CHMP1A

---
id: Q9HD42
gene_symbol: CHMP1A
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
existing_annotations:
# IBA annotations - phylogenetically informed, generally reliable
  - term:
      id: GO:0005771
      label: multivesicular body
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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).
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: The endosomal sorting complexes required for transport
            (ESCRTs) are required to sort integral membrane proteins into intralumenal
            vesicles of the multivesicular body (MVB).
        - reference_id: file:human/CHMP1A/CHMP1A-deep-research-falcon.md
          supporting_text: 'model: Edison Scientific Literature'
  - term:
      id: GO:0015031
      label: protein transport
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        CHMP1A participates in protein transport as part of the ESCRT-III machinery
        that sorts cargo
        into intraluminal vesicles of multivesicular bodies.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:11559748
          supporting_text: CHMP1 functions as a member of a newly defined family of
            vesicle trafficking proteins.
  - term:
      id: GO:0032509
      label: endosome transport via multivesicular body sorting pathway
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        CHMP1A is an ESCRT-III component essential for the MVB sorting pathway that
        mediates cargo transport
        from endosomes to lysosomes.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:16554368
          supporting_text: 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
  - term:
      id: GO:0045324
      label: late endosome to vacuole transport
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        CHMP1A functions in late endosome to lysosome transport as part of the ESCRT-III
        complex.
        This is a conserved function across eukaryotes.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: functional MVBs are also required for efficient clearance
            of the expanded polyglutamine aggregates
  - term:
      id: GO:0000815
      label: ESCRT III complex
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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).
      supported_by:
        - reference_id: PMID:14505570
          supporting_text: The protein network of HIV budding
        - reference_id: PMID:14519844
          supporting_text: Divergent retroviral late-budding domains recruit vacuolar
            protein sorting factors

# IEA annotations - evaluate against established functions
  - term:
      id: GO:0000776
      label: kinetochore
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      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.
      action: ACCEPT
      reason: >-
        IEA annotation consistent with experimental evidence (PMID:26040712). CHMP1A
        depletion causes
        mitotic defects including chromosome alignment problems (PMID:20616062).
      supported_by:
        - reference_id: PMID:26040712
          supporting_text: 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
  - term:
      id: GO:0001778
      label: plasma membrane repair
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ESCRT machinery is required for plasma membrane repair. This is a documented
        ESCRT-III function
        demonstrated in PMID:24482116.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:24482116
          supporting_text: ESCRT machinery is required for plasma membrane repair...ESCRT
            proteins were recruited within seconds to plasma membrane wounds
  - term:
      id: GO:0005643
      label: nuclear pore
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ESCRT-III is involved in nuclear pore quality control and NPC surveillance,
        sealing
        the nuclear envelope at sites where it engulfs structures.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:26040713
          supporting_text: 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
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        CHMP1A has cytoplasmic localization as documented in UniProt annotations.
      action: ACCEPT
      reason: >-
        Basic localization annotation consistent with UniProt subcellular location
        data.
        The cytoplasmic form is partially membrane-associated (UniProt).
      supported_by:
        - reference_id: PMID:11559748
          supporting_text: CHMP1 functions as a member of a newly defined family of
            vesicle trafficking proteins
  - term:
      id: GO:0005765
      label: lysosomal membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ESCRT-III components localize to lysosomal membranes in the context of autophagosome-lysosome
        fusion and MVB-lysosome fusion.
      action: ACCEPT
      reason: >-
        Consistent with ESCRT-III function in autophagy and endolysosomal trafficking.
        Experimental evidence from PMID:17984323 supports this localization.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: Functional multivesicular bodies are required for autophagic
            clearance
  - term:
      id: GO:0005828
      label: kinetochore microtubule
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ESCRT-III has roles at spindle microtubules. CHMP1A depletion affects spindle
        organization
        (PMID:20616062).
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: depletion of individual ESCRT-III and VPS4 proteins also
            altered centrosome and spindle pole numbers, producing multipolar spindles
  - term:
      id: GO:0006351
      label: DNA-templated transcription
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        CHMP1A was originally characterized as having chromatin-modifying activity
        and affecting
        gene expression through interaction with Polycomb group proteins.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:11559747
          supporting_text: CHMP1 can recruit a PcG protein, BMI1, to these regions
            of condensed chromatin
  - term:
      id: GO:0007034
      label: vacuolar transport
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      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.
      action: ACCEPT
      reason: >-
        InterPro-based annotation consistent with CHMP1A's role as an ESCRT-III/Snf7
        family member
        involved in endolysosomal trafficking.
