VPS4A is a conserved AAA-family ATPase that recognizes membrane-associated ESCRT-III assemblies through its MIT domain and uses ATP hydrolysis to remodel and disassemble ESCRT-III polymers. This recycling function supports ESCRT-dependent membrane remodeling in MVB/endosomal cargo sorting and related topologically equivalent events, including cytokinetic abscission, nuclear-envelope sealing, viral budding, plasma membrane repair, and exosome release. The core function is ATP-driven ESCRT-III remodeling/disassembly rather than generic protein binding or membership in the ESCRT-III complex itself.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0016197 endosomal transport | IBA GO_REF:0000033 | ACCEPT | Summary: Supported as part of the core VPS4A endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4A ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0016887 ATP hydrolysis activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core VPS4A function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4A and directly supports ESCRT recycling and downstream membrane remodeling. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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 VPS4A endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4A ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| 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:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0000922 spindle pole | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Supported cell-division or midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: Accept ATP binding as part of the core AAA ATPase mechanism that enables VPS4A ATP hydrolysis and ESCRT-III remodeling. Reason: ATP binding is a mechanistic prerequisite for the accepted ATP hydrolysis and ATP-dependent protein-disaggregase activity of VPS4A; it is less specific than hydrolysis but consistent with the core ATPase function. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly |
| GO:0005813 centrosome | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Supported cell-division or midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| GO:0005819 spindle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Supported cell-division or midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| GO:0006997 nucleus organization | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4A molecular role. Reason: Keep as a non-core ESCRT membrane-sealing context; VPS4A 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 VPS4A late-endosomal/MVB trafficking function. Reason: A more specific late endosome-to-lysosome/MVB sorting pathway term better captures the evidence. Proposed replacements: late endosome to lysosome transport via multivesicular body sorting pathway Supporting Evidence: PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0007080 mitotic metaphase chromosome alignment | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: VPS4A/ESCRT depletion can perturb spindle and chromosome phenotypes, but this does not show VPS4A is a metaphase chromosome-alignment factor. Reason: The term overstates a downstream cell-division phenotype relative to the direct ESCRT/VPS4 mechanism. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| GO:0010389 regulation of G2/M transition of mitotic cell cycle | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: The automated G2/M-transition annotation is too broad and indirect for VPS4A. Reason: Available evidence supports ESCRT-mediated abscission and membrane remodeling, not direct regulation of the G2/M transition. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000120 | ACCEPT | Summary: Core VPS4A function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4A and directly supports ESCRT recycling and downstream membrane remodeling. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. |
| GO:0030496 midbody | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Supported cell-division or midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| GO:0031902 late endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| 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 VPS4A 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 VPS4A. Supporting Evidence: PMID:11595185 Dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 and MLV 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 VPS4A endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4A ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0051261 protein depolymerization | IEA GO_REF:0000117 | MODIFY | Summary: VPS4A depolymerizes/remodels ESCRT-III assemblies rather than depolymerizing proteins generally. Reason: ESCRT III complex disassembly is the specific process supported by the VPS4A mechanism. Proposed replacements: ESCRT III complex disassembly Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. |
| GO:0061952 midbody abscission | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Supported cell-division or midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| GO:0090543 Flemming body | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Supported cell-division or midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| 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:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:1903543 positive regulation of exosomal secretion | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Supported exosome-release context for VPS4A/B but not the primary cellular function. Reason: Exosome secretion is one downstream ESCRT-dependent output of VPS4A activity, so retain as non-core. Supporting Evidence: UniProt:Q9UN37 VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan |
| GO:0005515 protein binding | IPI PMID:16730941 A systematic analysis of human CHMP protein interactions: ad... | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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:17110338 Hsp90 cochaperone Aha1 downregulation rescues misfolding of ... | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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:17928862 ESCRT-III recognition by VPS4 ATPases. | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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:24814515 ANCHR mediates Aurora-B-dependent abscission checkpoint cont... | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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:26618866 ∆F508 CFTR interactome remodelling promotes rescue of cystic... | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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:31324722 Inhibition of calpain 1 restores plasma membrane stability t... | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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 evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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:35156780 CFTR interactome mapping using the mammalian membrane two-hy... | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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:36012204 Differential CFTR-Interactome Proximity Labeling Procedures ... | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0036258 multivesicular body assembly | IEA GO_REF:0000107 | ACCEPT | Summary: Supported as part of the core VPS4A endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4A ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| 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 VPS4A 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 VPS4A. Supporting Evidence: PMID:11595185 Dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 and MLV budding. PMID:17940959 A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80% |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Supported localization or pathway context, but not central enough to define VPS4A core function. Reason: Keep as a non-core context attached to the broader ESCRT ATPase role. Supporting Evidence: PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0061738 late endosomal microautophagy | IEA GO_REF:0000107 | UNDECIDED | Summary: Late endosomal microautophagy is a plausible ESCRT-dependent process, but this specific human VPS4A annotation is based on transferred or automated evidence in the local files. Reason: Retain uncertainty pending direct human evidence or a reviewed source tying VPS4A 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:0030496 midbody | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Supported cell-division or midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| GO:0090148 membrane fission | IDA PMID:36604498 Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly ... | ACCEPT | Summary: Supported as part of the ESCRT-III/VPS4 membrane-remodeling machinery. Reason: Recent CHMP2A-CHMP3-VPS4 reconstitution supports VPS4 participation in membrane constriction and cleavage; this is a core ESCRT output. Supporting Evidence: PMID:36604498 VPS4 can constrict and cleave CHMP2A-CHMP3 membrane tubes PMID:36604498 CHMP2A-CHMP3-VPS4 act as a minimal membrane fission machinery. UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. |
| GO:0140545 ATP-dependent protein disaggregase activity | IDA PMID:36604498 Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly ... | ACCEPT | Summary: Core VPS4A function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4A and directly supports ESCRT recycling and downstream membrane remodeling. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. |
| 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 VPS4A 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 VPS4A molecular role. Reason: Keep as a non-core ESCRT membrane-sealing context; VPS4A 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 VPS4A 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 VPS4A. Supporting Evidence: PMID:11595185 Dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 and MLV 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 VPS4A annotation is yeast-only or review-level rather than direct human VPS4A evidence. Reason: The annotation overstates the direct evidence for human VPS4A 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 VPS4A molecular role. Reason: Keep as a non-core ESCRT membrane-sealing context; VPS4A 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 midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| 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 VPS4A molecular role. Reason: Keep as a non-core ESCRT membrane-sealing context; VPS4A 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 VPS4A endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4A ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| 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 VPS4A 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 VPS4A. Supporting Evidence: PMID:11595185 Dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 and MLV 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 VPS4A endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4A ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| 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 midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| 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 VPS4A endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4A ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0090148 membrane fission | NAS PMID:19234443 Membrane scission by the ESCRT-III complex. | ACCEPT | Summary: Supported as part of the ESCRT-III/VPS4 membrane-remodeling machinery. Reason: Recent CHMP2A-CHMP3-VPS4 reconstitution supports VPS4 participation in membrane constriction and cleavage; this is a core ESCRT output. Supporting Evidence: PMID:36604498 VPS4 can constrict and cleave CHMP2A-CHMP3 membrane tubes PMID:36604498 CHMP2A-CHMP3-VPS4 act as a minimal membrane fission machinery. UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 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 VPS4A annotation is yeast-only or review-level rather than direct human VPS4A evidence. Reason: The annotation overstates the direct evidence for human VPS4A 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 VPS4A function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4A and directly supports ESCRT recycling and downstream membrane remodeling. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3159232 | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0005829 cytosol | TAS Reactome:R-HSA-917693 | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9610942 | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9610954 | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668389 | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668415 | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0016887 ATP hydrolysis activity | ISS GO_REF:0000024 | ACCEPT | Summary: Core VPS4A function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4A and directly supports ESCRT recycling and downstream membrane remodeling. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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 that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0061952 midbody abscission | IMP PMID:24814515 ANCHR mediates Aurora-B-dependent abscission checkpoint cont... | KEEP AS NON CORE | Summary: Supported cell-division or midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| GO:0016887 ATP hydrolysis activity | TAS Reactome:R-HSA-9668415 | ACCEPT | Summary: Core VPS4A function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4A and directly supports ESCRT recycling and downstream membrane remodeling. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. |
| GO:0007084 mitotic nuclear membrane reassembly | TAS Reactome:R-HSA-2995410 | KEEP AS NON CORE | Summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4A molecular role. Reason: Keep as a non-core ESCRT membrane-sealing context; VPS4A 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:0005515 protein binding | IPI PMID:18606141 Two distinct modes of ESCRT-III recognition are required for... | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. |
| GO:0000916 actomyosin contractile ring contraction | TAS PMID:28242692 LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope clos... | MODIFY | Summary: The evidence supports cytokinetic abscission rather than the broader or less accurate cell-division term currently used. Reason: VPS4A acts in the ESCRT-mediated abscission stage of cytokinesis, so midbody abscission is the better term. Proposed replacements: midbody abscission Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| GO:0140545 ATP-dependent protein disaggregase activity | NAS PMID:28242692 LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope clos... | ACCEPT | Summary: Core VPS4A function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4A and directly supports ESCRT recycling and downstream membrane remodeling. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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:16174732 Structure and ESCRT-III protein interactions of the MIT doma... | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. |
| 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 VPS4A 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 VPS4A. Supporting Evidence: PMID:11595185 Dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 and MLV budding. PMID:17940959 A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80% |
| GO:0032880 regulation of protein localization | IMP PMID:18005716 Identification of human MVB12 proteins as ESCRT-I subunits t... | KEEP AS NON CORE | Summary: Reviewed as a peripheral or insufficiently specific VPS4A annotation relative to the core ESCRT ATPase role. Reason: The annotation is not central enough to define VPS4A core function, but no direct contradiction was found in the local evidence. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. |
| GO:0010008 endosome membrane | IMP PMID:18606141 Two distinct modes of ESCRT-III recognition are required for... | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0044877 protein-containing complex binding | IPI PMID:18606141 Two distinct modes of ESCRT-III recognition are required for... | ACCEPT | Summary: Core VPS4A function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4A and directly supports ESCRT recycling and downstream membrane remodeling. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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 midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| GO:0006998 nuclear envelope organization | TAS PMID:28242692 LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope clos... | KEEP AS NON CORE | Summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4A molecular role. Reason: Keep as a non-core ESCRT membrane-sealing context; VPS4A 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:0031468 nuclear membrane reassembly | TAS PMID:28242692 LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope clos... | KEEP AS NON CORE | Summary: Supported nuclear-envelope/nucleus-organization ESCRT context, but not the primary VPS4A molecular role. Reason: Keep as a non-core ESCRT membrane-sealing context; VPS4A 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:1904903 ESCRT III complex disassembly | NAS PMID:28242692 LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope clos... | ACCEPT | Summary: Core VPS4A function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4A and directly supports ESCRT recycling and downstream membrane remodeling. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. |
