
review:
summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: autophagosome maturation.'
action: ACCEPT
reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
supported_by:
- reference_id: PMID:21975012
supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation
- reference_id: PMID:21975012
supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A
- reference_id: PMID:17984323
supporting_text: Functional multivesicular bodies are required for autophagic clearance
- reference_id: PMID:17984323
supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:1901673
label: regulation of mitotic spindle assembly
evidence_type: IMP
original_reference_id: PMID:20616062
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: regulation of mitotic spindle assembly.'
action: KEEP_AS_NON_CORE
reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
supported_by:
- reference_id: PMID:20616062
supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers
- reference_id: PMID:20616062
supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- term:
id: GO:1902774
label: late endosome to lysosome transport
evidence_type: IMP
original_reference_id: PMID:17984323
qualifier: involved_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: late endosome to lysosome transport.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:1904930
label: amphisome membrane
evidence_type: IDA
original_reference_id: PMID:17984323
qualifier: located_in
review:
summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: amphisome membrane.'
action: ACCEPT
reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
supported_by:
- reference_id: PMID:21975012
supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation
- reference_id: PMID:21975012
supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A
- reference_id: PMID:17984323
supporting_text: Functional multivesicular bodies are required for autophagic clearance
- reference_id: PMID:17984323
supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0030496
label: midbody
evidence_type: EXP
original_reference_id: PMID:22422861
qualifier: located_in
review:
summary: 'Supported non-core CHMP4B cytokinesis/abscission context: midbody.'
action: KEEP_AS_NON_CORE
reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here.
supported_by:
- reference_id: PMID:22422861
supporting_text: CHMP4B was again the sole paralog required
- reference_id: PMID:22422861
supporting_text: GFP-CHMP4B localized transiently to the midbody arms immediately
- reference_id: PMID:21310966
supporting_text: ESCRT-III co-localized with constriction zones and was required for assembly of 17-nanometer-diameter filaments
- reference_id: UniProt:Q9H444
supporting_text: functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis
- term:
id: GO:0031902
label: late endosome membrane
evidence_type: EXP
original_reference_id: PMID:15511219
qualifier: located_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: late endosome membrane.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:33349255
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0050877
label: nervous system process
evidence_type: IMP
original_reference_id: PMID:21975012
qualifier: involved_in
review:
summary: Supported but broad non-core CHMP4B neuronal context.
action: KEEP_AS_NON_CORE
reason: hSnf7-2/CHMP4B is required for human neuronal survival and cargo turnover, but nervous system process is broad compared with the underlying ESCRT/MVB cargo-sorting mechanism.
supported_by:
- reference_id: PMID:21975012
supporting_text: hSnf7-1 and hSnf7-2 are required for the survival of human neurons
- reference_id: PMID:21975012
supporting_text: hSnf7-1- or hSnf7-2-contaning ESCRT-III regulates the trafficking of different transmembrane cargos
- term:
id: GO:0071985
label: multivesicular body sorting pathway
evidence_type: IMP
original_reference_id: PMID:21975012
qualifier: involved_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:34818527
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22162750
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0046761
label: viral budding from plasma membrane
evidence_type: IMP
original_reference_id: PMID:14505570
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B viral budding context: viral budding from plasma membrane.'
action: KEEP_AS_NON_CORE
reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release
- reference_id: PMID:22422861
supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process
- reference_id: PMID:24878737
supporting_text: ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission
- term:
id: GO:0000815
label: ESCRT III complex
evidence_type: IDA
original_reference_id: PMID:18209100
qualifier: part_of
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:18209100
qualifier: enables
review:
summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: identical protein binding.'
action: MODIFY
reason: Identical protein binding is less informative than CHMP4B/Snf7-family polymerization and membrane bending.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
proposed_replacement_terms:
- id: GO:0051258
label: protein polymerization
- id: GO:0180020
label: membrane bending activity
- term:
id: GO:0051258
label: protein polymerization
evidence_type: IDA
original_reference_id: PMID:18209100
qualifier: involved_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: protein polymerization.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0045296
label: cadherin binding
evidence_type: HDA
original_reference_id: PMID:25468996
qualifier: enables
review:
summary: 'Broad high-throughput/proximity annotation is not a core CHMP4B function: cadherin binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The E-cadherin proteomics evidence is broad proximity/localization evidence and does not establish cadherin binding or generic vesicle localization as an informative CHMP4B function.