  - term:
      id: GO:0007080
      label: mitotic metaphase chromosome alignment
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ESCRT-III depletion causes chromosome alignment defects. This is experimentally
        demonstrated for CHMP1A (PMID:20616062).
      action: KEEP_AS_NON_CORE
      reason: >-
        While CHMP1A depletion affects chromosome alignment, this is a secondary consequence
        of centrosome/spindle dysfunction rather than a direct function in alignment.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: causing defects in chromosome segregation and nuclear morphology
  - term:
      id: GO:0010008
      label: endosome membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        CHMP1A localizes to endosomal membranes as part of ESCRT-III function in MVB
        formation.
      action: ACCEPT
      reason: >-
        Core localization for ESCRT-III function. UniProt documents endosome membrane
        association.
      supported_by:
        - reference_id: PMID:11559748
          supporting_text: Immunocytochemistry and biochemical fractionation localize
            CHMP1 to early endosomes
  - term:
      id: GO:0015031
      label: protein transport
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        CHMP1A functions in protein transport as an ESCRT-III component involved in
        cargo sorting.
      action: ACCEPT
      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.
  - term:
      id: GO:0016363
      label: nuclear matrix
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        CHMP1A has a nuclear form that associates with the nuclear matrix, documented
        experimentally.
      action: ACCEPT
      reason: >-
        Experimentally validated localization (PMID:11559747). The nuclear form of
        CHMP1A remains
        associated with the chromosome scaffold during mitosis.
      supported_by:
        - reference_id: PMID:11559747
          supporting_text: 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
  - term:
      id: GO:0030496
      label: midbody
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        CHMP1A localizes to the midbody during cytokinesis as part of the ESCRT-III
        abscission machinery.
      action: ACCEPT
      reason: >-
        Core localization for cytokinetic function. ESCRT-III is recruited to the
        midbody
        for abscission (PMID:20616062, PMID:26040712).
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: VPS4 proteins concentrated at spindle poles during mitosis
            and then at midbodies during cytokinesis
  - term:
      id: GO:0031468
      label: nuclear membrane reassembly
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ESCRT-III is required for nuclear envelope reformation after mitosis.
        Two Nature papers in 2015 established this function.
      action: ACCEPT
      reason: >-
        Well-documented ESCRT-III function. PMID:26040712 and PMID:26040713 demonstrate
        ESCRT-III role in sealing the nuclear envelope during telophase.
      supported_by:
        - reference_id: PMID:26040713
          supporting_text: 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
  - term:
      id: GO:0032585
      label: multivesicular body membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        CHMP1A localizes to MVB membranes as part of ESCRT-III function in ILV formation.
      action: ACCEPT
      reason: >-
        Core localization. Experimentally supported by PMID:16554368.
      supported_by:
        - reference_id: PMID:16554368
          supporting_text: 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
  - term:
      id: GO:0039702
      label: viral budding via host ESCRT complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ESCRT-III is hijacked by enveloped viruses including HIV for budding. CHMP1A
        is part of this machinery.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:14505570
          supporting_text: The protein network of HIV budding
  - term:
      id: GO:0043162
      label: ubiquitin-dependent protein catabolic process via the multivesicular
        body sorting pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ESCRT-III sorts ubiquitinated cargo into ILVs for lysosomal degradation.
      action: ACCEPT
      reason: >-
        Core function of the ESCRT pathway. Ubiquitinated proteins are sorted into
        MVBs
        and delivered to lysosomes for degradation (PMID:17984323).
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: leading to accumulation of protein aggregates containing
            ubiquitinated proteins
  - term:
      id: GO:0046761
      label: viral budding from plasma membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ESCRT-III is used by viruses for budding from the plasma membrane.
      action: KEEP_AS_NON_CORE
      reason: >-
        Documented ESCRT-III function in viral budding (PMID:24878737), but represents
        viral exploitation rather than an endogenous function.
      supported_by:
        - reference_id: PMID:24878737
          supporting_text: Structure of cellular ESCRT-III spirals and their relationship
            to HIV budding
  - term:
      id: GO:0051301
      label: cell division
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        CHMP1A functions in cell division through its role in cytokinetic abscission
        and centrosome maintenance.
      action: ACCEPT
      reason: >-
        Well-supported by experimental evidence (PMID:20616062, PMID:19129479).
