VPS4B

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0016197 endosomal transport	IBA GO_REF:0000033	ACCEPT	Summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
GO:0016887 ATP hydrolysis activity	IBA GO_REF:0000033	ACCEPT	Summary: Core VPS4B function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4B and is directly supported by VPS4B biochemical and UniProt evidence. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	IBA GO_REF:0000033	ACCEPT	Summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
GO:0090611 obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway	IBA GO_REF:0000033	MODIFY	Summary: The annotation captures a real ubiquitin-independent MVB-sorting context, but the current GO term is obsolete. Reason: Use a current MVB sorting pathway term rather than retaining an obsolete ubiquitin-independent protein catabolic process term. Proposed replacements: multivesicular body sorting pathway Supporting Evidence: PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
GO:0000922 spindle pole	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
GO:0005524 ATP binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Reviewed as peripheral or insufficiently specific relative to the core VPS4B ESCRT ATPase role. Reason: No direct contradiction was found, but this annotation should not define VPS4B core function. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
GO:0005737 cytoplasm	IEA GO_REF:0000117	ACCEPT	Summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function. Reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1 PMID:16757520 SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
GO:0005813 centrosome	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
GO:0006997 nucleus organization	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4B molecular role. Reason: Keep as a non-core ESCRT membrane-sealing or nuclear-organization context; VPS4B acts through ESCRT-III remodeling rather than as a nucleus-organization factor per se. Supporting Evidence: PMID:28242692 In mammals, VPS4 depletion induces nuclear morphology defects
GO:0007041 lysosomal transport	IEA GO_REF:0000117	MODIFY	Summary: The broad lysosomal transport annotation reflects VPS4B late-endosomal/MVB trafficking function. Reason: A more specific late endosome-to-lysosome/MVB sorting pathway term better captures the supported role. Proposed replacements: late endosome to lysosome transport via multivesicular body sorting pathway Supporting Evidence: PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
GO:0007080 mitotic metaphase chromosome alignment	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: The cell-cycle/centriole annotation overstates downstream phenotypes from VPS4B/ESCRT depletion. Reason: Available evidence supports ESCRT-mediated abscission and centrosome/spindle phenotypes, not direct control of this specific cell-cycle regulatory process as a core function. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
GO:0010389 regulation of G2/M transition of mitotic cell cycle	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: The cell-cycle/centriole annotation overstates downstream phenotypes from VPS4B/ESCRT depletion. Reason: Available evidence supports ESCRT-mediated abscission and centrosome/spindle phenotypes, not direct control of this specific cell-cycle regulatory process as a core function. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
GO:0016887 ATP hydrolysis activity	IEA GO_REF:0000120	ACCEPT	Summary: Core VPS4B function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4B and is directly supported by VPS4B biochemical and UniProt evidence. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0031902 late endosome membrane	IEA GO_REF:0000044	ACCEPT	Summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function. Reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1 PMID:16757520 SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
GO:0039702 viral budding via host ESCRT complex	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Directly supported viral/plasma-membrane ESCRT context, but this is host-pathogen exploitation of VPS4B machinery rather than the core cellular function. Reason: Keep as a real non-core ESCRT output; do not use it to define the primary function of VPS4B. Supporting Evidence: PMID:14505570 The protein network of HIV budding. PMID:17940959 A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80%
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	IEA GO_REF:0000117	ACCEPT	Summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
GO:0051261 protein depolymerization	IEA GO_REF:0000117	MODIFY	Summary: VPS4B disassembles ESCRT-III assemblies rather than depolymerizing proteins generally. Reason: ESCRT III complex disassembly is the specific process supported by VPS4B biochemical evidence. Proposed replacements: ESCRT III complex disassembly Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
GO:0061952 midbody abscission	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
GO:0090543 Flemming body	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
GO:0090611 obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway	IEA GO_REF:0000117	MODIFY	Summary: The annotation captures a real ubiquitin-independent MVB-sorting context, but the current GO term is obsolete. Reason: Use a current MVB sorting pathway term rather than retaining an obsolete ubiquitin-independent protein catabolic process term. Proposed replacements: multivesicular body sorting pathway Supporting Evidence: PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
GO:1903543 positive regulation of exosomal secretion	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Supported positive exosome-release context for VPS4A/B but not the primary cellular function. Reason: Exosome secretion is one downstream ESCRT-dependent output of VPS4B activity, so retain as non-core. Supporting Evidence: UniProt:O75351 VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan
GO:0005515 protein binding	IPI PMID:17928862 ESCRT-III recognition by VPS4 ATPases.	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function. Reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported. Supporting Evidence: file:human/VPS4B/VPS4B-notes.md Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function. Reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported. Supporting Evidence: file:human/VPS4B/VPS4B-notes.md Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function. Reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported. Supporting Evidence: file:human/VPS4B/VPS4B-notes.md Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function. Reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported. Supporting Evidence: file:human/VPS4B/VPS4B-notes.md Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function. Reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported. Supporting Evidence: file:human/VPS4B/VPS4B-notes.md Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0005829 cytosol	IEA GO_REF:0000107	ACCEPT	Summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function. Reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1 PMID:16757520 SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
GO:0036258 multivesicular body assembly	IEA GO_REF:0000107	ACCEPT	Summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
GO:0046761 viral budding from plasma membrane	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Directly supported viral/plasma-membrane ESCRT context, but this is host-pathogen exploitation of VPS4B machinery rather than the core cellular function. Reason: Keep as a real non-core ESCRT output; do not use it to define the primary function of VPS4B. Supporting Evidence: PMID:14505570 The protein network of HIV budding. PMID:17940959 A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80%
GO:0061738 late endosomal microautophagy	IEA GO_REF:0000107	UNDECIDED	Summary: Late endosomal microautophagy is plausible for ESCRT machinery, but this specific human VPS4B row is automated/transferred in the local files. Reason: Retain uncertainty pending direct human evidence or a reviewed source tying VPS4B specifically to late endosomal microautophagy. Supporting Evidence: PMID:17428789 deletion of VPS4 and VPS36 caused impaired maturation of the vacuolar proaminopeptidase I (pAPI) via autophagy or the cytosol to vacuole targeting pathway PMID:20588296 ESCRT-III-mediated membrane neck cleavage is crucial for many processes, including the biogenesis of multivesicular bodies, viral budding, cytokinesis, and probably autophagy.
GO:0001778 plasma membrane repair	NAS PMID:24482116 ESCRT machinery is required for plasma membrane repair.	KEEP AS NON CORE	Summary: Supported plasma membrane repair context for ESCRT machinery, retained as a non-core VPS4B output. Reason: Plasma membrane repair uses ESCRT-mediated shedding/fission but is a specialized context of the core ESCRT remodeling machinery. Supporting Evidence: 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 of wounded portions.
GO:0005643 nuclear pore	NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...	KEEP AS NON CORE	Summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4B molecular role. Reason: Keep as a non-core ESCRT membrane-sealing or nuclear-organization context; VPS4B acts through ESCRT-III remodeling rather than as a nucleus-organization factor per se. Supporting Evidence: PMID:28242692 In mammals, VPS4 depletion induces nuclear morphology defects
GO:0005886 plasma membrane	NAS PMID:19234443 Membrane scission by the ESCRT-III complex.	KEEP AS NON CORE	Summary: Directly supported viral/plasma-membrane ESCRT context, but this is host-pathogen exploitation of VPS4B machinery rather than the core cellular function. Reason: Keep as a real non-core ESCRT output; do not use it to define the primary function of VPS4B. Supporting Evidence: PMID:14505570 The protein network of HIV budding. PMID:17940959 A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80%
GO:0006914 autophagy	NAS PMID:17428789 Phosphatidylethanolamine, a limiting factor of autophagy in ...	MARK AS OVER ANNOTATED	Summary: Autophagy connection is plausible for ESCRT machinery, but the local cached evidence for this specific VPS4B annotation is yeast-only or review-level rather than direct human VPS4B evidence. Reason: The annotation overstates direct evidence for human VPS4B in macroautophagy/autophagosome maturation. The core supported role remains ESCRT-III disassembly and membrane remodeling. Supporting Evidence: PMID:17428789 deletion of VPS4 and VPS36 caused impaired maturation of the vacuolar proaminopeptidase I (pAPI) via autophagy or the cytosol to vacuole targeting pathway PMID:20588296 ESCRT-III-mediated membrane neck cleavage is crucial for many processes, including the biogenesis of multivesicular bodies, viral budding, cytokinesis, and probably autophagy.