supported_by:
- reference_id: PMID:25468996
supporting_text: proximity biotinylation and quantitative proteomics to identify 561 proteins in the vicinity
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: The E-cadherin proximity proteomics evidence is broad high-throughput context, not a core CHMP4B molecular function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:18641129
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0016236
label: macroautophagy
evidence_type: TAS
original_reference_id: PMID:20588296
qualifier: involved_in
review:
summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: macroautophagy.'
action: ACCEPT
reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
supported_by:
- reference_id: PMID:21975012
supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation
- reference_id: PMID:21975012
supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A
- reference_id: PMID:17984323
supporting_text: Functional multivesicular bodies are required for autophagic clearance
- reference_id: PMID:17984323
supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0031982
label: vesicle
evidence_type: IDA
original_reference_id: PMID:25468996
qualifier: located_in
review:
summary: 'Broad high-throughput/proximity annotation is not a core CHMP4B function: vesicle.'
action: MARK_AS_OVER_ANNOTATED
reason: The E-cadherin proteomics evidence is broad proximity/localization evidence and does not establish cadherin binding or generic vesicle localization as an informative CHMP4B function.
supported_by:
- reference_id: PMID:25468996
supporting_text: proximity biotinylation and quantitative proteomics to identify 561 proteins in the vicinity
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: The E-cadherin proximity proteomics evidence is broad high-throughput context, not a core CHMP4B molecular function.
- term:
id: GO:0000281
label: mitotic cytokinesis
evidence_type: IMP
original_reference_id: PMID:21310966
qualifier: involved_in
review:
summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: mitotic cytokinesis.'
action: MODIFY
reason: CHMP4B is specifically implicated in ESCRT-dependent midbody abscission rather than all of mitotic cytokinesis.
supported_by:
- reference_id: PMID:22422861
supporting_text: CHMP4B was again the sole paralog required
- reference_id: PMID:22422861
supporting_text: GFP-CHMP4B localized transiently to the midbody arms immediately
- reference_id: PMID:21310966
supporting_text: ESCRT-III co-localized with constriction zones and was required for assembly of 17-nanometer-diameter filaments
- reference_id: UniProt:Q9H444
supporting_text: functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis
proposed_replacement_terms:
- id: GO:0061952
label: midbody abscission
- term:
id: GO:0000815
label: ESCRT III complex
evidence_type: IDA
original_reference_id: PMID:21310966
qualifier: part_of
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0000815
label: ESCRT III complex
evidence_type: IDA
original_reference_id: PMID:26040712
qualifier: part_of
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0005635
label: nuclear envelope
evidence_type: IDA
original_reference_id: PMID:26040712
qualifier: located_in
review:
summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear envelope.'
action: KEEP_AS_NON_CORE
reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- reference_id: PMID:26040712
supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly
- reference_id: PMID:26040713
supporting_text: GFP-CHMP4B transiently localises to telophase nuclei
- term:
id: GO:0010458
label: exit from mitosis
evidence_type: IMP
original_reference_id: PMID:26040712
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: exit from mitosis.'
action: KEEP_AS_NON_CORE
reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- reference_id: PMID:26040712
supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly
- reference_id: PMID:26040713
supporting_text: GFP-CHMP4B transiently localises to telophase nuclei
- term:
id: GO:0030496
label: midbody
evidence_type: IDA
original_reference_id: PMID:21310966
qualifier: located_in
review:
summary: 'Supported non-core CHMP4B cytokinesis/abscission context: midbody.'
action: KEEP_AS_NON_CORE
reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here.
supported_by:
- reference_id: PMID:22422861
supporting_text: CHMP4B was again the sole paralog required
- reference_id: PMID:22422861
supporting_text: GFP-CHMP4B localized transiently to the midbody arms immediately
- reference_id: PMID:21310966
supporting_text: ESCRT-III co-localized with constriction zones and was required for assembly of 17-nanometer-diameter filaments
- reference_id: UniProt:Q9H444
supporting_text: functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis
- term:
id: GO:0031468
label: nuclear membrane reassembly
evidence_type: IMP
original_reference_id: PMID:26040712
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B nuclear-envelope/mitotic-exit context: nuclear membrane reassembly.'
action: KEEP_AS_NON_CORE
reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context but is secondary to CHMP4B core ESCRT-III MVB/endosomal membrane remodeling.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- reference_id: PMID:26040712
supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly
- reference_id: PMID:26040713
supporting_text: GFP-CHMP4B transiently localises to telophase nuclei
- term:
id: GO:0090148
label: membrane fission
evidence_type: IMP
original_reference_id: PMID:21310966
qualifier: involved_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: membrane fission.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0006914
label: autophagy
evidence_type: IMP
original_reference_id: PMID:24095276
qualifier: involved_in
review:
summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: autophagy.'
