CHMP1A (Charged Multivesicular Body Protein 1A) is a member of the SNF7 family and a core subunit of the ESCRT-III complex. CHMP1A functions as a membrane-remodeling protein that mediates topologically equivalent membrane fission events at multiple cellular sites. Its primary roles include: (1) MVB/ILV biogenesis at endosomes where it contributes to receptor downregulation and cargo sorting; (2) cytokinetic abscission at the midbody during the final stages of cell division; (3) nuclear envelope reformation following mitosis; (4) plasma membrane repair; and (5) autophagosome maturation. CHMP1A self-associates and interacts with VPS4A/B ATPases for polymer disassembly, and with other ESCRT-III subunits including CHMP1B and IST1. The protein also has a nuclear function related to chromatin condensation through interaction with the Polycomb group protein BMI1. Biallelic loss-of-function mutations in CHMP1A cause pontocerebellar hypoplasia type 8 (PCH8), linking defective MVB/extracellular vesicle biogenesis to neurodevelopmental pathology.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005771 multivesicular body | IBA GO_REF:0000033 | ACCEPT | Summary: CHMP1A is an established ESCRT-III subunit that localizes to and functions at multivesicular bodies. As a core component of ESCRT-III, it is involved in MVB formation and ILV biogenesis (PMID:17984323, deep research). Reason: Well-supported by phylogenetic analysis and consistent with CHMP1A's established role as an ESCRT-III subunit involved in MVB formation and intraluminal vesicle biogenesis. Supporting Evidence: PMID:17984323 The endosomal sorting complexes required for transport (ESCRTs) are required to sort integral membrane proteins into intralumenal vesicles of the multivesicular body (MVB). file:human/CHMP1A/CHMP1A-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0015031 protein transport | IBA GO_REF:0000033 | ACCEPT | Summary: CHMP1A participates in protein transport as part of the ESCRT-III machinery that sorts cargo into intraluminal vesicles of multivesicular bodies. Reason: Appropriate general term for ESCRT-III function in cargo sorting. CHMP1A as part of ESCRT-III is essential for the transport and sorting of ubiquitinated proteins to lysosomes. Supporting Evidence: PMID:11559748 CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins. |
| GO:0032509 endosome transport via multivesicular body sorting pathway | IBA GO_REF:0000033 | ACCEPT | Summary: CHMP1A is an ESCRT-III component essential for the MVB sorting pathway that mediates cargo transport from endosomes to lysosomes. Reason: Core function annotation. CHMP1A participates in the MVB sorting pathway as part of ESCRT-III, which forms polymeric assemblies that mediate membrane fission for ILV formation. Supporting Evidence: PMID:16554368 this ESCRT subunit, like Tsg101, is important for degradation of the epidermal growth factor (EGF) receptor (EGFR) and for transport of the receptor from early endosomes to lysosomes |
| GO:0045324 late endosome to vacuole transport | IBA GO_REF:0000033 | ACCEPT | Summary: CHMP1A functions in late endosome to lysosome transport as part of the ESCRT-III complex. This is a conserved function across eukaryotes. Reason: Phylogenetically conserved function of ESCRT-III. The mammalian equivalent of vacuolar transport is lysosomal delivery, which requires functional ESCRT-III for MVB-lysosome fusion. Supporting Evidence: PMID:17984323 functional MVBs are also required for efficient clearance of the expanded polyglutamine aggregates |
| GO:0000815 ESCRT III complex | IBA GO_REF:0000033 | ACCEPT | Summary: CHMP1A is a core subunit of the ESCRT-III complex, belonging to the SNF7 family. It self-associates and interacts with other ESCRT-III components. Reason: Definitive membership in ESCRT-III complex. CHMP1A is classified in the SNF7 family and biochemically characterized as an ESCRT-III subunit (UniProt, PMID:14505570, PMID:14519844). Supporting Evidence: PMID:14505570 The protein network of HIV budding PMID:14519844 Divergent retroviral late-budding domains recruit vacuolar protein sorting factors |
| GO:0000776 kinetochore | IEA GO_REF:0000117 | ACCEPT | Summary: ESCRT-III components have been reported at kinetochores. This annotation is supported by experimental evidence from PMID:26040712 showing ESCRT-III localization at spindle-related structures. Reason: IEA annotation consistent with experimental evidence (PMID:26040712). CHMP1A depletion causes mitotic defects including chromosome alignment problems (PMID:20616062). Supporting Evidence: PMID:26040712 Here we show that endosomal sorting complex required for transport (ESCRT)-III, previously found to promote membrane constriction and sealing during receptor sorting, virus budding, cytokinesis and plasma membrane repair, is transiently recruited to the reassembling nuclear envelope during late anaphase |
| GO:0001778 plasma membrane repair | IEA GO_REF:0000117 | ACCEPT | Summary: ESCRT machinery is required for plasma membrane repair. This is a documented ESCRT-III function demonstrated in PMID:24482116. Reason: Well-supported ESCRT-III function. The Science paper demonstrates that ESCRT proteins are recruited within seconds to plasma membrane wounds and mediate repair via extracellular shedding. Supporting Evidence: PMID:24482116 ESCRT machinery is required for plasma membrane repair...ESCRT proteins were recruited within seconds to plasma membrane wounds |