GO:0006997 nucleus organization	NAS PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4B molecular role. Reason: Keep as a non-core ESCRT membrane-sealing or nuclear-organization context; VPS4B acts through ESCRT-III remodeling rather than as a nucleus-organization factor per se. Supporting Evidence: PMID:28242692 In mammals, VPS4 depletion induces nuclear morphology defects
GO:0030496 midbody	NAS PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly...	KEEP AS NON CORE	Summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
GO:0031468 nuclear membrane reassembly	NAS PMID:26040713 ESCRT-III controls nuclear envelope reformation.	KEEP AS NON CORE	Summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4B molecular role. Reason: Keep as a non-core ESCRT membrane-sealing or nuclear-organization context; VPS4B acts through ESCRT-III remodeling rather than as a nucleus-organization factor per se. Supporting Evidence: PMID:28242692 In mammals, VPS4 depletion induces nuclear morphology defects
GO:0036258 multivesicular body assembly	NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...	ACCEPT	Summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
GO:0046761 viral budding from plasma membrane	IMP PMID:16193069 Structural and mechanistic studies of VPS4 proteins.	KEEP AS NON CORE	Summary: Directly supported viral/plasma-membrane ESCRT context, but this is host-pathogen exploitation of VPS4B machinery rather than the core cellular function. Reason: Keep as a real non-core ESCRT output; do not use it to define the primary function of VPS4B. Supporting Evidence: PMID:14505570 The protein network of HIV budding. PMID:17940959 A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80%
GO:0061764 late endosome to lysosome transport via multivesicular body sorting pathway	NAS PMID:9211789 The VPS4 gene is involved in protein transport out of a yeas...	ACCEPT	Summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
GO:0061952 midbody abscission	NAS PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
GO:0071985 multivesicular body sorting pathway	NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...	ACCEPT	Summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
GO:0090148 membrane fission	NAS PMID:19234443 Membrane scission by the ESCRT-III complex.	ACCEPT	Summary: Supported as an ESCRT/VPS4 membrane-remodeling output, with direct VPS4B disassembly evidence and broader ESCRT membrane-fission support. Reason: VPS4B-controlled ESCRT-III polymer remodeling supports membrane-neck constriction/fission in MVB and related pathways. Supporting Evidence: PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
GO:0097352 autophagosome maturation	NAS PMID:9211789 The VPS4 gene is involved in protein transport out of a yeas...	MARK AS OVER ANNOTATED	Summary: Autophagy connection is plausible for ESCRT machinery, but the local cached evidence for this specific VPS4B annotation is yeast-only or review-level rather than direct human VPS4B evidence. Reason: The annotation overstates direct evidence for human VPS4B in macroautophagy/autophagosome maturation. The core supported role remains ESCRT-III disassembly and membrane remodeling. Supporting Evidence: PMID:17428789 deletion of VPS4 and VPS36 caused impaired maturation of the vacuolar proaminopeptidase I (pAPI) via autophagy or the cytosol to vacuole targeting pathway PMID:20588296 ESCRT-III-mediated membrane neck cleavage is crucial for many processes, including the biogenesis of multivesicular bodies, viral budding, cytokinesis, and probably autophagy.
GO:1904949 ATPase complex	NAS PMID:19278657 Three-dimensional structure of AAA ATPase Vps4: advancing st...	ACCEPT	Summary: Core VPS4B function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4B and is directly supported by VPS4B biochemical and UniProt evidence. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0031902 late endosome membrane	ISS GO_REF:0000024	ACCEPT	Summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function. Reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1 PMID:16757520 SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
GO:0046761 viral budding from plasma membrane	IMP PMID:14505570 The protein network of HIV budding.	KEEP AS NON CORE	Summary: Directly supported viral/plasma-membrane ESCRT context, but this is host-pathogen exploitation of VPS4B machinery rather than the core cellular function. Reason: Keep as a real non-core ESCRT output; do not use it to define the primary function of VPS4B. Supporting Evidence: PMID:14505570 The protein network of HIV budding. PMID:17940959 A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80%
GO:0046761 viral budding from plasma membrane	IMP PMID:17940959 Involvement of vacuolar protein sorting pathway in Ebola vir...	KEEP AS NON CORE	Summary: Directly supported viral/plasma-membrane ESCRT context, but this is host-pathogen exploitation of VPS4B machinery rather than the core cellular function. Reason: Keep as a real non-core ESCRT output; do not use it to define the primary function of VPS4B. Supporting Evidence: PMID:14505570 The protein network of HIV budding. PMID:17940959 A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80%
GO:0016887 ATP hydrolysis activity	IDA PMID:18687924 Helical structures of ESCRT-III are disassembled by VPS4.	ACCEPT	Summary: Core VPS4B function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4B and is directly supported by VPS4B biochemical and UniProt evidence. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0005515 protein binding	IPI PMID:18687924 Helical structures of ESCRT-III are disassembled by VPS4.	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function. Reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported. Supporting Evidence: file:human/VPS4B/VPS4B-notes.md Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0044877 protein-containing complex binding	IDA PMID:18687924 Helical structures of ESCRT-III are disassembled by VPS4.	ACCEPT	Summary: Core VPS4B function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4B and is directly supported by VPS4B biochemical and UniProt evidence. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:1904903 ESCRT III complex disassembly	IDA PMID:18687924 Helical structures of ESCRT-III are disassembled by VPS4.	ACCEPT	Summary: Core VPS4B function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4B and is directly supported by VPS4B biochemical and UniProt evidence. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0061952 midbody abscission	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
GO:0016236 macroautophagy	NAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	MARK AS OVER ANNOTATED	Summary: Autophagy connection is plausible for ESCRT machinery, but the local cached evidence for this specific VPS4B annotation is yeast-only or review-level rather than direct human VPS4B evidence. Reason: The annotation overstates direct evidence for human VPS4B in macroautophagy/autophagosome maturation. The core supported role remains ESCRT-III disassembly and membrane remodeling. Supporting Evidence: PMID:17428789 deletion of VPS4 and VPS36 caused impaired maturation of the vacuolar proaminopeptidase I (pAPI) via autophagy or the cytosol to vacuole targeting pathway PMID:20588296 ESCRT-III-mediated membrane neck cleavage is crucial for many processes, including the biogenesis of multivesicular bodies, viral budding, cytokinesis, and probably autophagy.
GO:0036258 multivesicular body assembly	NAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	ACCEPT	Summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
GO:1904903 ESCRT III complex disassembly	NAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	ACCEPT	Summary: Core VPS4B function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4B and is directly supported by VPS4B biochemical and UniProt evidence. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0005515 protein binding	IPI PMID:18385515 Novel interactions of ESCRT-III with LIP5 and VPS4 and their...	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function. Reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported. Supporting Evidence: file:human/VPS4B/VPS4B-notes.md Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0005515 protein binding	IPI PMID:23105106 Interactions of the human LIP5 regulatory protein with endos...	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function. Reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported. Supporting Evidence: file:human/VPS4B/VPS4B-notes.md Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0005515 protein binding	IPI PMID:16193069 Structural and mechanistic studies of VPS4 proteins.	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function. Reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported. Supporting Evidence: file:human/VPS4B/VPS4B-notes.md Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0042802 identical protein binding	IDA PMID:16193069 Structural and mechanistic studies of VPS4 proteins.	MARK AS OVER ANNOTATED	Summary: Identical protein binding is too generic and does not capture the VPS4B oligomeric ATPase mechanism. Reason: VPS4B oligomerization is better discussed as part of ATPase assembly and ESCRT-III disassembly, not as a standalone identical-protein-binding function. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
GO:0042803 protein homodimerization activity	IDA PMID:16193069 Structural and mechanistic studies of VPS4 proteins.	KEEP AS NON CORE	Summary: VPS4B oligomerization is a real mechanistic property of the ATPase but not an informative core molecular function by itself. Reason: Retain as non-core because VPS4B forms ATP-dependent oligomeric assemblies, while the core function is ATP-dependent ESCRT-III disassembly. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
GO:0051261 protein depolymerization	IDA PMID:18687924 Helical structures of ESCRT-III are disassembled by VPS4.	MODIFY	Summary: VPS4B disassembles ESCRT-III assemblies rather than depolymerizing proteins generally. Reason: ESCRT III complex disassembly is the specific process supported by VPS4B biochemical evidence. Proposed replacements: ESCRT III complex disassembly Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
GO:0000922 spindle pole	IDA PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
GO:0005634 nucleus	IDA PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4B molecular role. Reason: Keep as a non-core ESCRT membrane-sealing or nuclear-organization context; VPS4B acts through ESCRT-III remodeling rather than as a nucleus-organization factor per se. Supporting Evidence: PMID:28242692 In mammals, VPS4 depletion induces nuclear morphology defects