action: ACCEPT
reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
supported_by:
- reference_id: PMID:21975012
supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation
- reference_id: PMID:21975012
supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A
- reference_id: PMID:17984323
supporting_text: Functional multivesicular bodies are required for autophagic clearance
- reference_id: PMID:17984323
supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0000815
label: ESCRT III complex
evidence_type: TAS
original_reference_id: PMID:20588296
qualifier: part_of
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0036258
label: multivesicular body assembly
evidence_type: TAS
original_reference_id: PMID:20588296
qualifier: involved_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0039702
label: viral budding via host ESCRT complex
evidence_type: TAS
original_reference_id: PMID:20588296
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B viral budding context: viral budding via host ESCRT complex.'
action: KEEP_AS_NON_CORE
reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release
- reference_id: PMID:22422861
supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process
- reference_id: PMID:24878737
supporting_text: ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission
- term:
id: GO:0006914
label: autophagy
evidence_type: TAS
original_reference_id: PMID:21118109
qualifier: involved_in
review:
summary: 'Supported PN-relevant CHMP4B autophagy/endolysosomal annotation: autophagy.'
action: ACCEPT
reason: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation, and ESCRT/MVB function is required for autophagic clearance; these annotations are retained as PN-relevant endolysosomal/autophagy context.
supported_by:
- reference_id: PMID:21975012
supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation
- reference_id: PMID:21975012
supporting_text: hSnf7-2 and CHMP2B were more abundant than those containing CHMP2A
- reference_id: PMID:17984323
supporting_text: Functional multivesicular bodies are required for autophagic clearance
- reference_id: PMID:17984323
supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0000815
label: ESCRT III complex
evidence_type: IDA
original_reference_id: PMID:24878737
qualifier: part_of
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0030117
label: membrane coat
evidence_type: IDA
original_reference_id: PMID:24878737
qualifier: part_of
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: membrane coat.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: PMID:17701905
qualifier: located_in
review:
summary: 'True or plausible broad CHMP4B location: cytoplasm.'
action: KEEP_AS_NON_CORE
reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Cytoplasm. Cytosol. Late endosome membrane
- reference_id: UniProt:Q9H444
supporting_text: Membrane-associated
- term:
id: GO:0005768
label: endosome
evidence_type: IDA
original_reference_id: PMID:17701905
qualifier: located_in
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: endosome.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0036438
label: maintenance of lens transparency
evidence_type: IMP
original_reference_id: PMID:17701905
qualifier: involved_in
review:
summary: Supported non-core CHMP4B lens-transparency disease/physiology context.
action: KEEP_AS_NON_CORE
reason: CHMP4B variants cause dominant cataracts and support a lens-transparency phenotype, but this phenotype does not redefine the core ESCRT-III molecular function.
supported_by:
- reference_id: PMID:17701905
supporting_text: plays a vital role in the maintenance of lens transparency
- reference_id: PMID:17701905
supporting_text: key component of the endosome sorting complex required
- term:
id: GO:0046755
label: viral budding
evidence_type: IMP
original_reference_id: PMID:17701905
qualifier: involved_in
review:
summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: viral budding.'
action: MODIFY
reason: The viral-budding evidence is specifically host ESCRT-mediated budding, not generic viral budding.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release
- reference_id: PMID:22422861
supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process
- reference_id: PMID:24878737
supporting_text: ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission
proposed_replacement_terms:
- id: GO:0039702
label: viral budding via host ESCRT complex
- term:
id: GO:0010824
label: regulation of centrosome duplication
evidence_type: IMP
original_reference_id: PMID:20616062
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B centrosome/spindle/cell-cycle context: regulation of centrosome duplication.'
action: KEEP_AS_NON_CORE
reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance and chromosome segregation, but these cell-cycle annotations are secondary to CHMP4B core ESCRT-III membrane-remodeling function.
supported_by:
- reference_id: PMID:20616062
supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers
- reference_id: PMID:20616062
supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
- reference_id: UniProt:Q9H444
supporting_text: promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase
- term:
id: GO:0090611
label: obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway
evidence_type: IMP
original_reference_id: PMID:22547407
qualifier: involved_in
review:
summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway.'
action: MODIFY
reason: This obsolete ubiquitin-independent catabolic process term should be replaced by the non-obsolete MVB sorting pathway term.