| GO:0005643 nuclear pore | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ESCRT-III is involved in nuclear pore quality control and NPC surveillance, sealing the nuclear envelope at sites where it engulfs structures. Reason: While ESCRT-III localizes near nuclear pores during nuclear envelope reformation and participates in NPC quality control (deep research: Keeley & Coyne 2024), this is not a permanent localization but rather a transient function during mitotic exit. Supporting Evidence: PMID:26040713 Here we show that the endosomal sorting complex required for transport-III (ESCRT-III) machinery localizes to sites of annular fusion in the forming NE in human cells, and is necessary for proper post-mitotic nucleo-cytoplasmic compartmentalization |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: CHMP1A has cytoplasmic localization as documented in UniProt annotations. Reason: Basic localization annotation consistent with UniProt subcellular location data. The cytoplasmic form is partially membrane-associated (UniProt). Supporting Evidence: PMID:11559748 CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000117 | ACCEPT | Summary: ESCRT-III components localize to lysosomal membranes in the context of autophagosome-lysosome fusion and MVB-lysosome fusion. Reason: Consistent with ESCRT-III function in autophagy and endolysosomal trafficking. Experimental evidence from PMID:17984323 supports this localization. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance |
| GO:0005828 kinetochore microtubule | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ESCRT-III has roles at spindle microtubules. CHMP1A depletion affects spindle organization (PMID:20616062). Reason: While ESCRT-III/VPS4 proteins function at spindles and their depletion affects mitotic spindle organization, the direct localization to kinetochore microtubules is less well characterized for CHMP1A specifically compared to other ESCRT-III subunits. Supporting Evidence: PMID:20616062 depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers, producing multipolar spindles |
| GO:0006351 DNA-templated transcription | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: CHMP1A was originally characterized as having chromatin-modifying activity and affecting gene expression through interaction with Polycomb group proteins. Reason: The nuclear function of CHMP1A in transcriptional regulation through PcG protein BMI1 is documented (PMID:11559747) but is secondary to its primary ESCRT-III membrane fission functions. Supporting Evidence: PMID:11559747 CHMP1 can recruit a PcG protein, BMI1, to these regions of condensed chromatin |
| GO:0007034 vacuolar transport | IEA GO_REF:0000002 | ACCEPT | Summary: CHMP1A is involved in vacuolar/lysosomal transport as an ESCRT-III subunit. The Snf7 domain (IPR005024) is characteristic of proteins involved in MVB sorting. Reason: InterPro-based annotation consistent with CHMP1A's role as an ESCRT-III/Snf7 family member involved in endolysosomal trafficking. |
| GO:0007080 mitotic metaphase chromosome alignment | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ESCRT-III depletion causes chromosome alignment defects. This is experimentally demonstrated for CHMP1A (PMID:20616062). Reason: While CHMP1A depletion affects chromosome alignment, this is a secondary consequence of centrosome/spindle dysfunction rather than a direct function in alignment. Supporting Evidence: PMID:20616062 causing defects in chromosome segregation and nuclear morphology |
| GO:0010008 endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: CHMP1A localizes to endosomal membranes as part of ESCRT-III function in MVB formation. Reason: Core localization for ESCRT-III function. UniProt documents endosome membrane association. Supporting Evidence: PMID:11559748 Immunocytochemistry and biochemical fractionation localize CHMP1 to early endosomes |
| GO:0015031 protein transport | IEA GO_REF:0000043 | ACCEPT | Summary: CHMP1A functions in protein transport as an ESCRT-III component involved in cargo sorting. Reason: Duplicate of IBA annotation with same GO term. Both are valid; this IEA is from UniProtKB keyword mapping and is consistent with the phylogenetically-inferred annotation. |
| GO:0016363 nuclear matrix | IEA GO_REF:0000044 | ACCEPT | Summary: CHMP1A has a nuclear form that associates with the nuclear matrix, documented experimentally. Reason: Experimentally validated localization (PMID:11559747). The nuclear form of CHMP1A remains associated with the chromosome scaffold during mitosis. Supporting Evidence: PMID:11559747 CHMP1 contains a predicted bipartite nuclear localization signal and distributes as distinct forms to the cytoplasm and the nuclear matrix in all cell lines tested |
| GO:0030496 midbody | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP1A localizes to the midbody during cytokinesis as part of the ESCRT-III abscission machinery. Reason: Core localization for cytokinetic function. ESCRT-III is recruited to the midbody for abscission (PMID:20616062, PMID:26040712). Supporting Evidence: PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis |
| GO:0031468 nuclear membrane reassembly | IEA GO_REF:0000117 | ACCEPT | Summary: ESCRT-III is required for nuclear envelope reformation after mitosis. Two Nature papers in 2015 established this function. Reason: Well-documented ESCRT-III function. PMID:26040712 and PMID:26040713 demonstrate ESCRT-III role in sealing the nuclear envelope during telophase. Supporting Evidence: PMID:26040713 Here we show that the endosomal sorting complex required for transport-III (ESCRT-III) machinery localizes to sites of annular fusion in the forming NE in human cells, and is necessary for proper post-mitotic nucleo-cytoplasmic compartmentalization |