| GO:0006622 protein targeting to lysosome | IMP PMID:16973552 Human ESCRT-II complex and its role in human immunodeficienc... | ACCEPT | Summary: Supported as part of the core VPS4A endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4A ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0044878 mitotic cytokinesis checkpoint signaling | IMP PMID:24814515 ANCHR mediates Aurora-B-dependent abscission checkpoint cont... | KEEP AS NON CORE | Summary: Supported cell-division or midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| GO:0030496 midbody | TAS PMID:28242692 LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope clos... | KEEP AS NON CORE | Summary: Supported cell-division or midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| GO:0061640 cytoskeleton-dependent cytokinesis | TAS PMID:28242692 LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope clos... | KEEP AS NON CORE | Summary: Supported cell-division or midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| 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 VPS4A annotation is yeast-only or review-level rather than direct human VPS4A evidence. Reason: The annotation overstates the direct evidence for human VPS4A 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 VPS4A endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4A ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:1904903 ESCRT III complex disassembly | NAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: Core VPS4A function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4A and directly supports ESCRT recycling and downstream membrane remodeling. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. |
| GO:1904896 ESCRT complex disassembly | NAS PMID:21118109 The role of ESCRT proteins in fusion events involving lysoso... | ACCEPT | Summary: Core VPS4A function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4A and directly supports ESCRT recycling and downstream membrane remodeling. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. |
| GO:0036258 multivesicular body assembly | ISS GO_REF:0000024 | ACCEPT | Summary: Supported as part of the core VPS4A endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4A ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0061738 late endosomal microautophagy | ISS GO_REF:0000024 | UNDECIDED | Summary: Late endosomal microautophagy is a plausible ESCRT-dependent process, but this specific human VPS4A annotation is based on transferred or automated evidence in the local files. Reason: Retain uncertainty pending direct human evidence or a reviewed source tying VPS4A 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:0005524 ATP binding | IMP PMID:10637304 ATPase-defective mammalian VPS4 localizes to aberrant endoso... | ACCEPT | Summary: Accept ATP binding as part of the core AAA ATPase mechanism that enables VPS4A ATP hydrolysis and ESCRT-III remodeling. Reason: ATP binding is a mechanistic prerequisite for the accepted ATP hydrolysis and ATP-dependent protein-disaggregase activity of VPS4A; it is less specific than hydrolysis but consistent with the core ATPase function. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly |
| GO:0005764 lysosome | IDA PMID:10637304 ATPase-defective mammalian VPS4 localizes to aberrant endoso... | KEEP AS NON CORE | Summary: Supported localization or pathway context, but not central enough to define VPS4A core function. Reason: Keep as a non-core context attached to the broader ESCRT ATPase role. Supporting Evidence: PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0005769 early endosome | IDA PMID:10637304 ATPase-defective mammalian VPS4 localizes to aberrant endoso... | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0005770 late endosome | IDA PMID:10637304 ATPase-defective mammalian VPS4 localizes to aberrant endoso... | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0005774 vacuolar membrane | IDA PMID:10637304 ATPase-defective mammalian VPS4 localizes to aberrant endoso... | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0005829 cytosol | IDA PMID:10637304 ATPase-defective mammalian VPS4 localizes to aberrant endoso... | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0016197 endosomal transport | IMP PMID:10637304 ATPase-defective mammalian VPS4 localizes to aberrant endoso... | ACCEPT | Summary: Supported as part of the core VPS4A endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4A ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0016887 ATP hydrolysis activity | IMP PMID:10637304 ATPase-defective mammalian VPS4 localizes to aberrant endoso... | ACCEPT | Summary: Core VPS4A function: ATP-driven recognition, remodeling, and disassembly of ESCRT-III/protein assemblies. Reason: This is the central conserved molecular role of VPS4A and directly supports ESCRT recycling and downstream membrane remodeling. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. |
| GO:0032367 intracellular cholesterol transport | IMP PMID:10637304 ATPase-defective mammalian VPS4 localizes to aberrant endoso... | MODIFY | Summary: ATPase-defective hVPS4 produces cholesterol-enriched endosomal compartments, but VPS4A is not a cholesterol transporter. Reason: The cholesterol phenotype is a consequence of disrupted postendosomal trafficking; endosomal transport better captures the supported role. Proposed replacements: endosomal transport Supporting Evidence: PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| 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 evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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 evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. |
| GO:0034058 endosomal vesicle fusion | IMP PMID:15075231 ATPase-deficient hVPS4 impairs formation of internal endosom... | MODIFY | Summary: The hVPS4(EQ) evidence supports ILV formation and coat disassembly on endosomal vacuoles, not endosomal vesicle fusion. Reason: The biological effect is MVB/ILV biogenesis; fusion is the wrong process for this evidence. Proposed replacements: multivesicular body assembly Supporting Evidence: PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0005737 cytoplasm | IDA PMID:15075231 ATPase-deficient hVPS4 impairs formation of internal endosom... | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0005769 early endosome | IDA PMID:15075231 ATPase-deficient hVPS4 impairs formation of internal endosom... | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0005770 late endosome | IDA PMID:15075231 ATPase-deficient hVPS4 impairs formation of internal endosom... | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0006900 vesicle budding from membrane | IMP PMID:15075231 ATPase-deficient hVPS4 impairs formation of internal endosom... | ACCEPT | Summary: Supported endosomal ILV formation/coat-disassembly role downstream of VPS4A ATPase activity. Reason: ATPase-deficient hVPS4 reduces internal endosomal vesicles and stabilizes coats, consistent with this MVB biogenesis function. Supporting Evidence: PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0072319 vesicle uncoating | IMP PMID:15075231 ATPase-deficient hVPS4 impairs formation of internal endosom... | ACCEPT | Summary: Supported endosomal ILV formation/coat-disassembly role downstream of VPS4A ATPase activity. Reason: ATPase-deficient hVPS4 reduces internal endosomal vesicles and stabilizes coats, consistent with this MVB biogenesis function. Supporting Evidence: PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0005515 protein binding | IPI PMID:18997780 Structural basis for midbody targeting of spastin by the ESC... | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. |