supported_by:
- reference_id: PMID:22547407
supporting_text: PAR1 sorted to ILVs of MVBs through an ESCRT-III-dependent pathway independent of ubiquitination
- reference_id: PMID:22547407
supporting_text: ALIX binds to a YPX3L motif of PAR1 and recruits ESCRT-III to mediate MVB/lysosomal sorting
proposed_replacement_terms:
- id: GO:0071985
label: multivesicular body sorting pathway
- term:
id: GO:0039702
label: viral budding via host ESCRT complex
evidence_type: IGI
original_reference_id: PMID:24107264
qualifier: involved_in
review:
summary: 'Supported non-core CHMP4B viral budding context: viral budding via host ESCRT complex.'
action: KEEP_AS_NON_CORE
reason: CHMP4B is specifically required for ESCRT-dependent HIV/viral budding, but viral budding is a pathogen-hijacked ESCRT output rather than a core host proteostasis function.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release
- reference_id: PMID:22422861
supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process
- reference_id: PMID:24878737
supporting_text: ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission
- term:
id: GO:0070062
label: extracellular exosome
evidence_type: HDA
original_reference_id: PMID:23533145
qualifier: located_in
review:
summary: Plausible but broad non-core CHMP4B extracellular-exosome context.
action: KEEP_AS_NON_CORE
reason: CHMP4B/ESCRT biology supports exosome release, but high-throughput extracellular exosome localization is broad and secondary to the core ESCRT-III MVB membrane-remodeling function.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan
- reference_id: PMID:18209100
supporting_text: MVBs also fuse with the plasma membrane to secrete their ILVs as entities called exosomes
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:14519844
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0042803
label: protein homodimerization activity
evidence_type: IPI
original_reference_id: PMID:14519844
qualifier: enables
review:
summary: 'CHMP4B annotation should be replaced with a more accurate ESCRT-III term: protein homodimerization activity.'
action: MODIFY
reason: Homodimerization is less informative than CHMP4B/Snf7-family polymerization and membrane bending.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
proposed_replacement_terms:
- id: GO:0051258
label: protein polymerization
- id: GO:0180020
label: membrane bending activity
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:14505570
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0000815
label: ESCRT III complex
evidence_type: IDA
original_reference_id: PMID:21975012
qualifier: part_of
review:
summary: 'Supported core CHMP4B ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.'
action: ACCEPT
reason: CHMP4B is a Snf7-family ESCRT-III core subunit whose polymerization on endosomal/MVB membranes supports cargo sorting, membrane bending, and reverse-topology membrane fission.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:21975012
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005634
label: nucleus
evidence_type: IDA
original_reference_id: PMID:21975012
qualifier: located_in
review:
summary: 'True or plausible broad CHMP4B location: nucleus.'
action: KEEP_AS_NON_CORE
reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Cytoplasm. Cytosol. Late endosome membrane
- reference_id: UniProt:Q9H444
supporting_text: Membrane-associated
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: PMID:21975012
qualifier: located_in
review:
summary: 'True or plausible broad CHMP4B location: cytoplasm.'
action: KEEP_AS_NON_CORE
reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Cytoplasm. Cytosol. Late endosome membrane
- reference_id: UniProt:Q9H444
supporting_text: Membrane-associated
- term:
id: GO:0006620
label: post-translational protein targeting to endoplasmic reticulum membrane
evidence_type: IMP
original_reference_id: PMID:21975012
qualifier: involved_in
review:
summary: 'Unsupported CHMP4B annotation: post-translational protein targeting to ER membrane.'
action: REMOVE
reason: PMID:21975012 supports hSnf7-2/CHMP4B in neuronal endosomal cargo turnover and autophagosome accumulation, but does not support a role in post-translational targeting to the ER membrane.
supported_by:
- reference_id: PMID:21975012
supporting_text: hSnf7-2-containing ESCRT-III differentially regulates the turnover of distinct transmembrane cargos in human neurons
- reference_id: PMID:21975012
supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: PMID:21975012 supports neuronal cargo turnover and autophagosome accumulation, not post-translational targeting to the ER membrane.
- term:
id: GO:0009898
label: cytoplasmic side of plasma membrane
evidence_type: IDA
original_reference_id: PMID:18209100
qualifier: located_in
review:
summary: 'True or plausible broad CHMP4B location: cytoplasmic side of plasma membrane.'
action: KEEP_AS_NON_CORE
reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Cytoplasm. Cytosol. Late endosome membrane
- reference_id: UniProt:Q9H444
supporting_text: Membrane-associated
- term:
id: GO:0070062
label: extracellular exosome
evidence_type: HDA
original_reference_id: PMID:19056867
qualifier: located_in
review:
summary: Plausible but broad non-core CHMP4B extracellular-exosome context.