| GO:0032585 multivesicular body membrane | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP1A localizes to MVB membranes as part of ESCRT-III function in ILV formation. Reason: Core localization. Experimentally supported by PMID:16554368. Supporting Evidence: PMID:16554368 this ESCRT subunit, like Tsg101, is important for degradation of the epidermal growth factor (EGF) receptor (EGFR) and for transport of the receptor from early endosomes to lysosomes |
| GO:0039702 viral budding via host ESCRT complex | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ESCRT-III is hijacked by enveloped viruses including HIV for budding. CHMP1A is part of this machinery. Reason: This is a documented ESCRT-III function in viral budding (PMID:14505570, PMID:24878737), but represents viral exploitation of the cellular machinery rather than an endogenous core function. Supporting Evidence: PMID:14505570 The protein network of HIV budding |
| GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | IEA GO_REF:0000117 | ACCEPT | Summary: ESCRT-III sorts ubiquitinated cargo into ILVs for lysosomal degradation. Reason: Core function of the ESCRT pathway. Ubiquitinated proteins are sorted into MVBs and delivered to lysosomes for degradation (PMID:17984323). Supporting Evidence: PMID:17984323 leading to accumulation of protein aggregates containing ubiquitinated proteins |
| GO:0046761 viral budding from plasma membrane | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ESCRT-III is used by viruses for budding from the plasma membrane. Reason: Documented ESCRT-III function in viral budding (PMID:24878737), but represents viral exploitation rather than an endogenous function. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding |
| GO:0051301 cell division | IEA GO_REF:0000043 | ACCEPT | Summary: CHMP1A functions in cell division through its role in cytokinetic abscission and centrosome maintenance. Reason: Well-supported by experimental evidence (PMID:20616062, PMID:19129479). ESCRT-III depletion blocks abscission. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission |
| GO:0061952 midbody abscission | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP1A is required for cytokinetic abscission at the midbody. Reason: Core function. ESCRT-III mediates the final membrane fission step of cytokinesis. Depletion of CHMP1A impairs abscission (PMID:20616062, deep research). Supporting Evidence: PMID:20616062 The ESCRT pathway helps mediate the final abscission step of cytokinesis |
| GO:0071985 multivesicular body sorting pathway | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP1A is an ESCRT-III subunit essential for the MVB sorting pathway. Reason: Core function. CHMP1A as part of ESCRT-III is required for MVB formation and cargo sorting (PMID:16554368). Supporting Evidence: PMID:16554368 this ESCRT subunit, like Tsg101, is important for degradation of the epidermal growth factor (EGF) receptor (EGFR) and for transport of the receptor from early endosomes to lysosomes |
| GO:0097352 autophagosome maturation | IEA GO_REF:0000117 | ACCEPT | Summary: ESCRT-III is required for autophagosome maturation and fusion with lysosomes. Reason: Functional MVBs are required for autophagy (PMID:17984323). ESCRT depletion causes accumulation of protein aggregates due to impaired autophagic degradation. Supporting Evidence: PMID:17984323 autophagic degradation is inhibited in cells depleted of ESCRT subunits |
| GO:1901673 regulation of mitotic spindle assembly | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ESCRT-III/VPS4 depletion affects spindle assembly and centrosome numbers. Reason: While ESCRT-III depletion causes spindle defects (PMID:20616062), the mechanistic role is likely indirect through centrosome maintenance rather than direct regulation of spindle assembly. Supporting Evidence: PMID:20616062 depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers |
| GO:1902774 late endosome to lysosome transport | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP1A functions in late endosome to lysosome transport as part of ESCRT-III. Reason: Core endolysosomal trafficking function. MVBs fuse with lysosomes to deliver cargo for degradation (PMID:17984323, PMID:16505166). Supporting Evidence: PMID:17984323 functional MVBs are required for clearance of TDP-43 |
| GO:1904930 amphisome membrane | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP1A localizes to amphisome membranes, structures formed by autophagosome-endosome fusion. Reason: Consistent with ESCRT-III function in autophagy and the requirement for functional MVBs in autophagic clearance (PMID:17984323). |
| GO:0005515 protein binding | IPI PMID:16730941 A systematic analysis of human CHMP protein interactions; ad... | MARK AS OVER ANNOTATED | Summary: CHMP1A binds multiple ESCRT-related proteins including STAMBP, CHMP1B, and VPS4A. Reason: Generic protein binding is not informative. The specific interactions documented in this paper (ESCRT-III components, MIT domain proteins) are more informative. Consider more specific terms like ESCRT complex binding. Supporting Evidence: PMID:16730941 May 30. A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex. |