GO:0005737 cytoplasm	IDA PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	ACCEPT	Summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function. Reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1 PMID:16757520 SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
GO:0005813 centrosome	IDA PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
GO:0006997 nucleus organization	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4B molecular role. Reason: Keep as a non-core ESCRT membrane-sealing or nuclear-organization context; VPS4B acts through ESCRT-III remodeling rather than as a nucleus-organization factor per se. Supporting Evidence: PMID:28242692 In mammals, VPS4 depletion induces nuclear morphology defects
GO:0007080 mitotic metaphase chromosome alignment	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	MARK AS OVER ANNOTATED	Summary: The cell-cycle/centriole annotation overstates downstream phenotypes from VPS4B/ESCRT depletion. Reason: Available evidence supports ESCRT-mediated abscission and centrosome/spindle phenotypes, not direct control of this specific cell-cycle regulatory process as a core function. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
GO:0010824 regulation of centrosome duplication	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
GO:0010971 positive regulation of G2/M transition of mitotic cell cycle	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	MARK AS OVER ANNOTATED	Summary: The cell-cycle/centriole annotation overstates downstream phenotypes from VPS4B/ESCRT depletion. Reason: Available evidence supports ESCRT-mediated abscission and centrosome/spindle phenotypes, not direct control of this specific cell-cycle regulatory process as a core function. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
GO:0090543 Flemming body	IDA PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
GO:1901673 regulation of mitotic spindle assembly	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
GO:1903724 positive regulation of centriole elongation	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	MARK AS OVER ANNOTATED	Summary: The cell-cycle/centriole annotation overstates downstream phenotypes from VPS4B/ESCRT depletion. Reason: Available evidence supports ESCRT-mediated abscission and centrosome/spindle phenotypes, not direct control of this specific cell-cycle regulatory process as a core function. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
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: The annotation captures a real ubiquitin-independent MVB-sorting context, but the current GO term is obsolete. Reason: Use a current MVB sorting pathway term rather than retaining an obsolete ubiquitin-independent protein catabolic process term. Proposed replacements: multivesicular body sorting pathway Supporting Evidence: PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
GO:1903543 positive regulation of exosomal secretion	IMP PMID:22660413 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.	KEEP AS NON CORE	Summary: Supported positive exosome-release context for VPS4A/B but not the primary cellular function. Reason: Exosome secretion is one downstream ESCRT-dependent output of VPS4B activity, so retain as non-core. Supporting Evidence: UniProt:O75351 VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan
GO:1903542 negative regulation of exosomal secretion	IMP PMID:24105262 Analysis of ESCRT functions in exosome biogenesis, compositi...	KEEP AS NON CORE	Summary: Supported context-dependent negative regulation of EV secretion in a HeLa-CIITA RNAi screen. Reason: This exosome phenotype is cell/cargo-context dependent and non-core relative to ATP-dependent ESCRT-III disassembly. Supporting Evidence: PMID:24105262 depletion of VPS4B augmented this secretion while not altering the features of EVs.
GO:0043162 ubiquitin-dependent 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...	ACCEPT	Summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
GO:0039702 viral budding via host ESCRT complex	IGI PMID:24107264 ESCRT requirements for EIAV budding.	KEEP AS NON CORE	Summary: Directly supported viral/plasma-membrane ESCRT context, but this is host-pathogen exploitation of VPS4B machinery rather than the core cellular function. Reason: Keep as a real non-core ESCRT output; do not use it to define the primary function of VPS4B. Supporting Evidence: PMID:14505570 The protein network of HIV budding. PMID:17940959 A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80%
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	MARK AS OVER ANNOTATED	Summary: High-throughput exosome proteomics does not establish extracellular exosome as a core VPS4B localization. Reason: VPS4B is a cytosolic/endosomal ESCRT ATPase involved in exosome biogenesis; HDA exosome detection is not an informative localization for its core function. Supporting Evidence: UniProt:O75351 VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan PMID:24105262 depletion of VPS4B augmented this secretion while not altering the features of EVs.
GO:0005515 protein binding	IPI PMID:14505570 The protein network of HIV budding.	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function. Reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported. Supporting Evidence: file:human/VPS4B/VPS4B-notes.md Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	MARK AS OVER ANNOTATED	Summary: High-throughput exosome proteomics does not establish extracellular exosome as a core VPS4B localization. Reason: VPS4B is a cytosolic/endosomal ESCRT ATPase involved in exosome biogenesis; HDA exosome detection is not an informative localization for its core function. Supporting Evidence: UniProt:O75351 VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan PMID:24105262 depletion of VPS4B augmented this secretion while not altering the features of EVs.
GO:0005829 cytosol	TAS Reactome:R-HSA-3159232	ACCEPT	Summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function. Reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1 PMID:16757520 SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
GO:0005829 cytosol	TAS Reactome:R-HSA-917693	ACCEPT	Summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function. Reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1 PMID:16757520 SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
GO:0005515 protein binding	IPI PMID:19129479 Biochemical analyses of human IST1 and its function in cytok...	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function. Reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported. Supporting Evidence: file:human/VPS4B/VPS4B-notes.md Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0005768 endosome	IDA PMID:11563910 Mammalian cells express two VPS4 proteins both of which are ...	ACCEPT	Summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function. Reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1 PMID:16757520 SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
GO:0016197 endosomal transport	IDA PMID:11563910 Mammalian cells express two VPS4 proteins both of which are ...	ACCEPT	Summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
GO:0016887 ATP hydrolysis activity	IDA PMID:11563910 Mammalian cells express two VPS4 proteins both of which are ...	ACCEPT	Summary: Core VPS4B function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4B and is directly supported by VPS4B biochemical and UniProt evidence. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0005515 protein binding	IPI PMID:16757520 Cholesterol depletion facilitates ubiquitylation of NPC1 and...	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function. Reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported. Supporting Evidence: file:human/VPS4B/VPS4B-notes.md Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0005634 nucleus	IDA PMID:16757520 Cholesterol depletion facilitates ubiquitylation of NPC1 and...	KEEP AS NON CORE	Summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4B molecular role. Reason: Keep as a non-core ESCRT membrane-sealing or nuclear-organization context; VPS4B acts through ESCRT-III remodeling rather than as a nucleus-organization factor per se. Supporting Evidence: PMID:28242692 In mammals, VPS4 depletion induces nuclear morphology defects
GO:0005737 cytoplasm	IDA PMID:16757520 Cholesterol depletion facilitates ubiquitylation of NPC1 and...	ACCEPT	Summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function. Reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1 PMID:16757520 SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
GO:0010008 endosome membrane	IDA PMID:16757520 Cholesterol depletion facilitates ubiquitylation of NPC1 and...	ACCEPT	Summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function. Reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1 PMID:16757520 SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
GO:0032510 endosome to lysosome transport via multivesicular body sorting pathway	IMP PMID:15024011 Role of mammalian vacuolar protein-sorting proteins in endoc...	ACCEPT	Summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:11563910 both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step PMID:15024011 Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
GO:0033993 response to lipid	IDA PMID:16757520 Cholesterol depletion facilitates ubiquitylation of NPC1 and...	MARK AS OVER ANNOTATED	Summary: NPC1/SKD1 response to cholesterol depletion supports ESCRT-endosome involvement, not a core lipid-response function for VPS4B. Reason: The lipid/cholesterol effect is cargo and context dependent; VPS4B core activity is ESCRT-III disassembly. Supporting Evidence: PMID:16757520 SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
GO:0005515 protein binding	IPI PMID:11563910 Mammalian cells express two VPS4 proteins both of which are ...	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function. Reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported. Supporting Evidence: file:human/VPS4B/VPS4B-notes.md Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions. PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
GO:0140545 ATP-dependent protein disaggregase activity	IDA PMID:18687924 Helical structures of ESCRT-III are disassembled by VPS4.	NEW	Summary: Added because direct VPS4B biochemical evidence shows ATP-dependent disassembly of CHMP2A-CHMP3 ESCRT-III tubes, which is more specific than generic ATP hydrolysis activity. Reason: PMID:18687924 directly supports an ATP-dependent protein-complex disassembly activity for VPS4B; this term captures the core molecular function more precisely than protein binding or generic ATP hydrolysis alone. Supporting Evidence: PMID:18687924 the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis. UniProt:O75351 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly UniProt:O75351 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.