action: KEEP_AS_NON_CORE
reason: CHMP4B/ESCRT biology supports exosome release, but high-throughput extracellular exosome localization is broad and secondary to the core ESCRT-III MVB membrane-remodeling function.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan
- reference_id: PMID:18209100
supporting_text: MVBs also fuse with the plasma membrane to secrete their ILVs as entities called exosomes
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:12860994
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0070062
label: extracellular exosome
evidence_type: HDA
original_reference_id: PMID:20458337
qualifier: located_in
review:
summary: Plausible but broad non-core CHMP4B extracellular-exosome context.
action: KEEP_AS_NON_CORE
reason: CHMP4B/ESCRT biology supports exosome release, but high-throughput extracellular exosome localization is broad and secondary to the core ESCRT-III MVB membrane-remodeling function.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan
- reference_id: PMID:18209100
supporting_text: MVBs also fuse with the plasma membrane to secrete their ILVs as entities called exosomes
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:21543490
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-3159232
qualifier: located_in
review:
summary: 'True or plausible broad CHMP4B location: cytosol.'
action: KEEP_AS_NON_CORE
reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Cytoplasm. Cytosol. Late endosome membrane
- reference_id: UniProt:Q9H444
supporting_text: Membrane-associated
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-917693
qualifier: located_in
review:
summary: 'True or plausible broad CHMP4B location: cytosol.'
action: KEEP_AS_NON_CORE
reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Cytoplasm. Cytosol. Late endosome membrane
- reference_id: UniProt:Q9H444
supporting_text: Membrane-associated
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-917700
qualifier: located_in
review:
summary: 'True or plausible broad CHMP4B location: cytosol.'
action: KEEP_AS_NON_CORE
reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Cytoplasm. Cytosol. Late endosome membrane
- reference_id: UniProt:Q9H444
supporting_text: Membrane-associated
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9668389
qualifier: located_in
review:
summary: 'True or plausible broad CHMP4B location: cytosol.'
action: KEEP_AS_NON_CORE
reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Cytoplasm. Cytosol. Late endosome membrane
- reference_id: UniProt:Q9H444
supporting_text: Membrane-associated
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9668395
qualifier: located_in
review:
summary: 'True or plausible broad CHMP4B location: cytosol.'
action: KEEP_AS_NON_CORE
reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Cytoplasm. Cytosol. Late endosome membrane
- reference_id: UniProt:Q9H444
supporting_text: Membrane-associated
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9668398
qualifier: located_in
review:
summary: 'True or plausible broad CHMP4B location: cytosol.'
action: KEEP_AS_NON_CORE
reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Cytoplasm. Cytosol. Late endosome membrane
- reference_id: UniProt:Q9H444
supporting_text: Membrane-associated
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9668405
qualifier: located_in
review:
summary: 'True or plausible broad CHMP4B location: cytosol.'
action: KEEP_AS_NON_CORE
reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Cytoplasm. Cytosol. Late endosome membrane
- reference_id: UniProt:Q9H444
supporting_text: Membrane-associated
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9668415
qualifier: located_in
review:
summary: 'True or plausible broad CHMP4B location: cytosol.'
action: KEEP_AS_NON_CORE
reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Cytoplasm. Cytosol. Late endosome membrane
- reference_id: UniProt:Q9H444
supporting_text: Membrane-associated
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9668419
qualifier: located_in
review:
summary: 'True or plausible broad CHMP4B location: cytosol.'
action: KEEP_AS_NON_CORE
reason: This location is compatible with CHMP4B cycling between cytosol and recruited membrane-associated ESCRT-III assemblies, but it is too broad to represent the core function by itself.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Cytoplasm. Cytosol. Late endosome membrane
- reference_id: UniProt:Q9H444
supporting_text: Membrane-associated
- term:
id: GO:0030496
label: midbody
evidence_type: IDA
original_reference_id: PMID:22724069
qualifier: located_in
review:
summary: 'Supported non-core CHMP4B cytokinesis/abscission context: midbody.'
action: KEEP_AS_NON_CORE
reason: CHMP4B has strong evidence in ESCRT-dependent cytokinetic abscission, but this is a secondary topologically related ESCRT output rather than the central endosomal/proteostasis function emphasized here.
supported_by:
- reference_id: PMID:22422861
supporting_text: CHMP4B was again the sole paralog required
- reference_id: PMID:22422861
supporting_text: GFP-CHMP4B localized transiently to the midbody arms immediately
- reference_id: PMID:21310966
supporting_text: ESCRT-III co-localized with constriction zones and was required for assembly of 17-nanometer-diameter filaments
- reference_id: UniProt:Q9H444
supporting_text: functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:20208530
qualifier: enables
review:
summary: 'Over-annotated CHMP4B molecular-function annotation: protein binding.'
action: MARK_AS_OVER_ANNOTATED
reason: The cited interaction may be real, but protein binding is not informative for CHMP4B; the supported molecular function is ESCRT-III polymerization and membrane bending/scission on endosomal and related membranes.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: file:human/CHMP4B/CHMP4B-notes.md
supporting_text: Generic protein binding rows were treated as over-annotated because they do not capture the ESCRT-III polymer/membrane-remodeling function.