| GO:0005515 protein binding | IPI PMID:17711858 The MIT domain of UBPY constitutes a CHMP binding and endoso... | MARK AS OVER ANNOTATED | Summary: Documents UBPY (USP8) and STAMBP interactions with CHMP1A via MIT domains. Reason: Generic protein binding. The paper documents specific interactions with deubiquitinating enzymes via MIT domain recognition of CHMP1A. Supporting Evidence: PMID:17711858 2007 Aug 21. The MIT domain of UBPY constitutes a CHMP binding and endosomal localization signal required for efficient epidermal growth factor receptor degradation. |
| GO:0005515 protein binding | IPI PMID:19302785 Ab initio protein modelling reveals novel human MIT domains. | MARK AS OVER ANNOTATED | Summary: Ab initio modeling identifies MIT domain proteins that interact with CHMP1A. Reason: Generic protein binding annotation from a structural modeling study. More specific molecular function terms would be more informative. Supporting Evidence: PMID:19302785 2009 Feb 12. Ab initio protein modelling reveals novel human MIT domains. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | MARK AS OVER ANNOTATED | Summary: High-throughput interactome study identifying CHMP1A interactions. Reason: Generic protein binding from a large-scale study. Not informative about specific molecular function. Supporting Evidence: PMID:21988832 Toward an understanding of the protein interaction network of the human liver. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Large-scale interactome mapping study. Reason: Generic protein binding annotation from high-throughput study. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Reference map of human binary protein interactome identifies CHMP1A interactions. Reason: Generic protein binding from systematic interactome study. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Interactome study of neurodegenerative disease proteins identifies CHMP1A interactions with huntingtin (HTT), alpha-synuclein (SNCA). Reason: Generic protein binding. The interactions with disease proteins are interesting but the generic term is not informative. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Dual proteome-scale network study. Reason: Generic protein binding from high-throughput study. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell Endogenous tagging for the cartography of human cel... | MARK AS OVER ANNOTATED | Summary: OpenCell endogenous tagging study. Reason: Generic protein binding annotation. Supporting Evidence: PMID:35271311 2022 Mar 11. OpenCell: Endogenous tagging for the cartography of human cellular organization. |
| GO:0042802 identical protein binding | IPI PMID:16730941 A systematic analysis of human CHMP protein interactions; ad... | ACCEPT | Summary: CHMP1A self-associates to form polymeric assemblies characteristic of ESCRT-III. Reason: ESCRT-III proteins self-associate to form membrane-remodeling polymers. This is a functionally important activity (PMID:16730941, UniProt). Supporting Evidence: PMID:14519844 In particular, interactions between ESCRT-I and ESCRT-III are bridged by AIP-1/ALIX PMID:16730941 May 30. A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex. |
| GO:0042802 identical protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | ACCEPT | Summary: Confirmation of CHMP1A self-association in systematic interactome study. Reason: Duplicate evidence for self-association, which is functionally important for ESCRT-III polymer formation. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence data shows CHMP1A in nucleoplasm. Reason: Consistent with CHMP1A having both cytoplasmic and nuclear forms (PMID:11559747). |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: HPA data shows cytosolic localization. Reason: Consistent with UniProt annotation. ESCRT-III proteins cycle between cytosolic and membrane-associated states. |
| GO:0000421 autophagosome membrane | IDA PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: ESCRT-III localizes to autophagosome membranes where functional MVBs are required for autophagic clearance. Reason: Experimentally demonstrated localization relevant to ESCRT-III function in autophagy. Supporting Evidence: PMID:17984323 autophagic degradation is inhibited in cells depleted of ESCRT subunits |
| GO:0000776 kinetochore | IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly... | KEEP AS NON CORE | Summary: ESCRT-III localizes to kinetochore regions during mitosis as demonstrated by imaging in this study. Reason: While the localization is experimentally demonstrated, the functional significance of ESCRT-III at kinetochores is not fully characterized. Supporting Evidence: PMID:20616062 CHMP3 and CHMP4, were recently reported to localize to kinetochores in a global screen for proteins with possible mitotic functions PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing. |
| GO:0001778 plasma membrane repair | IDA PMID:24482116 ESCRT machinery is required for plasma membrane repair. | ACCEPT | Summary: ESCRT machinery is rapidly recruited to plasma membrane wounds and is required for repair. Reason: Well-documented ESCRT-III function demonstrated with direct experimental evidence. Supporting Evidence: PMID:24482116 ESCRT proteins were recruited within seconds to plasma membrane wounds...repair of certain wounds is ensured by ESCRT-mediated extracellular shedding |