📄 View Raw YAML

id: O75351
gene_symbol: VPS4B
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: VPS4B is a conserved AAA-family ATPase that recognizes ESCRT-III assemblies through its MIT domain and uses ATP hydrolysis to remodel and disassemble ESCRT-III polymers. Direct biochemical evidence shows VPS4 binding to and disassembly of CHMP2A-CHMP3 helical tubes upon ATP hydrolysis. This core activity supports endosomal/MVB cargo sorting and related ESCRT membrane-remodeling outputs, including cytokinesis, viral budding, plasma membrane repair, and exosome secretion. The core function is ATP-dependent ESCRT-III remodeling/disassembly rather than generic protein binding or ESCRT-III complex membership.
existing_annotations:
- term:
    id: GO:0016197
    label: endosomal transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function.
    action: ACCEPT
    reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: 'Core VPS4B function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies.'
    action: ACCEPT
    reason: This is the central conserved molecular role of VPS4B and is directly supported by VPS4B biochemical and UniProt evidence.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function.
    action: ACCEPT
    reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
- term:
    id: GO:0090611
    label: obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: The annotation captures a real ubiquitin-independent MVB-sorting context, but the current GO term is obsolete.
    action: MODIFY
    reason: Use a current MVB sorting pathway term rather than retaining an obsolete ubiquitin-independent protein catabolic process term.
    supported_by:
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
    proposed_replacement_terms:
    - id: GO:0071985
      label: multivesicular body sorting pathway
- term:
    id: GO:0000922
    label: spindle pole
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function.
    action: KEEP_AS_NON_CORE
    reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission
    - reference_id: PMID:20616062
      supporting_text: VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Reviewed as peripheral or insufficiently specific relative to the core VPS4B ESCRT ATPase role.
    action: KEEP_AS_NON_CORE
    reason: No direct contradiction was found, but this annotation should not define VPS4B core function.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function.
    action: ACCEPT
    reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
    - reference_id: PMID:16757520
      supporting_text: SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function.
    action: KEEP_AS_NON_CORE
    reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission
    - reference_id: PMID:20616062
      supporting_text: VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
- term:
    id: GO:0006997
    label: nucleus organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4B molecular role.
    action: KEEP_AS_NON_CORE
    reason: Keep as a non-core ESCRT membrane-sealing or nuclear-organization context; VPS4B acts through ESCRT-III remodeling rather than as a nucleus-organization factor per se.
    supported_by:
    - reference_id: PMID:28242692
      supporting_text: In mammals, VPS4 depletion induces nuclear morphology defects
- term:
    id: GO:0007041
    label: lysosomal transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: The broad lysosomal transport annotation reflects VPS4B late-endosomal/MVB trafficking function.
    action: MODIFY
    reason: A more specific late endosome-to-lysosome/MVB sorting pathway term better captures the supported role.
    supported_by:
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
    proposed_replacement_terms:
    - id: GO:0061764
      label: late endosome to lysosome transport via 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: The cell-cycle/centriole annotation overstates downstream phenotypes from VPS4B/ESCRT depletion.
    action: MARK_AS_OVER_ANNOTATED
    reason: Available evidence supports ESCRT-mediated abscission and centrosome/spindle phenotypes, not direct control of this specific cell-cycle regulatory process as a core function.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission
    - reference_id: PMID:20616062
      supporting_text: VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
- term:
    id: GO:0010389
    label: regulation of G2/M transition of mitotic cell cycle
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: The cell-cycle/centriole annotation overstates downstream phenotypes from VPS4B/ESCRT depletion.
    action: MARK_AS_OVER_ANNOTATED
    reason: Available evidence supports ESCRT-mediated abscission and centrosome/spindle phenotypes, not direct control of this specific cell-cycle regulatory process as a core function.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission
    - reference_id: PMID:20616062
      supporting_text: VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: 'Core VPS4B function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies.'
    action: ACCEPT
    reason: This is the central conserved molecular role of VPS4B and is directly supported by VPS4B biochemical and UniProt evidence.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function.
    action: ACCEPT
    reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
    - reference_id: PMID:16757520
      supporting_text: SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
- 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: Directly supported viral/plasma-membrane ESCRT context, but this is host-pathogen exploitation of VPS4B machinery rather than the core cellular function.
    action: KEEP_AS_NON_CORE
    reason: Keep as a real non-core ESCRT output; do not use it to define the primary function of VPS4B.
    supported_by:
    - reference_id: PMID:14505570
      supporting_text: The protein network of HIV budding.
    - reference_id: PMID:17940959
      supporting_text: A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80%
- 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 as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function.
    action: ACCEPT
    reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
- term:
    id: GO:0051261
    label: protein depolymerization
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: VPS4B disassembles ESCRT-III assemblies rather than depolymerizing proteins generally.
    action: MODIFY
    reason: ESCRT III complex disassembly is the specific process supported by VPS4B biochemical evidence.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    proposed_replacement_terms:
    - id: GO:1904903
      label: ESCRT III complex disassembly
- term:
    id: GO:0061952
    label: midbody abscission
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function.
    action: KEEP_AS_NON_CORE
    reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission
    - reference_id: PMID:20616062
      supporting_text: VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
- term:
    id: GO:0090543
    label: Flemming body
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function.
    action: KEEP_AS_NON_CORE
    reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission
    - reference_id: PMID:20616062
      supporting_text: VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
- term:
    id: GO:0090611
    label: obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: The annotation captures a real ubiquitin-independent MVB-sorting context, but the current GO term is obsolete.
    action: MODIFY
    reason: Use a current MVB sorting pathway term rather than retaining an obsolete ubiquitin-independent protein catabolic process term.
    supported_by:
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
    proposed_replacement_terms:
    - id: GO:0071985
      label: multivesicular body sorting pathway
- term:
    id: GO:1903543
    label: positive regulation of exosomal secretion
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Supported positive exosome-release context for VPS4A/B but not the primary cellular function.
    action: KEEP_AS_NON_CORE
    reason: Exosome secretion is one downstream ESCRT-dependent output of VPS4B activity, so retain as non-core.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17928862
  qualifier: enables
  review:
    summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported.
    supported_by:
    - reference_id: file:human/VPS4B/VPS4B-notes.md
      supporting_text: Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported.
    supported_by:
    - reference_id: file:human/VPS4B/VPS4B-notes.md
      supporting_text: Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported.
    supported_by:
    - reference_id: file:human/VPS4B/VPS4B-notes.md
      supporting_text: Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported.
    supported_by:
    - reference_id: file:human/VPS4B/VPS4B-notes.md
      supporting_text: Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported.
    supported_by:
    - reference_id: file:human/VPS4B/VPS4B-notes.md
      supporting_text: Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function.
    action: ACCEPT
    reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
    - reference_id: PMID:16757520
      supporting_text: SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
- term:
    id: GO:0036258
    label: multivesicular body assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function.
    action: ACCEPT
    reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
- term:
    id: GO:0046761
    label: viral budding from plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Directly supported viral/plasma-membrane ESCRT context, but this is host-pathogen exploitation of VPS4B machinery rather than the core cellular function.
    action: KEEP_AS_NON_CORE
    reason: Keep as a real non-core ESCRT output; do not use it to define the primary function of VPS4B.
    supported_by:
    - reference_id: PMID:14505570
      supporting_text: The protein network of HIV budding.
    - reference_id: PMID:17940959
      supporting_text: A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80%
- term:
    id: GO:0061738
    label: late endosomal microautophagy
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Late endosomal microautophagy is plausible for ESCRT machinery, but this specific human VPS4B row is automated/transferred in the local files.
    action: UNDECIDED
    reason: Retain uncertainty pending direct human evidence or a reviewed source tying VPS4B specifically to late endosomal microautophagy.