- term:
id: GO:0180020
label: membrane bending activity
evidence_type: IDA
original_reference_id: PMID:18209100
qualifier: enables
review:
summary: New CHMP4B molecular-function annotation supported by direct hSnf7-2 filament/membrane curvature evidence.
action: NEW
reason: PMID:18209100 directly includes hSnf7-2/CHMP4B and shows that CHMP4-containing ESCRT-III filaments promote or stabilize negative membrane curvature and outward budding, making membrane bending activity more informative than generic binding terms.
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:18209100
supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO terms
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
findings: []
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning models
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:12860994
title: The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting.
findings:
- statement: CHMP4B/CHMP4b associates with ALIX and is implicated in MVB sorting and endosomal localization.
- id: PMID:14505570
title: The protein network of HIV budding.
findings: []
- id: PMID:14519844
title: Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins.
findings: []
- id: PMID:15511219
title: Human CHMP6, a myristoylated ESCRT-III protein, interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting.
findings:
- statement: CHMP6 interacts directly with CHMP4B/Shax and regulates endosomal cargo sorting.
- id: PMID:16189514
title: Towards a proteome-scale map of the human protein-protein interaction network.
findings: []
- id: PMID:16505166
title: Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1.
findings: []
- id: PMID:16554368
title: The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptor.
findings: []
- 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: []
- id: PMID:16856878
title: CHMP7, a novel ESCRT-III-related protein, associates with CHMP4b and functions in the endosomal sorting pathway.
findings: []
- id: PMID:17174262
title: HD-PTP and Alix share some membrane-traffic related proteins that interact with their Bro1 domains or proline-rich regions.
findings: []
- id: PMID:17500595
title: Huntingtin interacting proteins are genetic modifiers of neurodegeneration.
findings: []
- id: PMID:17701905
title: CHMP4B, a novel gene for autosomal dominant cataracts linked to chromosome 20q.
findings:
- statement: CHMP4B mutations cause autosomal dominant cataracts and support a lens-transparency phenotype.
- id: PMID:17711858
title: The MIT domain of UBPY constitutes a CHMP binding and endosomal localization signal required for efficient epidermal growth factor receptor degradation.
findings: []
- id: PMID:17984323
title: Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease.
findings: []
- id: PMID:18209100
title: Plasma membrane deformation by circular arrays of ESCRT-III protein filaments.
findings:
- statement: Direct hSnf7-2/CHMP4B evidence supports ESCRT-III filament polymerization, membrane bending, and negative-curvature budding.
- id: PMID:18434552
title: The Bro1-related protein HD-PTP/PTPN23 is required for endosomal cargo sorting and multivesicular body morphogenesis.
findings: []
- id: PMID:18511562
title: ALIX-CHMP4 interactions in the human ESCRT pathway.
findings: []
- id: PMID:18641129
title: Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release.
findings: []
- id: PMID:19056867
title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
findings: []
- id: PMID:19234443
title: Membrane scission by the ESCRT-III complex.
findings: []
- id: PMID:19523902
title: A crescent-shaped ALIX dimer targets ESCRT-III CHMP4 filaments.
findings: []
- id: PMID:20208530
title: PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody.
findings: []
- id: PMID:20458337
title: MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
findings: []
- id: PMID:20588296
title: 'Membrane budding and scission by the ESCRT machinery: it''s all in the neck.'
findings: []
- id: PMID:20616062
title: Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance.
findings: []
- id: PMID:21118109
title: The role of ESCRT proteins in fusion events involving lysosomes, endosomes and autophagosomes.
findings: []
- id: PMID:21310966
title: Cortical constriction during abscission involves helices of ESCRT-III-dependent filaments.
findings:
- statement: ESCRT-III-dependent filaments localize to constriction zones and support cortical constriction during abscission.
- id: PMID:21543490
title: Mechanism of inhibition of retrovirus release from cells by interferon-induced gene ISG15.
findings: []
- id: PMID:21889351
title: The Phe105 loop of Alix Bro1 domain plays a key role in HIV-1 release.
findings: []
- id: PMID:21975012
title: ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate transmembrane cargos in hESC-derived human neurons.
findings:
- statement: Human-neuron hSnf7-2/CHMP4B knockdown causes autophagosome accumulation and altered transmembrane cargo turnover.