| GO:0005765 lysosomal membrane | IDA PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: ESCRT-III localizes to lysosomal membranes in the context of autophagosome-lysosome fusion. Reason: Experimentally demonstrated localization consistent with ESCRT-III role in autophagy and endolysosomal trafficking. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. |
| GO:0005828 kinetochore microtubule | IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly... | KEEP AS NON CORE | Summary: ESCRT-III localizes to spindle structures during mitosis. Reason: Localization demonstrated but the direct functional role at kinetochore microtubules is not fully characterized for CHMP1A. Supporting Evidence: PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing. |
| GO:0005886 plasma membrane | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: ESCRT-III spirals form at the plasma membrane during viral budding studies. Reason: Experimentally demonstrated localization. ESCRT-III functions at the plasma membrane for viral budding and membrane repair. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding |
| GO:0006914 autophagy | IMP PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: ESCRT depletion inhibits autophagic degradation, causing accumulation of protein aggregates. Reason: Well-documented requirement for functional MVBs in autophagy. Supporting Evidence: PMID:17984323 autophagic degradation is inhibited in cells depleted of ESCRT subunits |
| GO:0006997 nucleus organization | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | KEEP AS NON CORE | Summary: ESCRT-III depletion causes defects in nuclear morphology. Reason: Nuclear defects are observed upon ESCRT-III depletion but this may be secondary to other mitotic defects rather than a direct nuclear organization role. Supporting Evidence: PMID:20616062 causing defects in chromosome segregation and nuclear morphology |
| GO:0007080 mitotic metaphase chromosome alignment | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | KEEP AS NON CORE | Summary: ESCRT-III depletion causes chromosome alignment defects. Reason: Chromosome alignment defects are likely secondary to spindle/centrosome dysfunction rather than a direct role in alignment. Supporting Evidence: PMID:20616062 causing defects in chromosome segregation |
| GO:0030496 midbody | IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly... | ACCEPT | Summary: CHMP1A localizes to the midbody during cytokinesis. Reason: Core localization for cytokinetic function. ESCRT-III is recruited to the midbody for abscission. Supporting Evidence: PMID:20616062 VPS4 proteins concentrated...at midbodies during cytokinesis PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing. |
| GO:0031468 nuclear membrane reassembly | IMP PMID:26040713 ESCRT-III controls nuclear envelope reformation. | ACCEPT | Summary: ESCRT-III is required for sealing the nuclear envelope during telophase. Reason: Core function demonstrated by functional studies. ESCRT-III mediates annular fusion to seal the reforming nuclear envelope. Supporting Evidence: PMID:26040713 Here we show that the endosomal sorting complex required for transport-III (ESCRT-III) machinery localizes to sites of annular fusion in the forming NE in human cells, and is necessary for proper post-mitotic nucleo-cytoplasmic compartmentalization |
| GO:0032585 multivesicular body membrane | IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but... | ACCEPT | Summary: ESCRT-III localizes to MVB membranes for ILV formation. Reason: Core localization for ESCRT-III function in MVB biogenesis. Supporting Evidence: PMID:16554368 this ESCRT subunit, like Tsg101, is important for degradation of the epidermal growth factor (EGF) receptor (EGFR) and for transport of the receptor from early endosomes to lysosomes |
| GO:0036258 multivesicular body assembly | NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a... | ACCEPT | Summary: CHMP1A participates in MVB assembly as an ESCRT-III subunit. Reason: Core function. ESCRT-III is required for MVB assembly and ILV formation. Supporting Evidence: PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1 |
| GO:0039702 viral budding via host ESCRT complex | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | KEEP AS NON CORE | Summary: ESCRT-III spirals form during HIV budding as visualized in this structural study. Reason: Documented ESCRT-III function but represents viral exploitation rather than endogenous function. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding |
| GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | IDA PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: ESCRT is required for degradation of ubiquitinated proteins via the MVB pathway. Reason: Core ESCRT pathway function in targeting ubiquitinated proteins for lysosomal degradation. Supporting Evidence: PMID:17984323 leading to accumulation of protein aggregates containing ubiquitinated proteins |
| GO:0046761 viral budding from plasma membrane | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | KEEP AS NON CORE | Summary: ESCRT-III forms spirals at the plasma membrane during HIV budding. Reason: Documented ESCRT-III function in viral budding but represents viral exploitation of cellular machinery. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding. |