        ESCRT-III depletion blocks abscission.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human
            ESCRT-III (CHMP) proteins inhibited abscission
  - term:
      id: GO:0061952
      label: midbody abscission
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        CHMP1A is required for cytokinetic abscission at the midbody.
      action: ACCEPT
      reason: >-
        Core function. ESCRT-III mediates the final membrane fission step of cytokinesis.
        Depletion of CHMP1A impairs abscission (PMID:20616062, deep research).
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: The ESCRT pathway helps mediate the final abscission step
            of cytokinesis
  - term:
      id: GO:0071985
      label: multivesicular body sorting pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        CHMP1A is an ESCRT-III subunit essential for the MVB sorting pathway.
      action: ACCEPT
      reason: >-
        Core function. CHMP1A as part of ESCRT-III is required for MVB formation and
        cargo sorting (PMID:16554368).
      supported_by:
        - reference_id: PMID:16554368
          supporting_text: 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
  - term:
      id: GO:0097352
      label: autophagosome maturation
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ESCRT-III is required for autophagosome maturation and fusion with lysosomes.
      action: ACCEPT
      reason: >-
        Functional MVBs are required for autophagy (PMID:17984323). ESCRT depletion
        causes accumulation of protein aggregates due to impaired autophagic degradation.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: autophagic degradation is inhibited in cells depleted of
            ESCRT subunits
  - term:
      id: GO:1901673
      label: regulation of mitotic spindle assembly
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ESCRT-III/VPS4 depletion affects spindle assembly and centrosome numbers.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: depletion of individual ESCRT-III and VPS4 proteins also
            altered centrosome and spindle pole numbers
  - term:
      id: GO:1902774
      label: late endosome to lysosome transport
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        CHMP1A functions in late endosome to lysosome transport as part of ESCRT-III.
      action: ACCEPT
      reason: >-
        Core endolysosomal trafficking function. MVBs fuse with lysosomes to deliver
        cargo for degradation (PMID:17984323, PMID:16505166).
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: functional MVBs are required for clearance of TDP-43
  - term:
      id: GO:1904930
      label: amphisome membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        CHMP1A localizes to amphisome membranes, structures formed by autophagosome-endosome
        fusion.
      action: ACCEPT
      reason: >-
        Consistent with ESCRT-III function in autophagy and the requirement for
        functional MVBs in autophagic clearance (PMID:17984323).

# IPI annotations - protein binding
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16730941
    review:
      summary: >-
        CHMP1A binds multiple ESCRT-related proteins including STAMBP, CHMP1B, and
        VPS4A.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:16730941
          supporting_text: '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.'
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17711858
    review:
      summary: >-
        Documents UBPY (USP8) and STAMBP interactions with CHMP1A via MIT domains.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic protein binding. The paper documents specific interactions with deubiquitinating
        enzymes via MIT domain recognition of CHMP1A.
      supported_by:
        - reference_id: PMID:17711858
          supporting_text: 2007 Aug 21. The MIT domain of UBPY constitutes a CHMP
            binding and endosomal localization signal required for efficient epidermal
            growth factor receptor degradation.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19302785
    review:
      summary: >-
        Ab initio modeling identifies MIT domain proteins that interact with CHMP1A.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic protein binding annotation from a structural modeling study.
        More specific molecular function terms would be more informative.
      supported_by:
        - reference_id: PMID:19302785
          supporting_text: 2009 Feb 12. Ab initio protein modelling reveals novel
            human MIT domains.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21988832
    review:
      summary: >-
        High-throughput interactome study identifying CHMP1A interactions.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic protein binding from a large-scale study. Not informative
        about specific molecular function.
      supported_by:
        - reference_id: PMID:21988832
          supporting_text: Toward an understanding of the protein interaction network
            of the human liver.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:28514442
    review:
      summary: >-
        Large-scale interactome mapping study.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic protein binding annotation from high-throughput study.
      supported_by:
        - reference_id: PMID:28514442
          supporting_text: Architecture of the human interactome defines protein communities
            and disease networks.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32296183
    review:
      summary: >-
        Reference map of human binary protein interactome identifies CHMP1A interactions.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic protein binding from systematic interactome study.
      supported_by:
        - reference_id: PMID:32296183
          supporting_text: Apr 8. A reference map of the human binary protein interactome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32814053
    review:
      summary: >-
        Interactome study of neurodegenerative disease proteins identifies CHMP1A
        interactions
        with huntingtin (HTT), alpha-synuclein (SNCA).