- id: PMID:22162750
title: Structure of the Bro1 domain protein BROX and functional analyses of the ALIX Bro1 domain in HIV-1 budding.
findings: []
- id: PMID:22422861
title: ESCRT-III governs the Aurora B-mediated abscission checkpoint through CHMP4C.
findings:
- statement: CHMP4B is the CHMP4 paralog required for MHC-I degradation, HIV release, and completion of cytokinesis in this study.
- id: PMID:22484091
title: Two distinct binding modes define the interaction of Brox with the C-terminal tails of CHMP5 and CHMP4B.
findings: []
- id: PMID:22547407
title: ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting.
findings:
- statement: ALIX-CHMP4/ESCRT-III mediates ubiquitin-independent PAR1 sorting to MVB/lysosomal degradation.
- id: PMID:22724069
title: The chromosomal passenger complex controls the function of endosomal sorting complex required for transport-III Snf7 proteins during cytokinesis.
findings: []
- id: PMID:23051622
title: ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding.
findings: []
- id: PMID:23533145
title: In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
findings: []
- id: PMID:24095276
title: Syntaxin 13, a genetic modifier of mutant CHMP2B in frontotemporal dementia, is required for autophagosome maturation.
findings: []
- id: PMID:24107264
title: ESCRT requirements for EIAV budding.
findings: []
- id: PMID:24482116
title: ESCRT machinery is required for plasma membrane repair.
findings: []
- id: PMID:24878737
title: Structure of cellular ESCRT-III spirals and their relationship to HIV budding.
findings: []
- id: PMID:25468996
title: E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
findings:
- statement: E-cadherin BioID/proteomics provides broad proximity evidence that should not be treated as core CHMP4B molecular function.
- id: PMID:26040712
title: Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing.
findings: []
- id: PMID:26040713
title: ESCRT-III controls nuclear envelope reformation.
findings: []
- id: PMID:26496610
title: A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
findings: []
- id: PMID:32296183
title: A reference map of the human binary protein interactome.
findings: []
- id: PMID:32814053
title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
findings: []
- id: PMID:33349255
title: Lethal (2) giant discs (Lgd)/CC2D1 is required for the full activity of the ESCRT machinery.
findings: []
- id: PMID:34818527
title: The ESCRT machinery counteracts Nesprin-2G-mediated mechanical forces during nuclear envelope repair.
findings: []
- id: PMID:35271311
title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
findings: []
- id: PMID:36107470
title: Comprehensive analysis of the human ESCRT-III-MIT domain interactome reveals new cofactors for cytokinetic abscission.
findings: []
- id: Reactome:R-HSA-3159232
title: Recruitment Of HIV Virion Budding Machinery
findings: []
- id: Reactome:R-HSA-917693
title: ESCRT Disassembly
findings: []
- id: Reactome:R-HSA-917700
title: MVB Vesicle Formation
findings: []
- id: Reactome:R-HSA-9668389
title: VPS4 binds ESCRT-III assemblies at nuclear envelope (NE) fenestrations
findings: []
- id: Reactome:R-HSA-9668395
title: CHMP7 binds CC2D1B
findings: []
- id: Reactome:R-HSA-9668398
title: CHMP7 binds CHMP4B, which recruits other subunits of the ESCRT-III complex
findings: []
- id: Reactome:R-HSA-9668405
title: SPAST (spastin) binds the IST1 subunit of ESCRT-III at the sites of microtubule attachment to chromatin
findings: []
- id: Reactome:R-HSA-9668415
title: VPS4 mediates disassembly of ESCRTIII subunits to promote sealing of holes in the nuclear envelope
findings: []
- id: Reactome:R-HSA-9668419
title: SPAST (spastin) mediates the severing of microtubules at chromosome attachment sites
findings: []
- id: file:human/CHMP4B/CHMP4B-notes.md
title: Local curation notes for CHMP4B
findings:
- statement: Local synthesis identifies CHMP4B/Snf7-2 ESCRT-III polymerization, membrane bending, and MVB/endolysosomal sorting as core functions, with autophagy and other ESCRT outputs retained in context.