| GO:0051469 vesicle fusion with vacuole | NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a... | KEEP AS NON CORE | Summary: ESCRT-III participates in MVB-lysosome fusion pathway. Reason: While ESCRTs are involved in the MVB pathway, the direct role in fusion (as opposed to MVB formation) is less well characterized. Supporting Evidence: PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1. |
| GO:0061763 multivesicular body-lysosome fusion | NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a... | KEEP AS NON CORE | Summary: ESCRT function is required for MVB-lysosome fusion pathway. Reason: The primary ESCRT-III role is in MVB formation rather than the fusion step, which involves SNARE machinery. Supporting Evidence: PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1. |
| GO:0061952 midbody abscission | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | ACCEPT | Summary: ESCRT-III depletion inhibits cytokinetic abscission. Reason: Core function. ESCRT-III mediates the final membrane fission step of cytokinesis. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission |
| GO:0071985 multivesicular body sorting pathway | IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but... | ACCEPT | Summary: CHMP1A functions in the MVB sorting pathway as an ESCRT-III subunit. Reason: Core function. ESCRT-III is essential for the MVB sorting pathway. Supporting Evidence: PMID:16554368 this ESCRT subunit, like Tsg101, is important for degradation of the epidermal growth factor (EGF) receptor (EGFR) |
| GO:0090148 membrane fission | NAS PMID:19234443 Membrane scission by the ESCRT-III complex. | ACCEPT | Summary: ESCRT-III mediates membrane scission at MVBs, midbody, and other sites. Reason: Core molecular function of ESCRT-III. The complex mediates topologically equivalent membrane fission events. Supporting Evidence: PMID:19234443 Membrane scission by the ESCRT-III complex |
| GO:0097352 autophagosome maturation | IMP PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: Functional MVBs are required for autophagosome maturation and autophagic clearance. Reason: Experimentally demonstrated. ESCRT depletion causes accumulation of protein aggregates. Supporting Evidence: PMID:17984323 autophagic degradation is inhibited in cells depleted of ESCRT subunits |
| GO:1901673 regulation of mitotic spindle assembly | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | KEEP AS NON CORE | Summary: ESCRT-III depletion affects spindle organization. Reason: Spindle defects likely result from centrosome dysfunction rather than direct regulation of spindle assembly. Supporting Evidence: PMID:20616062 depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers |
| GO:1902774 late endosome to lysosome transport | IMP PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: ESCRT is required for efficient transport from late endosomes to lysosomes. Reason: Core endolysosomal trafficking function demonstrated by functional studies. Supporting Evidence: PMID:17984323 functional MVBs are required for clearance |
| GO:1904930 amphisome membrane | IDA PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: ESCRT-III localizes to amphisome membranes. Reason: Consistent with ESCRT-III function in autophagy. Amphisomes are intermediates in autophagosome-lysosome fusion. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. |
| GO:0007076 mitotic chromosome condensation | IDA PMID:11559747 CHMP1 is a novel nuclear matrix protein affecting chromatin ... | KEEP AS NON CORE | Summary: CHMP1A was originally characterized as affecting chromatin condensation. Overexpressed CHMP1A localizes to condensed chromatin. Reason: While documented in the original characterization paper, this appears to be a secondary nuclear function. The IDA evidence is based on overexpression. Supporting Evidence: PMID:11559747 Overexpressed CHMP1 localizes to a punctate subnuclear pattern, encapsulating regions of nuclease-resistant, condensed chromatin |
| GO:0010629 negative regulation of gene expression | IDA PMID:11559747 CHMP1 is a novel nuclear matrix protein affecting chromatin ... | KEEP AS NON CORE | Summary: CHMP1A recruits BMI1 and affects gene silencing through Polycomb group interaction. Reason: Secondary nuclear function. The PcG interaction is documented but is not the primary ESCRT-III membrane fission function. Supporting Evidence: PMID:11559747 CHMP1 can recruit a PcG protein, BMI1, to these regions of condensed chromatin...consistent with a role in PcG function |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9610942 | ACCEPT | Summary: Reactome annotation for HCMV final envelopment complex formation. Reason: Cytosolic localization is consistent with ESCRT-III biology. The soluble pool is recruited to membranes upon activation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9610954 | ACCEPT | Summary: Reactome annotation for HCMV final envelopment. Reason: Duplicate cytosol annotation from Reactome pathway. |
| GO:0036258 multivesicular body assembly | NAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: Review article on ESCRT-mediated membrane budding and scission. Reason: Core function of ESCRT-III in MVB assembly is well established. Supporting Evidence: PMID:20588296 Membrane budding and scission by the ESCRT machinery |
| GO:0039702 viral budding via host ESCRT complex | NAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | KEEP AS NON CORE | Summary: Review discusses ESCRT role in viral budding. Reason: Viral budding is a documented ESCRT function but represents exploitation of cellular machinery. Supporting Evidence: PMID:20588296 Jun 30. Membrane budding and scission by the ESCRT machinery: it's all in the neck. |