| GO:0019076 viral release from host cell | IMP PMID:11595185 Tsg101 and the vacuolar protein sorting pathway are essentia... | KEEP AS NON CORE | Summary: Directly supported viral/plasma-membrane ESCRT context, but this is host-pathogen exploitation of VPS4A 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 VPS4A. Supporting Evidence: PMID:11595185 Dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 and MLV budding. PMID:17940959 A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80% |
| GO:0005768 endosome | IDA PMID:17940959 Involvement of vacuolar protein sorting pathway in Ebola vir... | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0005886 plasma membrane | IDA 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 VPS4A 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 VPS4A. Supporting Evidence: PMID:11595185 Dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 and MLV budding. PMID:17940959 A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80% |
| GO:0051301 cell division | IDA PMID:17853893 Human ESCRT and ALIX proteins interact with proteins of the ... | MODIFY | Summary: The evidence supports cytokinetic abscission rather than the broader or less accurate cell-division term currently used. Reason: VPS4A acts in the ESCRT-mediated abscission stage of cytokinesis, so midbody abscission is the better term. Proposed replacements: midbody abscission Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| GO:1903076 regulation of protein localization to plasma membrane | IMP PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | KEEP AS NON CORE | Summary: Directly supported viral/plasma-membrane ESCRT context, but this is host-pathogen exploitation of VPS4A 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 VPS4A. Supporting Evidence: PMID:11595185 Dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 and MLV budding. PMID:17940959 A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80% |
| GO:1903774 positive regulation of viral budding via host ESCRT complex | IMP PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | KEEP AS NON CORE | Summary: Directly supported viral/plasma-membrane ESCRT context, but this is host-pathogen exploitation of VPS4A 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 VPS4A. Supporting Evidence: PMID:11595185 Dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 and MLV budding. PMID:17940959 A lack of VPS4 adenosine triphosphatase activity reduced budding by up to 80% |
| 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 midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| 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 VPS4A molecular role. Reason: Keep as a non-core ESCRT membrane-sealing context; VPS4A 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 that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| 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 midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| 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 VPS4A molecular role. Reason: Keep as a non-core ESCRT membrane-sealing context; VPS4A 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: VPS4A/ESCRT depletion can perturb spindle and chromosome phenotypes, but this does not show VPS4A is a metaphase chromosome-alignment factor. Reason: The term overstates a downstream cell-division phenotype relative to the direct ESCRT/VPS4 mechanism. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| 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 midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| 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:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:1903543 positive regulation of exosomal secretion | IMP PMID:22660413 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. | KEEP AS NON CORE | Summary: Supported exosome-release context for VPS4A/B but not the primary cellular function. Reason: Exosome secretion is one downstream ESCRT-dependent output of VPS4A activity, so retain as non-core. Supporting Evidence: UniProt:Q9UN37 VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan |
| 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 VPS4A 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 VPS4A. Supporting Evidence: PMID:11595185 Dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 and MLV 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 | 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 VPS4A endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4A ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| 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 VPS4A localization. Reason: VPS4A 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:Q9UN37 VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan |
| GO:0030496 midbody | IDA PMID:24814515 ANCHR mediates Aurora-B-dependent abscission checkpoint cont... | KEEP AS NON CORE | Summary: Supported cell-division or midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| GO:0032466 negative regulation of cytokinesis | IMP PMID:24814515 ANCHR mediates Aurora-B-dependent abscission checkpoint cont... | KEEP AS NON CORE | Summary: Supported cell-division or midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| GO:0005515 protein binding | IPI PMID:14519844 Divergent retroviral late-budding domains recruit vacuolar p... | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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:14505570 The protein network of HIV budding. | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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:19199708 Proteomic analysis of human parotid gland exosomes by multid... | MARK AS OVER ANNOTATED | Summary: High-throughput exosome proteomics does not establish extracellular exosome as a core VPS4A localization. Reason: VPS4A 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:Q9UN37 VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan |
| GO:0005515 protein binding | IPI PMID:21543490 Mechanism of inhibition of retrovirus release from cells by ... | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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:19129480 Essential role of hIST1 in cytokinesis. | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. |
| GO:0030496 midbody | IDA PMID:19129479 Biochemical analyses of human IST1 and its function in cytok... | KEEP AS NON CORE | Summary: Supported cell-division or midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| 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 evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. |
| GO:0030496 midbody | IDA PMID:17853893 Human ESCRT and ALIX proteins interact with proteins of the ... | KEEP AS NON CORE | Summary: Supported cell-division or midbody/spindle context for VPS4A, downstream of its ESCRT ATPase function. Reason: This is a bona fide VPS4A cellular role but is context-specific and 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:24814515 ANCHR associates with VPS4 at the midbody ring following DNA segregation defects to control abscission timing |
| GO:0016197 endosomal transport | IMP PMID:11559748 CHMP1 functions as a member of a newly defined family of ves... | ACCEPT | Summary: Supported as part of the core VPS4A endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4A ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0005515 protein binding | IPI PMID:11559748 CHMP1 functions as a member of a newly defined family of ves... | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly 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:11563910 Mammalian cells express two VPS4 proteins both of which are ... | MARK AS OVER ANNOTATED | Summary: The underlying interaction evidence may be useful context, especially for ESCRT-III, IST1, ZFYVE19/ANCHR, VPS4B, SPAST, or high-throughput interactome partners, but GO:0005515 is too generic to describe VPS4A molecular function. Reason: VPS4A function is better represented by ATP-dependent ESCRT-III remodeling/disassembly and, where supported, protein-containing complex binding. A generic protein-binding annotation obscures the actual function. Supporting Evidence: file:human/VPS4A/VPS4A-notes.md Plain `GO:0005515 protein binding` rows should not be retained as informative functions. PMID:17928862 VPS4 ATPases perform a key function in this pathway by recognizing membrane-associated ESCRT-III assemblies and catalysing their disassembly PMID:18606141 Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. |
| GO:0005737 cytoplasm | IDA PMID:11563910 Mammalian cells express two VPS4 proteins both of which are ... | ACCEPT | Summary: Supported localization for a cytosolic AAA ATPase that is recruited to endosomal/vacuolar membranes during ESCRT function. Reason: VPS4A cycles between cytosol and membrane-associated ESCRT assemblies; these compartments are consistent with the core endosomal/MVB role. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0016192 vesicle-mediated transport | IDA PMID:11563910 Mammalian cells express two VPS4 proteins both of which are ... | ACCEPT | Summary: Supported as part of the core VPS4A endosomal/MVB sorting and ESCRT-recycling function. Reason: VPS4A ATPase activity recycles ESCRT-III assemblies, enabling MVB sorting, ILV formation, and late endosomal cargo transport. Supporting Evidence: UniProt:Q9UN37 Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly UniProt:Q9UN37 Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:11563910 Mammalian cells express two VPS4 proteins both of which are ... | KEEP AS NON CORE | Summary: Supported localization or pathway context, but not central enough to define VPS4A core function. Reason: Keep as a non-core context attached to the broader ESCRT ATPase role. Supporting Evidence: PMID:10637304 The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking PMID:15075231 hVPS4(EQ) leads to a reduction in the number of internal vesicles in early and late endosomal vacuoles |
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Download this section (compressed HTML)Q: Which ESCRT-dependent cellular contexts require VPS4A specifically rather than VPS4B or mixed VPS4A/VPS4B assemblies?
Q: Is there direct human-cell evidence that VPS4A participates in phagophore closure, late endosomal microautophagy, or another autophagy subtype independent of its generic ESCRT-III disassembly role?
Q: Which disease-associated VPS4A variants selectively perturb ATP hydrolysis, ESCRT-III recognition, hexamer assembly, or recruitment to specific membrane compartments?
Experiment: Use rescue assays after VPS4A/VPS4B double depletion with wild-type, ATPase-dead, and MIT-interface VPS4A mutants across MVB cargo sorting, cytokinesis, nuclear-envelope sealing, and autophagy assays.
Hypothesis: ATPase activity and ESCRT-III recognition are separable requirements whose importance differs by ESCRT-dependent cellular context.
Experiment: Measure endogenous VPS4A recruitment and ESCRT-III turnover during phagophore closure or late endosomal microautophagy with live-cell imaging and acute VPS4A-specific perturbation.
Hypothesis: If VPS4A has a direct autophagy role, it should be transiently recruited to the relevant membrane and required for ESCRT-III turnover there.
Experiment: Biochemically compare VPS4A and VPS4B disassembly of defined human CHMP2A-CHMP3, CHMP4, and mixed ESCRT-III polymers.
Hypothesis: VPS4A has conserved ATP-driven ESCRT-III disassembly activity but may differ from VPS4B in substrate preference or kinetics.
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