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic protein binding. The interactions with disease proteins are interesting
        but the generic term is not informative.
      supported_by:
        - reference_id: PMID:32814053
          supporting_text: Interactome Mapping Provides a Network of Neurodegenerative
            Disease Proteins and Uncovers Widespread Protein Aggregation in Affected
            Brains.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:33961781
    review:
      summary: >-
        Dual proteome-scale network study.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic protein binding from high-throughput study.
      supported_by:
        - reference_id: PMID:33961781
          supporting_text: 2021 May 6. Dual proteome-scale networks reveal cell-specific
            remodeling of the human interactome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:35271311
    review:
      summary: >-
        OpenCell endogenous tagging study.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic protein binding annotation.
      supported_by:
        - reference_id: PMID:35271311
          supporting_text: '2022 Mar 11. OpenCell: Endogenous tagging for the cartography
            of human cellular organization.'
  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: IPI
    original_reference_id: PMID:16730941
    review:
      summary: >-
        CHMP1A self-associates to form polymeric assemblies characteristic of ESCRT-III.
      action: ACCEPT
      reason: >-
        ESCRT-III proteins self-associate to form membrane-remodeling polymers.
        This is a functionally important activity (PMID:16730941, UniProt).
      supported_by:
        - reference_id: PMID:14519844
          supporting_text: In particular, interactions between ESCRT-I and ESCRT-III
            are bridged by AIP-1/ALIX
        - reference_id: PMID:16730941
          supporting_text: '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.'
  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: IPI
    original_reference_id: PMID:32296183
    review:
      summary: >-
        Confirmation of CHMP1A self-association in systematic interactome study.
      action: ACCEPT
      reason: >-
        Duplicate evidence for self-association, which is functionally important
        for ESCRT-III polymer formation.

# IDA annotations - direct experimental evidence
      supported_by:
        - reference_id: PMID:32296183
          supporting_text: Apr 8. A reference map of the human binary protein interactome.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: >-
        HPA immunofluorescence data shows CHMP1A in nucleoplasm.
      action: ACCEPT
      reason: >-
        Consistent with CHMP1A having both cytoplasmic and nuclear forms (PMID:11559747).
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: >-
        HPA data shows cytosolic localization.
      action: ACCEPT
      reason: >-
        Consistent with UniProt annotation. ESCRT-III proteins cycle between
        cytosolic and membrane-associated states.
  - term:
      id: GO:0000421
      label: autophagosome membrane
    evidence_type: IDA
    original_reference_id: PMID:17984323
    review:
      summary: >-
        ESCRT-III localizes to autophagosome membranes where functional MVBs are required
        for autophagic clearance.
      action: ACCEPT
      reason: >-
        Experimentally demonstrated localization relevant to ESCRT-III function in
        autophagy.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: autophagic degradation is inhibited in cells depleted of
            ESCRT subunits
  - term:
      id: GO:0000776
      label: kinetochore
    evidence_type: IDA
    original_reference_id: PMID:26040712
    review:
      summary: >-
        ESCRT-III localizes to kinetochore regions during mitosis as demonstrated
        by imaging in this study.
      action: KEEP_AS_NON_CORE
      reason: >-
        While the localization is experimentally demonstrated, the functional significance
        of ESCRT-III at kinetochores is not fully characterized.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: CHMP3 and CHMP4, were recently reported to localize to
            kinetochores in a global screen for proteins with possible mitotic functions
        - reference_id: PMID:26040712
          supporting_text: Spastin and ESCRT-III coordinate mitotic spindle disassembly
            and nuclear envelope sealing.
  - term:
      id: GO:0001778
      label: plasma membrane repair
    evidence_type: IDA
    original_reference_id: PMID:24482116
    review:
      summary: >-
        ESCRT machinery is rapidly recruited to plasma membrane wounds and is required
        for repair.
      action: ACCEPT
      reason: >-
        Well-documented ESCRT-III function demonstrated with direct experimental evidence.
      supported_by:
        - reference_id: PMID:24482116
          supporting_text: ESCRT proteins were recruited within seconds to plasma
            membrane wounds...repair of certain wounds is ensured by ESCRT-mediated
            extracellular shedding
  - term:
      id: GO:0005765
      label: lysosomal membrane
    evidence_type: IDA
    original_reference_id: PMID:17984323
    review:
      summary: >-
        ESCRT-III localizes to lysosomal membranes in the context of autophagosome-lysosome
        fusion.
      action: ACCEPT
      reason: >-
        Experimentally demonstrated localization consistent with ESCRT-III role in
        autophagy and endolysosomal trafficking.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: Functional multivesicular bodies are required for autophagic
            clearance of protein aggregates associated with neurodegenerative disease.