| GO:1904903 ESCRT III complex disassembly | NAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: VPS4 disassembles ESCRT-III polymers. CHMP1A participates in this cycle. Reason: VPS4-mediated disassembly is essential for ESCRT-III recycling and function. Supporting Evidence: PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 PMID:20588296 Jun 30. Membrane budding and scission by the ESCRT machinery: it's all in the neck. |
| GO:0051301 cell division | IMP PMID:19129479 Biochemical analyses of human IST1 and its function in cytok... | ACCEPT | Summary: IST1 functional studies demonstrate requirement for ESCRT-III in cell division. Reason: Core function. ESCRT-III is required for cytokinetic abscission. Supporting Evidence: PMID:19129479 Biochemical analyses of human IST1 and its function in cytokinesis |
| GO:0010824 regulation of centrosome duplication | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | KEEP AS NON CORE | Summary: ESCRT-III depletion causes centrosome amplification. Reason: Centrosome defects are observed but the mechanistic role is not fully understood. May involve indirect effects through endosomal trafficking. Supporting Evidence: PMID:20616062 approximately 80% of HeLa cells lacking VPS4B exhibited multiple centrosomes |
| GO:0005515 protein binding | IPI PMID:14519844 Divergent retroviral late-budding domains recruit vacuolar p... | MARK AS OVER ANNOTATED | Summary: Documents CHMP1A interactions with CHMP1B and VPS4A in the context of retroviral budding. Reason: Generic protein binding. The specific interactions documented are more informative than this generic term. Supporting Evidence: PMID:14519844 Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins. |
| GO:0042803 protein homodimerization activity | IPI PMID:14519844 Divergent retroviral late-budding domains recruit vacuolar p... | ACCEPT | Summary: CHMP1A self-associates. Reason: Self-association is important for ESCRT-III polymer formation. Supporting Evidence: PMID:14519844 Divergent retroviral late-budding domains recruit vacuolar protein sorting factors |
| GO:0005515 protein binding | IPI PMID:14505570 The protein network of HIV budding. | MARK AS OVER ANNOTATED | Summary: HIV budding protein network study documenting ESCRT interactions. Reason: Generic protein binding. Specific interactions with VPS4A, VPS4B, CHMP1B are more informative. Supporting Evidence: PMID:14505570 The protein network of HIV budding. |
| GO:0042803 protein homodimerization activity | IPI PMID:14505570 The protein network of HIV budding. | ACCEPT | Summary: CHMP1A self-association documented. Reason: Functionally important self-association for polymer formation. Supporting Evidence: PMID:14505570 The protein network of HIV budding. |
| GO:0005515 protein binding | IPI PMID:23045692 ESCRT-III binding protein MITD1 is involved in cytokinesis a... | MARK AS OVER ANNOTATED | Summary: Documents CHMP1A interaction with MITD1 via C-terminal motif. Reason: Generic protein binding. The specific interaction with MITD1 for cytokinesis is more informative. Supporting Evidence: PMID:23045692 ESCRT-III binding protein MITD1 is involved in cytokinesis and has an unanticipated PLD fold that binds membranes. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: CHMP1A identified in urinary exosome proteomics. Reason: Detection in exosomes may reflect ESCRT-III role in MVB/exosome biogenesis or could be incidental. Not a core localization. Supporting Evidence: PMID:19056867 2008 Dec 3. Large-scale proteomics and phosphoproteomics of urinary exosomes. |
| GO:0005515 protein binding | IPI PMID:19129480 Essential role of hIST1 in cytokinesis. | MARK AS OVER ANNOTATED | Summary: IST1 binds CHMP1A for cytokinesis function. Reason: Generic protein binding. The specific IST1 interaction is documented in the protein domain specific binding annotation. Supporting Evidence: PMID:19129480 Jan 7. Essential role of hIST1 in cytokinesis. |
| GO:0005515 protein binding | IPI PMID:19129479 Biochemical analyses of human IST1 and its function in cytok... | MARK AS OVER ANNOTATED | Summary: Biochemical study of IST1-CHMP1A interaction. Reason: Generic protein binding. Supporting Evidence: PMID:19129479 Jan 7. Biochemical analyses of human IST1 and its function in cytokinesis. |
| GO:0019904 protein domain specific binding | IPI PMID:17928862 ESCRT-III recognition by VPS4 ATPases. | ACCEPT | Summary: CHMP1A C-terminal MIM motif binds VPS4 MIT domain. Structural characterization of the interaction. Reason: Specific and functionally important interaction. The VPS4 MIT domain recognizes ESCRT-III MIM motifs for complex disassembly. Supporting Evidence: PMID:17928862 ESCRT-III recognition by VPS4 ATPases |
| GO:0008237 metallopeptidase activity | TAS PMID:8863740 Molecular cloning, expression and chromosomal localization o... | REMOVE | Summary: This annotation is erroneous. The original 1996 paper incorrectly translated the PRSM1 ORF and proposed metallopeptidase function based on a spurious zinc metalloprotease motif. Reason: UniProt explicitly notes this was "based on a wrong translation of the ORF which gave rise to a putative protein of 318 AA containing a pattern reminiscent of zinc metalloproteases." CHMP1A has no metallopeptidase activity. Supporting Evidence: PMID:8863740 Molecular cloning, expression and chromosomal localization of a human gene encoding a 33 kDa putative metallopeptidase (PRSM1). |