- id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
title: Falcon deep research report for CHMP4B
findings:
- statement: Falcon synthesis agrees with cached primary evidence that CHMP4B is a non-enzymatic ESCRT-III membrane-remodeling scaffold involved in reverse-topology constriction and scission.
core_functions:
- molecular_function:
id: GO:0180020
label: membrane bending activity
description: CHMP4B/Snf7-2 is a core ESCRT-III structural subunit that polymerizes into curved membrane-associated filaments and promotes or stabilizes negative membrane curvature for reverse-topology budding/fission.
in_complex:
id: GO:0000815
label: ESCRT III complex
directly_involved_in:
- id: GO:0090148
label: membrane fission
locations:
- id: GO:0031902
label: late endosome membrane
- id: GO:0032585
label: multivesicular body membrane
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
- reference_id: PMID:18209100
supporting_text: hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- reference_id: PMID:18209100
supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
- reference_id: PMID:19234443
supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- description: CHMP4B-containing ESCRT-III assemblies mediate MVB intraluminal vesicle formation and endosomal cargo sorting toward lysosomal degradation, including ubiquitin-dependent cargo and ALIX/CHMP4-dependent ubiquitin-independent cargo routes.
in_complex:
id: GO:0000815
label: ESCRT III complex
directly_involved_in:
- id: GO:0071985
label: multivesicular body sorting pathway
- id: GO:0036258
label: multivesicular body assembly
- id: GO:0043162
label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
locations:
- id: GO:0032585
label: multivesicular body membrane
- id: GO:0005768
label: endosome
supported_by:
- reference_id: UniProt:Q9H444
supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
- reference_id: UniProt:Q9H444
supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- reference_id: PMID:12860994
supporting_text: CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting
- reference_id: PMID:15511219
supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting
- reference_id: PMID:22547407
supporting_text: PAR1 sorted to ILVs of MVBs through an ESCRT-III-dependent pathway independent of ubiquitination
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
- description: CHMP4B/Snf7-2 contributes to proteostasis through ESCRT-dependent endolysosomal cargo turnover and autophagy/autophagosome maturation contexts; direct human-neuron knockdown causes autophagosome accumulation and altered transmembrane cargo turnover.
in_complex:
id: GO:0000815
label: ESCRT III complex
directly_involved_in:
- id: GO:0097352
label: autophagosome maturation
- id: GO:0016236
label: macroautophagy
- id: GO:1902774
label: late endosome to lysosome transport
locations:
- id: GO:0000421
label: autophagosome membrane
- id: GO:1904930
label: amphisome membrane
- id: GO:0005765
label: lysosomal membrane
supported_by:
- reference_id: PMID:21975012
supporting_text: SiRNA knockdown of hSnf7-2 in human neurons leads to autophagosome accumulation
- reference_id: PMID:21975012
supporting_text: reduced expression of hSnf7-1 or hSnf7-2 led to accumulation of epidermal growth factor receptor
- reference_id: PMID:17984323
supporting_text: Functional multivesicular bodies are required for autophagic clearance
- reference_id: PMID:24095276
supporting_text: STX13 is a genetic modifier of ESCRT-III dysfunction and participates in the maturation of phagophores into closed autophagosomes
- reference_id: file:human/CHMP4B/CHMP4B-deep-research-falcon.md
supporting_text: polymerizes on membranes as part of **ESCRT-III** to drive **reverse-topology membrane constriction and scission**
proposed_new_terms: []
suggested_questions:
- question: Which CHMP4 paralog is the dominant Snf7-family subunit during human phagophore closure and autophagosome maturation in endogenous cells?
- question: Should GO annotations distinguish CHMP4B direct membrane-bending/polymer function from broader ESCRT output processes such as viral budding, plasma membrane repair, nuclear envelope sealing, and cytokinetic abscission?
- question: How do CHMP4B-CHMP2B-enriched ESCRT-III assemblies differ from CHMP4A-CHMP2A assemblies in neuronal endosomal cargo turnover and proteostasis?
suggested_experiments:
- description: Use endogenous CHMP4B tagging plus acute depletion/rescue during starvation-induced autophagy and selective cargo turnover assays to image recruitment to phagophores, autophagosomes, amphisomes, and endosomes.
hypothesis: If CHMP4B directly participates in autophagosome maturation or closure, it should be transiently recruited to autophagy membranes and rescue should require its polymerization/membrane-binding region.
- description: Compare wild-type CHMP4B with ALIX-binding, CHMP2B-interaction, and C-terminal autoinhibition mutants in MVB cargo sorting, HIV budding, cytokinetic abscission, and neuronal receptor turnover assays.
hypothesis: CHMP4B uses the same Snf7-family filament core across ESCRT outputs, but partner and recruitment requirements differ by membrane context.
- description: Biochemically reconstitute CHMP4B-containing human ESCRT-III polymers with CHMP2B, CHMP3, CHMP6, and VPS4 and test membrane bending/scission on defined liposomes.
hypothesis: CHMP4B contributes Snf7-family filament curvature that can drive membrane bending and support reverse-topology scission in a minimal human ESCRT-III module.
