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.
| 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. |
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Download this section (compressed HTML)Q: Which ESCRT-dependent contexts require VPS4B specifically rather than VPS4A or mixed VPS4A/VPS4B assemblies?
Q: Does VPS4B have direct human-cell roles in phagophore closure or late endosomal microautophagy beyond its generic ESCRT-III disassembly function?
Q: How do VPS4B-specific regulators such as VTA1 and ZFYVE19/ANCHR tune ATPase assembly, ESCRT-III turnover, and context-specific membrane remodeling?
Experiment: 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.
Experiment: 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.
Experiment: 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.
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