| GO:0008270 zinc ion binding | TAS PMID:8863740 Molecular cloning, expression and chromosomal localization o... | REMOVE | Summary: This annotation is erroneous, arising from the same mistranslation that led to the incorrect metallopeptidase annotation. Reason: Based on erroneous translation of the gene. There is no evidence that CHMP1A binds zinc. UniProt documents this error. Supporting Evidence: PMID:8863740 Molecular cloning, expression and chromosomal localization of a human gene encoding a 33 kDa putative metallopeptidase (PRSM1). |
| GO:0005515 protein binding | IPI PMID:11559748 CHMP1 functions as a member of a newly defined family of ves... | MARK AS OVER ANNOTATED | Summary: Original CHMP1 characterization documenting VPS4A interaction. Reason: Generic protein binding. The VPS4A interaction is captured in more specific annotations. Supporting Evidence: PMID:11559748 CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins. |
| GO:0005515 protein binding | IPI PMID:12445808 Physical interaction between hepatitis C virus NS4B protein ... | MARK AS OVER ANNOTATED | Summary: Hepatitis C virus NS4B interaction with CHMP1A identified. Reason: Generic protein binding from virus-host interaction study. The biological significance is unclear. Supporting Evidence: PMID:12445808 Physical interaction between hepatitis C virus NS4B protein and CREB-RP/ATF6beta. |
| GO:0000794 condensed nuclear chromosome | IDA PMID:11559747 CHMP1 is a novel nuclear matrix protein affecting chromatin ... | KEEP AS NON CORE | Summary: CHMP1A localizes to condensed chromatin upon overexpression. Reason: Secondary nuclear function documented in the original characterization. Overexpression study, may not reflect physiological localization. Supporting Evidence: PMID:11559747 Overexpressed CHMP1 localizes to a punctate subnuclear pattern, encapsulating regions of nuclease-resistant, condensed chromatin |
| GO:0005769 early endosome | IDA PMID:11559748 CHMP1 functions as a member of a newly defined family of ves... | ACCEPT | Summary: CHMP1A localizes to early endosomes. Reason: Consistent with ESCRT-III recruitment to endosomes. The cytoplasmic form is partially membrane-associated and localizes to early endosomes. Supporting Evidence: PMID:11559748 CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins |
| GO:0005815 microtubule organizing center | IDA PMID:11559748 CHMP1 functions as a member of a newly defined family of ves... | KEEP AS NON CORE | Summary: CHMP1A localizes to MTOC/centrosome. Reason: Centrosomal localization is documented and ESCRT-III depletion affects centrosome numbers (PMID:20616062), but the functional role at centrosomes is not fully characterized. Supporting Evidence: PMID:20616062 depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers PMID:11559748 CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins. |
| GO:0012505 endomembrane system | IDA PMID:11559748 CHMP1 functions as a member of a newly defined family of ves... | ACCEPT | Summary: CHMP1A is part of the endomembrane system as an ESCRT-III component. Reason: Appropriate general localization for an ESCRT-III protein that functions at endosomes and other membrane compartments. Supporting Evidence: PMID:11559748 CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins. |
| GO:0016192 vesicle-mediated transport | IDA PMID:11559748 CHMP1 functions as a member of a newly defined family of ves... | ACCEPT | Summary: CHMP1A functions in vesicle trafficking as an ESCRT-III component. Reason: Core function. ESCRT-III mediates vesicle formation at MVBs. Supporting Evidence: PMID:11559748 CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins |
| GO:0016363 nuclear matrix | IDA PMID:11559747 CHMP1 is a novel nuclear matrix protein affecting chromatin ... | ACCEPT | Summary: CHMP1A has a nuclear form that associates with the nuclear matrix. Reason: Experimentally validated localization. CHMP1 distributes to both cytoplasm and nuclear matrix. Supporting Evidence: PMID:11559747 CHMP1 contains a predicted bipartite nuclear localization signal and distributes as distinct forms to the cytoplasm and the nuclear matrix in all cell lines tested |
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Download this section (compressed HTML)Q: What is the specific contribution of CHMP1A vs CHMP1B to ESCRT-III function at different cellular sites?
Suggested experts: Stenmark H
Q: How is CHMP1A recruitment specifically regulated at the nuclear envelope vs midbody vs MVBs?
Suggested experts: Stenmark H, Saksena S
Q: What is the mechanistic basis for the centrosome phenotypes observed upon ESCRT-III depletion?
Suggested experts: Bhutta MS
Experiment: Rescue experiments in CHMP1A-depleted cells to determine which domains are required for different functions
Hypothesis: Different domains of CHMP1A may be differentially required for MVB, cytokinesis, and nuclear envelope functions
Type: Rescue assay
Experiment: Live imaging of endogenously tagged CHMP1A to characterize recruitment dynamics at different cellular sites
Hypothesis: CHMP1A recruitment kinetics differ between MVBs, midbody, and nuclear envelope
Type: Live cell imaging
Experiment: Proximity labeling (BioID/APEX) to identify site-specific CHMP1A interaction partners
Hypothesis: CHMP1A interacts with different proteins at different cellular locations
Type: Proximity proteomics
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