    supported_by:
    - reference_id: PMID:17428789
      supporting_text: deletion of VPS4 and VPS36 caused impaired maturation of the vacuolar proaminopeptidase I (pAPI) via autophagy or the cytosol to vacuole targeting pathway
    - reference_id: PMID:20588296
      supporting_text: ESCRT-III-mediated membrane neck cleavage is crucial for many processes, including the biogenesis of multivesicular bodies, viral budding, cytokinesis, and probably autophagy.
- term:
    id: GO:0001778
    label: plasma membrane repair
  evidence_type: NAS
  original_reference_id: PMID:24482116
  qualifier: involved_in
  review:
    summary: Supported plasma membrane repair context for ESCRT machinery, retained as a non-core VPS4B output.
    action: KEEP_AS_NON_CORE
    reason: Plasma membrane repair uses ESCRT-mediated shedding/fission but is a specialized context of the core ESCRT remodeling machinery.
    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.
- term:
    id: GO:0005643
    label: nuclear pore
  evidence_type: NAS
  original_reference_id: PMID:16505166
  qualifier: part_of
  review:
    summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4B molecular role.
    action: KEEP_AS_NON_CORE
    reason: Keep as a non-core ESCRT membrane-sealing or nuclear-organization context; VPS4B acts through ESCRT-III remodeling rather than as a nucleus-organization factor per se.
    supported_by:
    - reference_id: PMID:28242692
      supporting_text: In mammals, VPS4 depletion induces nuclear morphology defects
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: NAS
  original_reference_id: PMID:19234443
  qualifier: located_in
  review:
    summary: Directly supported viral/plasma-membrane ESCRT context, but this is host-pathogen exploitation of VPS4B machinery rather than the core cellular function.
    action: KEEP_AS_NON_CORE
    reason: Keep as a real non-core ESCRT output; do not use it to define the primary function of VPS4B.
    supported_by:
    - reference_id: PMID:14505570
      supporting_text: The protein network of HIV budding.
    - reference_id: PMID:17940959
      supporting_text: A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80%
- term:
    id: GO:0006914
    label: autophagy
  evidence_type: NAS
  original_reference_id: PMID:17428789
  qualifier: involved_in
  review:
    summary: Autophagy connection is plausible for ESCRT machinery, but the local cached evidence for this specific VPS4B annotation is yeast-only or review-level rather than direct human VPS4B evidence.
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation overstates direct evidence for human VPS4B in macroautophagy/autophagosome maturation. The core supported role remains ESCRT-III disassembly and membrane remodeling.
    supported_by:
    - reference_id: PMID:17428789
      supporting_text: deletion of VPS4 and VPS36 caused impaired maturation of the vacuolar proaminopeptidase I (pAPI) via autophagy or the cytosol to vacuole targeting pathway
    - reference_id: PMID:20588296
      supporting_text: ESCRT-III-mediated membrane neck cleavage is crucial for many processes, including the biogenesis of multivesicular bodies, viral budding, cytokinesis, and probably autophagy.
- term:
    id: GO:0006997
    label: nucleus organization
  evidence_type: NAS
  original_reference_id: PMID:20616062
  qualifier: involved_in
  review:
    summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4B molecular role.
    action: KEEP_AS_NON_CORE
    reason: Keep as a non-core ESCRT membrane-sealing or nuclear-organization context; VPS4B acts through ESCRT-III remodeling rather than as a nucleus-organization factor per se.
    supported_by:
    - reference_id: PMID:28242692
      supporting_text: In mammals, VPS4 depletion induces nuclear morphology defects
- term:
    id: GO:0030496
    label: midbody
  evidence_type: NAS
  original_reference_id: PMID:26040712
  qualifier: located_in
  review:
    summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function.
    action: KEEP_AS_NON_CORE
    reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission
    - reference_id: PMID:20616062
      supporting_text: VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
- term:
    id: GO:0031468
    label: nuclear membrane reassembly
  evidence_type: NAS
  original_reference_id: PMID:26040713
  qualifier: involved_in
  review:
    summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4B molecular role.
    action: KEEP_AS_NON_CORE
    reason: Keep as a non-core ESCRT membrane-sealing or nuclear-organization context; VPS4B acts through ESCRT-III remodeling rather than as a nucleus-organization factor per se.
    supported_by:
    - reference_id: PMID:28242692
      supporting_text: In mammals, VPS4 depletion induces nuclear morphology defects
- term:
    id: GO:0036258
    label: multivesicular body assembly
  evidence_type: NAS
  original_reference_id: PMID:16505166
  qualifier: involved_in
  review:
    summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function.
    action: ACCEPT
    reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
- term:
    id: GO:0046761
    label: viral budding from plasma membrane
  evidence_type: IMP
  original_reference_id: PMID:16193069
  qualifier: involved_in
  review:
    summary: Directly supported viral/plasma-membrane ESCRT context, but this is host-pathogen exploitation of VPS4B machinery rather than the core cellular function.
    action: KEEP_AS_NON_CORE
    reason: Keep as a real non-core ESCRT output; do not use it to define the primary function of VPS4B.
    supported_by:
    - reference_id: PMID:14505570
      supporting_text: The protein network of HIV budding.
    - reference_id: PMID:17940959
      supporting_text: A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80%
- term:
    id: GO:0061764
    label: late endosome to lysosome transport via multivesicular body sorting pathway
  evidence_type: NAS
  original_reference_id: PMID:9211789
  qualifier: involved_in
  review:
    summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function.
    action: ACCEPT
    reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
- term:
    id: GO:0061952
    label: midbody abscission
  evidence_type: NAS
  original_reference_id: PMID:20616062
  qualifier: involved_in
  review:
    summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function.
    action: KEEP_AS_NON_CORE
    reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission
    - reference_id: PMID:20616062
      supporting_text: VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
- term:
    id: GO:0071985
    label: multivesicular body sorting pathway
  evidence_type: NAS
  original_reference_id: PMID:16505166
  qualifier: involved_in
  review:
    summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function.
    action: ACCEPT
    reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
- term:
    id: GO:0090148
    label: membrane fission
  evidence_type: NAS
  original_reference_id: PMID:19234443
  qualifier: involved_in
  review:
    summary: Supported as an ESCRT/VPS4 membrane-remodeling output, with direct VPS4B disassembly evidence and broader ESCRT membrane-fission support.
    action: ACCEPT
    reason: VPS4B-controlled ESCRT-III polymer remodeling supports membrane-neck constriction/fission in MVB and related pathways.
    supported_by:
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
- term:
    id: GO:0097352
    label: autophagosome maturation
  evidence_type: NAS
  original_reference_id: PMID:9211789
  qualifier: involved_in
  review:
    summary: Autophagy connection is plausible for ESCRT machinery, but the local cached evidence for this specific VPS4B annotation is yeast-only or review-level rather than direct human VPS4B evidence.
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation overstates direct evidence for human VPS4B in macroautophagy/autophagosome maturation. The core supported role remains ESCRT-III disassembly and membrane remodeling.
    supported_by:
    - reference_id: PMID:17428789
      supporting_text: deletion of VPS4 and VPS36 caused impaired maturation of the vacuolar proaminopeptidase I (pAPI) via autophagy or the cytosol to vacuole targeting pathway
    - reference_id: PMID:20588296
      supporting_text: ESCRT-III-mediated membrane neck cleavage is crucial for many processes, including the biogenesis of multivesicular bodies, viral budding, cytokinesis, and probably autophagy.
- term:
    id: GO:1904949
    label: ATPase complex
  evidence_type: NAS
  original_reference_id: PMID:19278657
  qualifier: part_of
  review:
    summary: 'Core VPS4B function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies.'
    action: ACCEPT
    reason: This is the central conserved molecular role of VPS4B and is directly supported by VPS4B biochemical and UniProt evidence.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function.
    action: ACCEPT
    reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
    - reference_id: PMID:16757520
      supporting_text: SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
- term:
    id: GO:0046761
    label: viral budding from plasma membrane
  evidence_type: IMP
  original_reference_id: PMID:14505570
  qualifier: involved_in
  review:
    summary: Directly supported viral/plasma-membrane ESCRT context, but this is host-pathogen exploitation of VPS4B machinery rather than the core cellular function.
    action: KEEP_AS_NON_CORE
    reason: Keep as a real non-core ESCRT output; do not use it to define the primary function of VPS4B.
    supported_by:
    - reference_id: PMID:14505570
      supporting_text: The protein network of HIV budding.
    - reference_id: PMID:17940959
      supporting_text: A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80%
- term:
    id: GO:0046761
    label: viral budding from plasma membrane
  evidence_type: IMP
  original_reference_id: PMID:17940959
  qualifier: involved_in
  review:
    summary: Directly supported viral/plasma-membrane ESCRT context, but this is host-pathogen exploitation of VPS4B machinery rather than the core cellular function.
    action: KEEP_AS_NON_CORE
    reason: Keep as a real non-core ESCRT output; do not use it to define the primary function of VPS4B.
    supported_by:
    - reference_id: PMID:14505570
      supporting_text: The protein network of HIV budding.
    - reference_id: PMID:17940959
      supporting_text: A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80%
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IDA
  original_reference_id: PMID:18687924
  qualifier: enables
  review:
    summary: 'Core VPS4B function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies.'
    action: ACCEPT
    reason: This is the central conserved molecular role of VPS4B and is directly supported by VPS4B biochemical and UniProt evidence.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18687924
  qualifier: enables
  review:
    summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported.
    supported_by:
    - reference_id: file:human/VPS4B/VPS4B-notes.md
      supporting_text: Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0044877
    label: protein-containing complex binding
  evidence_type: IDA
  original_reference_id: PMID:18687924
  qualifier: enables
  review:
    summary: 'Core VPS4B function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies.'
    action: ACCEPT
    reason: This is the central conserved molecular role of VPS4B and is directly supported by VPS4B biochemical and UniProt evidence.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:1904903
    label: ESCRT III complex disassembly
  evidence_type: IDA
  original_reference_id: PMID:18687924
  qualifier: involved_in
  review:
    summary: 'Core VPS4B function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies.'
    action: ACCEPT
    reason: This is the central conserved molecular role of VPS4B and is directly supported by VPS4B biochemical and UniProt evidence.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0061952
    label: midbody abscission
  evidence_type: IMP
  original_reference_id: PMID:20616062
  qualifier: involved_in
  review:
    summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function.
    action: KEEP_AS_NON_CORE
    reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission
    - reference_id: PMID:20616062
      supporting_text: VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
- term:
    id: GO:0016236
    label: macroautophagy
  evidence_type: NAS
  original_reference_id: PMID:20588296
  qualifier: involved_in
  review:
    summary: Autophagy connection is plausible for ESCRT machinery, but the local cached evidence for this specific VPS4B annotation is yeast-only or review-level rather than direct human VPS4B evidence.
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation overstates direct evidence for human VPS4B in macroautophagy/autophagosome maturation. The core supported role remains ESCRT-III disassembly and membrane remodeling.
    supported_by:
    - reference_id: PMID:17428789
      supporting_text: deletion of VPS4 and VPS36 caused impaired maturation of the vacuolar proaminopeptidase I (pAPI) via autophagy or the cytosol to vacuole targeting pathway
    - reference_id: PMID:20588296
      supporting_text: ESCRT-III-mediated membrane neck cleavage is crucial for many processes, including the biogenesis of multivesicular bodies, viral budding, cytokinesis, and probably autophagy.
- term:
    id: GO:0036258
    label: multivesicular body assembly
  evidence_type: NAS
  original_reference_id: PMID:20588296
  qualifier: involved_in
  review:
    summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function.
    action: ACCEPT
    reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
- term:
    id: GO:1904903
    label: ESCRT III complex disassembly
  evidence_type: NAS
  original_reference_id: PMID:20588296
  qualifier: involved_in
  review:
    summary: 'Core VPS4B function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies.'
    action: ACCEPT
    reason: This is the central conserved molecular role of VPS4B and is directly supported by VPS4B biochemical and UniProt evidence.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18385515
  qualifier: enables
  review:
    summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported.
    supported_by:
    - reference_id: file:human/VPS4B/VPS4B-notes.md
      supporting_text: Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23105106
  qualifier: enables
  review:
    summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported.
    supported_by:
    - reference_id: file:human/VPS4B/VPS4B-notes.md
      supporting_text: Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16193069
  qualifier: enables
  review:
    summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported.
    supported_by:
    - reference_id: file:human/VPS4B/VPS4B-notes.md
      supporting_text: Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IDA
  original_reference_id: PMID:16193069
  qualifier: enables
  review:
    summary: Identical protein binding is too generic and does not capture the VPS4B oligomeric ATPase mechanism.
    action: MARK_AS_OVER_ANNOTATED
    reason: VPS4B oligomerization is better discussed as part of ATPase assembly and ESCRT-III disassembly, not as a standalone identical-protein-binding function.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:16193069
  qualifier: enables
  review:
    summary: VPS4B oligomerization is a real mechanistic property of the ATPase but not an informative core molecular function by itself.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because VPS4B forms ATP-dependent oligomeric assemblies, while the core function is ATP-dependent ESCRT-III disassembly.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
- term:
    id: GO:0051261
    label: protein depolymerization
  evidence_type: IDA
  original_reference_id: PMID:18687924
  qualifier: involved_in
  review:
    summary: VPS4B disassembles ESCRT-III assemblies rather than depolymerizing proteins generally.
    action: MODIFY
    reason: ESCRT III complex disassembly is the specific process supported by VPS4B biochemical evidence.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    proposed_replacement_terms:
    - id: GO:1904903
      label: ESCRT III complex disassembly
- term:
    id: GO:0000922
    label: spindle pole
  evidence_type: IDA
  original_reference_id: PMID:20616062
  qualifier: located_in
  review:
    summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function.
    action: KEEP_AS_NON_CORE
    reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission
    - reference_id: PMID:20616062
      supporting_text: VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:20616062
  qualifier: located_in
  review:
    summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4B molecular role.
    action: KEEP_AS_NON_CORE
    reason: Keep as a non-core ESCRT membrane-sealing or nuclear-organization context; VPS4B acts through ESCRT-III remodeling rather than as a nucleus-organization factor per se.
    supported_by:
    - reference_id: PMID:28242692
      supporting_text: In mammals, VPS4 depletion induces nuclear morphology defects
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:20616062
  qualifier: located_in
  review:
    summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function.
    action: ACCEPT
    reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
    - reference_id: PMID:16757520
      supporting_text: SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IDA
  original_reference_id: PMID:20616062
  qualifier: located_in
  review:
    summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function.
    action: KEEP_AS_NON_CORE
    reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission
    - reference_id: PMID:20616062
      supporting_text: VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
- term:
    id: GO:0006997
    label: nucleus organization
  evidence_type: IMP
  original_reference_id: PMID:20616062
  qualifier: involved_in
  review:
    summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4B molecular role.
    action: KEEP_AS_NON_CORE
    reason: Keep as a non-core ESCRT membrane-sealing or nuclear-organization context; VPS4B acts through ESCRT-III remodeling rather than as a nucleus-organization factor per se.
    supported_by:
    - reference_id: PMID:28242692
      supporting_text: In mammals, VPS4 depletion induces nuclear morphology defects
- term:
    id: GO:0007080
    label: mitotic metaphase chromosome alignment
  evidence_type: IMP
  original_reference_id: PMID:20616062
  qualifier: involved_in
  review:
    summary: The cell-cycle/centriole annotation overstates downstream phenotypes from VPS4B/ESCRT depletion.
    action: MARK_AS_OVER_ANNOTATED
    reason: Available evidence supports ESCRT-mediated abscission and centrosome/spindle phenotypes, not direct control of this specific cell-cycle regulatory process as a core function.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission
    - reference_id: PMID:20616062
      supporting_text: VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
- term:
    id: GO:0010824
    label: regulation of centrosome duplication
  evidence_type: IMP
  original_reference_id: PMID:20616062
  qualifier: involved_in
  review:
    summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function.
    action: KEEP_AS_NON_CORE
    reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission
    - reference_id: PMID:20616062
      supporting_text: VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
- term:
    id: GO:0010971
    label: positive regulation of G2/M transition of mitotic cell cycle
  evidence_type: IMP
  original_reference_id: PMID:20616062
  qualifier: involved_in
  review:
    summary: The cell-cycle/centriole annotation overstates downstream phenotypes from VPS4B/ESCRT depletion.
    action: MARK_AS_OVER_ANNOTATED
    reason: Available evidence supports ESCRT-mediated abscission and centrosome/spindle phenotypes, not direct control of this specific cell-cycle regulatory process as a core function.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission
    - reference_id: PMID:20616062
      supporting_text: VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
- term:
    id: GO:0090543
    label: Flemming body
  evidence_type: IDA
  original_reference_id: PMID:20616062
  qualifier: located_in
  review:
    summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function.
    action: KEEP_AS_NON_CORE
    reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission
    - reference_id: PMID:20616062
      supporting_text: VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
- term:
    id: GO:1901673
    label: regulation of mitotic spindle assembly
  evidence_type: IMP
  original_reference_id: PMID:20616062
  qualifier: involved_in
  review:
    summary: Supported cell-division or centrosome/spindle context for VPS4B, downstream of its ESCRT ATPase function.
    action: KEEP_AS_NON_CORE
    reason: This is a bona fide VPS4B cellular context but is non-core relative to the conserved ATP-dependent ESCRT-III remodeling function.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission
    - reference_id: PMID:20616062
      supporting_text: VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
- term:
    id: GO:1903724
    label: positive regulation of centriole elongation
  evidence_type: IMP
  original_reference_id: PMID:20616062
  qualifier: involved_in
  review:
    summary: The cell-cycle/centriole annotation overstates downstream phenotypes from VPS4B/ESCRT depletion.
    action: MARK_AS_OVER_ANNOTATED
    reason: Available evidence supports ESCRT-mediated abscission and centrosome/spindle phenotypes, not direct control of this specific cell-cycle regulatory process as a core function.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission
    - reference_id: PMID:20616062
      supporting_text: VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis
- 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: The annotation captures a real ubiquitin-independent MVB-sorting context, but the current GO term is obsolete.
    action: MODIFY
    reason: Use a current MVB sorting pathway term rather than retaining an obsolete ubiquitin-independent protein catabolic process term.
    supported_by:
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
    proposed_replacement_terms:
    - id: GO:0071985
      label: multivesicular body sorting pathway
- term:
    id: GO:1903543
    label: positive regulation of exosomal secretion
  evidence_type: IMP
  original_reference_id: PMID:22660413
  qualifier: involved_in
  review:
    summary: Supported positive exosome-release context for VPS4A/B but not the primary cellular function.
    action: KEEP_AS_NON_CORE
    reason: Exosome secretion is one downstream ESCRT-dependent output of VPS4B activity, so retain as non-core.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan
- term:
    id: GO:1903542
    label: negative regulation of exosomal secretion
  evidence_type: IMP
  original_reference_id: PMID:24105262
  qualifier: involved_in
  review:
    summary: Supported context-dependent negative regulation of EV secretion in a HeLa-CIITA RNAi screen.
    action: KEEP_AS_NON_CORE
    reason: This exosome phenotype is cell/cargo-context dependent and non-core relative to ATP-dependent ESCRT-III disassembly.
    supported_by:
    - reference_id: PMID:24105262
      supporting_text: depletion of VPS4B augmented this secretion while not altering the features of EVs.
- term:
    id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  evidence_type: IMP
  original_reference_id: PMID:22547407
  qualifier: involved_in
  review:
    summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function.
    action: ACCEPT
    reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: IGI
  original_reference_id: PMID:24107264
  qualifier: involved_in
  review:
    summary: Directly supported viral/plasma-membrane ESCRT context, but this is host-pathogen exploitation of VPS4B machinery rather than the core cellular function.
    action: KEEP_AS_NON_CORE
    reason: Keep as a real non-core ESCRT output; do not use it to define the primary function of VPS4B.
    supported_by:
    - reference_id: PMID:14505570
      supporting_text: The protein network of HIV budding.
    - reference_id: PMID:17940959
      supporting_text: A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80%
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  qualifier: located_in
  review:
    summary: High-throughput exosome proteomics does not establish extracellular exosome as a core VPS4B localization.
    action: MARK_AS_OVER_ANNOTATED
    reason: VPS4B is a cytosolic/endosomal ESCRT ATPase involved in exosome biogenesis; HDA exosome detection is not an informative localization for its core function.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan
    - reference_id: PMID:24105262
      supporting_text: depletion of VPS4B augmented this secretion while not altering the features of EVs.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14505570
  qualifier: enables
  review:
    summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported.
    supported_by:
    - reference_id: file:human/VPS4B/VPS4B-notes.md
      supporting_text: Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  qualifier: located_in
  review:
    summary: High-throughput exosome proteomics does not establish extracellular exosome as a core VPS4B localization.
    action: MARK_AS_OVER_ANNOTATED
    reason: VPS4B is a cytosolic/endosomal ESCRT ATPase involved in exosome biogenesis; HDA exosome detection is not an informative localization for its core function.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan
    - reference_id: PMID:24105262
      supporting_text: depletion of VPS4B augmented this secretion while not altering the features of EVs.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3159232
  qualifier: located_in
  review:
    summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function.
    action: ACCEPT
    reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
    - reference_id: PMID:16757520
      supporting_text: SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-917693
  qualifier: located_in
  review:
    summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function.
    action: ACCEPT
    reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
    - reference_id: PMID:16757520
      supporting_text: SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19129479
  qualifier: enables
  review:
    summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported.
    supported_by:
    - reference_id: file:human/VPS4B/VPS4B-notes.md
      supporting_text: Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IDA
  original_reference_id: PMID:11563910
  qualifier: located_in
  review:
    summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function.
    action: ACCEPT
    reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
    - reference_id: PMID:16757520
      supporting_text: SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
- term:
    id: GO:0016197
    label: endosomal transport
  evidence_type: IDA
  original_reference_id: PMID:11563910
  qualifier: acts_upstream_of_or_within
  review:
    summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function.
    action: ACCEPT
    reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IDA
  original_reference_id: PMID:11563910
  qualifier: enables
  review:
    summary: 'Core VPS4B function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies.'
    action: ACCEPT
    reason: This is the central conserved molecular role of VPS4B and is directly supported by VPS4B biochemical and UniProt evidence.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16757520
  qualifier: enables
  review:
    summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported.
    supported_by:
    - reference_id: file:human/VPS4B/VPS4B-notes.md
      supporting_text: Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:16757520
  qualifier: located_in
  review:
    summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4B molecular role.
    action: KEEP_AS_NON_CORE
    reason: Keep as a non-core ESCRT membrane-sealing or nuclear-organization context; VPS4B acts through ESCRT-III remodeling rather than as a nucleus-organization factor per se.
    supported_by:
    - reference_id: PMID:28242692
      supporting_text: In mammals, VPS4 depletion induces nuclear morphology defects
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:16757520
  qualifier: located_in
  review:
    summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function.
    action: ACCEPT
    reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
    - reference_id: PMID:16757520
      supporting_text: SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: IDA
  original_reference_id: PMID:16757520
  qualifier: located_in
  review:
    summary: Supported localization for a cytosolic AAA ATPase recruited to endosomal/late-endosomal membranes during ESCRT function.
    action: ACCEPT
    reason: These compartments match the core VPS4B endosomal/MVB sorting and ESCRT-disassembly role.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
    - reference_id: PMID:16757520
      supporting_text: SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
- term:
    id: GO:0032510
    label: endosome to lysosome transport via multivesicular body sorting pathway
  evidence_type: IMP
  original_reference_id: PMID:15024011
  qualifier: involved_in
  review:
    summary: Supported as part of the core VPS4B endosomal/MVB sorting and ESCRT-recycling function.
    action: ACCEPT
    reason: VPS4B ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport.
    supported_by:
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:11563910
      supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
    - reference_id: PMID:15024011
      supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
- term:
    id: GO:0033993
    label: response to lipid
  evidence_type: IDA
  original_reference_id: PMID:16757520
  qualifier: involved_in
  review:
    summary: NPC1/SKD1 response to cholesterol depletion supports ESCRT-endosome involvement, not a core lipid-response function for VPS4B.
    action: MARK_AS_OVER_ANNOTATED
    reason: The lipid/cholesterol effect is cargo and context dependent; VPS4B core activity is ESCRT-III disassembly.
    supported_by:
    - reference_id: PMID:16757520
      supporting_text: SKD1(E235Q), a dominant-negative mutant of SKD1/Vps4 that inhibits disassembly of the endosomal sorting complex required for transport (ESCRT), caused an accumulation of ubiquitylated NPC1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11563910
  qualifier: enables
  review:
    summary: The underlying interaction may be useful context, but GO:0005515 is too generic to describe VPS4B molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: VPS4B function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and protein-containing complex binding where supported.
    supported_by:
    - reference_id: file:human/VPS4B/VPS4B-notes.md
      supporting_text: Generic `GO:0005515 protein binding` rows should not be retained as informative molecular functions.
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: PMID:18606141
      supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- term:
    id: GO:0140545
    label: ATP-dependent protein disaggregase activity
  evidence_type: IDA
  original_reference_id: PMID:18687924
  qualifier: enables
  review:
    summary: Added because direct VPS4B biochemical evidence shows ATP-dependent disassembly of CHMP2A-CHMP3 ESCRT-III tubes, which is more specific than generic ATP hydrolysis activity.
    action: NEW
    reason: PMID:18687924 directly supports an ATP-dependent protein-complex disassembly activity for VPS4B; this term captures the core molecular function more precisely than protein binding or generic ATP hydrolysis alone.
    supported_by:
    - reference_id: PMID:18687924
      supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
    - reference_id: UniProt:O75351
      supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
    - reference_id: UniProt:O75351
      supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  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:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  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:11563910
  title: Mammalian cells express two VPS4 proteins both of which are involved in intracellular protein trafficking.
  findings:
  - statement: Human VPS4A and VPS4B are involved in late endosomal protein transport; ATPase-domain mutants cause dominant-negative sorting defects.
- id: PMID:14505570
  title: The protein network of HIV budding.
  findings: []
- id: PMID:15024011
  title: Role of mammalian vacuolar protein-sorting proteins in endocytic trafficking of a non-ubiquitinated G protein-coupled receptor to lysosomes.
  findings:
  - statement: Dominant-negative Vps4/Skd1 inhibits lysosomal trafficking of a non-ubiquitinated GPCR, supporting endosome-to-lysosome/MVB sorting.
- id: PMID:16193069
  title: Structural and mechanistic studies of VPS4 proteins.
  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:16757520
  title: Cholesterol depletion facilitates ubiquitylation of NPC1 and its association with SKD1/Vps4.
  findings:
  - statement: NPC1 ubiquitylation and association with SKD1/Vps4 respond to cholesterol depletion, supporting endosomal ESCRT context but not a core lipid-response function.
- id: PMID:17428789
  title: Phosphatidylethanolamine, a limiting factor of autophagy in yeast strains bearing a defect in the carboxypeptidase Y pathway of vacuolar targeting.
  findings: []
- id: PMID:17928862
  title: ESCRT-III recognition by VPS4 ATPases.
  findings: []
- id: PMID:17940959
  title: Involvement of vacuolar protein sorting pathway in Ebola virus release independent of TSG101 interaction.
  findings: []
- id: PMID:18385515
  title: Novel interactions of ESCRT-III with LIP5 and VPS4 and their implications for ESCRT-III disassembly.
  findings: []
- id: PMID:18606141
  title: Two distinct modes of ESCRT-III recognition are required for VPS4 functions in lysosomal protein targeting and HIV-1 budding.
  findings:
  - statement: VPS4 MIT-domain interactions with ESCRT-III MIM motifs support VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
- id: PMID:18687924
  title: Helical structures of ESCRT-III are disassembled by VPS4.
  findings:
  - statement: VPS4 binds and ATP-dependently disassembles CHMP2A-CHMP3 helical ESCRT-III tubes, directly supporting VPS4B ESCRT-III disassembly activity.
- id: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings: []
- id: PMID:19129479
  title: Biochemical analyses of human IST1 and its function in cytokinesis.
  findings: []
- id: PMID:19234443
  title: Membrane scission by the ESCRT-III complex.
  findings: []
- id: PMID:19278657
  title: 'Three-dimensional structure of AAA ATPase Vps4: advancing structural insights into the mechanisms of endosomal sorting and enveloped virus budding.'
  findings: []
- id: PMID:20588296
  title: 'Membrane budding and scission by the ESCRT machinery: it''s all in the neck.'
  findings:
  - statement: Review-level ESCRT/autophagy statements are treated cautiously because they do not directly establish human VPS4B macroautophagy as a core function.
- id: PMID:20616062
  title: Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance.
  findings:
  - statement: VPS4A/B and ESCRT-III depletion affects abscission, centrosomes, and spindle poles; these are retained as non-core cell-division contexts.
- id: PMID:22547407
  title: ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting.
  findings: []
- id: PMID:22660413
  title: Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.
  findings: []
- id: PMID:23105106
  title: Interactions of the human LIP5 regulatory protein with endosomal sorting complexes required for transport.
  findings: []
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
  findings: []
- id: PMID:24105262
  title: Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles.
  findings:
  - statement: VPS4B depletion increased EV-associated CD63 and MHC II secretion in a HeLa-CIITA screen, supporting a context-dependent exosome phenotype.
- 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:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- 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:28242692
  title: LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope closure in fission yeast and human cells.
  findings:
  - statement: ESCRT-III/VPS4 activity is linked to nuclear-envelope repair and morphology; this supports a non-core nuclear-envelope context for VPS4B.
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
  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:9211789
  title: The VPS4 gene is involved in protein transport out of a yeast pre-vacuolar endosome-like compartment.
  findings: []
- id: Reactome:R-HSA-3159232
  title: Recruitment Of HIV Virion Budding Machinery
  findings: []
- id: Reactome:R-HSA-917693
  title: ESCRT Disassembly
  findings: []
- id: UniProt:O75351
  title: UniProt entry for VPS4B (O75351)
  findings:
  - statement: VPS4B is an AAA ATPase that recognizes and ATP-dependently disassembles ESCRT-III assemblies for further rounds of MVB sorting.
- id: file:human/VPS4B/VPS4B-notes.md
  title: Local curation notes for VPS4B
  findings:
  - statement: Local synthesis identifies ATP-dependent ESCRT-III remodeling/disassembly as the core VPS4B function and treats PN autophagy rows as context unless directly supported.
core_functions:
- description: ATP-dependent remodeling and disassembly of ESCRT-III assemblies during endosomal/MVB sorting and related ESCRT membrane-remodeling events.
  supported_by:
  - reference_id: UniProt:O75351
    supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
  - reference_id: UniProt:O75351
    supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
  - reference_id: PMID:18687924
    supporting_text: the AAA-type adenosine triphosphatase VPS4 could bind on the inside of the tubule and disassemble the tubes upon adenosine triphosphate hydrolysis.
  - reference_id: PMID:18606141
    supporting_text: Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding.
  molecular_function:
    id: GO:0140545
    label: ATP-dependent protein disaggregase activity
  directly_involved_in:
  - id: GO:1904903
    label: ESCRT III complex disassembly
  - id: GO:0090148
    label: membrane fission
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0010008
    label: endosome membrane
  - id: GO:0031902
    label: late endosome membrane
- description: ESCRT-dependent endosomal cargo sorting and multivesicular-body/intralumenal-vesicle biogenesis.
  supported_by:
  - reference_id: PMID:11563910
    supporting_text: both human VPS4 proteins are involved in intracellular protein trafficking, presumably at a late endosomal protein transport step
  - reference_id: PMID:15024011
    supporting_text: Agonist-induced proteolysis of DOR was significantly inhibited by dominant negative mutant versions of Vps4/Skd1
  - reference_id: UniProt:O75351
    supporting_text: Recognizes membrane-associated ESCRT-III assemblies and catalyzes their ATP-dependent disassembly
  - reference_id: UniProt:O75351
    supporting_text: Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting.
  molecular_function:
    id: GO:0016887
    label: ATP hydrolysis activity
  directly_involved_in:
  - id: GO:0016197
    label: endosomal transport
  - id: GO:0036258
    label: multivesicular body assembly
  - id: GO:0071985
    label: multivesicular body sorting pathway
  - id: GO:0032510
    label: endosome to lysosome transport via multivesicular body sorting pathway
  - id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  locations:
  - id: GO:0005768
    label: endosome
  - id: GO:0005829
    label: cytosol
  - id: GO:0031902
    label: late endosome membrane
suggested_questions:
- question: Which ESCRT-dependent contexts require VPS4B specifically rather than VPS4A or mixed VPS4A/VPS4B assemblies?
- question: Does VPS4B have direct human-cell roles in phagophore closure or late endosomal microautophagy beyond its generic ESCRT-III disassembly function?
- question: How do VPS4B-specific regulators such as VTA1 and ZFYVE19/ANCHR tune ATPase assembly, ESCRT-III turnover, and context-specific membrane remodeling?
suggested_experiments:
- description: Use rescue assays after VPS4A/VPS4B depletion with VPS4B wild-type, ATPase-dead, MIT-interface, and VTA1-binding mutants across MVB sorting, cytokinesis, exosome, and autophagy assays.
  hypothesis: VPS4B ATPase activity, ESCRT-III recognition, and VTA1-dependent regulation make separable contributions to different ESCRT-dependent cellular contexts.
- description: Measure endogenous VPS4B recruitment and ESCRT-III turnover during phagophore closure or late endosomal microautophagy with live imaging and acute VPS4B-specific perturbation.
  hypothesis: If VPS4B has a direct autophagy role, it should be transiently recruited to the relevant membrane and required for ESCRT-III turnover there.
- description: Compare VPS4A and VPS4B ATP-dependent disassembly kinetics on defined CHMP2A-CHMP3 and mixed ESCRT-III polymers in vitro.
  hypothesis: VPS4B shares the conserved ESCRT-III disassembly mechanism but may differ from VPS4A in substrate preference, VTA1 response, or assembly kinetics.

Gene Description

Existing Annotations Review

Core Functions

ATP-dependent remodeling and disassembly of ESCRT-III assemblies during endosomal/MVB sorting and related ESCRT membrane-remodeling events.

ESCRT-dependent endosomal cargo sorting and multivesicular-body/intralumenal-vesicle biogenesis.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

VPS4B notes

Local evidence reviewed

Curation synthesis

Pn Notes

VPS4B PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | ESCRT-III complex activity modulator

PN row 2: Autophagy-Lysosome Pathway | Microautophagy | General microautophagy machinery | ESCRT-III complex component

Projected GO annotations (2)

Note

📄 View Raw YAML