  - term:
      id: GO:0005828
      label: kinetochore microtubule
    evidence_type: IDA
    original_reference_id: PMID:26040712
    review:
      summary: >-
        ESCRT-III localizes to spindle structures during mitosis.
      action: KEEP_AS_NON_CORE
      reason: >-
        Localization demonstrated but the direct functional role at kinetochore
        microtubules is not fully characterized for CHMP1A.
      supported_by:
        - reference_id: PMID:26040712
          supporting_text: Spastin and ESCRT-III coordinate mitotic spindle disassembly
            and nuclear envelope sealing.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: IDA
    original_reference_id: PMID:24878737
    review:
      summary: >-
        ESCRT-III spirals form at the plasma membrane during viral budding studies.
      action: ACCEPT
      reason: >-
        Experimentally demonstrated localization. ESCRT-III functions at the plasma
        membrane for viral budding and membrane repair.
      supported_by:
        - reference_id: PMID:24878737
          supporting_text: Structure of cellular ESCRT-III spirals and their relationship
            to HIV budding
  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: IMP
    original_reference_id: PMID:17984323
    review:
      summary: >-
        ESCRT depletion inhibits autophagic degradation, causing accumulation of
        protein aggregates.
      action: ACCEPT
      reason: >-
        Well-documented requirement for functional MVBs in autophagy.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: autophagic degradation is inhibited in cells depleted of
            ESCRT subunits
  - term:
      id: GO:0006997
      label: nucleus organization
    evidence_type: IMP
    original_reference_id: PMID:20616062
    review:
      summary: >-
        ESCRT-III depletion causes defects in nuclear morphology.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: causing defects in chromosome segregation and nuclear morphology
  - term:
      id: GO:0007080
      label: mitotic metaphase chromosome alignment
    evidence_type: IMP
    original_reference_id: PMID:20616062
    review:
      summary: >-
        ESCRT-III depletion causes chromosome alignment defects.
      action: KEEP_AS_NON_CORE
      reason: >-
        Chromosome alignment defects are likely secondary to spindle/centrosome
        dysfunction rather than a direct role in alignment.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: causing defects in chromosome segregation
  - term:
      id: GO:0030496
      label: midbody
    evidence_type: IDA
    original_reference_id: PMID:26040712
    review:
      summary: >-
        CHMP1A localizes to the midbody during cytokinesis.
      action: ACCEPT
      reason: >-
        Core localization for cytokinetic function. ESCRT-III is recruited to
        the midbody for abscission.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: VPS4 proteins concentrated...at midbodies during cytokinesis
        - reference_id: PMID:26040712
          supporting_text: Spastin and ESCRT-III coordinate mitotic spindle disassembly
            and nuclear envelope sealing.
  - term:
      id: GO:0031468
      label: nuclear membrane reassembly
    evidence_type: IMP
    original_reference_id: PMID:26040713
    review:
      summary: >-
        ESCRT-III is required for sealing the nuclear envelope during telophase.
      action: ACCEPT
      reason: >-
        Core function demonstrated by functional studies. ESCRT-III mediates annular
        fusion to seal the reforming nuclear envelope.
      supported_by:
        - reference_id: PMID:26040713
          supporting_text: 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
  - term:
      id: GO:0032585
      label: multivesicular body membrane
    evidence_type: IDA
    original_reference_id: PMID:16554368
    review:
      summary: >-
        ESCRT-III localizes to MVB membranes for ILV formation.
      action: ACCEPT
      reason: >-
        Core localization for ESCRT-III function in MVB biogenesis.
      supported_by:
        - reference_id: PMID:16554368
          supporting_text: 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
  - term:
      id: GO:0036258
      label: multivesicular body assembly
    evidence_type: NAS
    original_reference_id: PMID:16505166
    review:
      summary: >-
        CHMP1A participates in MVB assembly as an ESCRT-III subunit.
      action: ACCEPT
      reason: >-
        Core function. ESCRT-III is required for MVB assembly and ILV formation.
      supported_by:
        - reference_id: PMID:16505166
          supporting_text: Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated
            by a conserved VSL region in Vta1
  - term:
      id: GO:0039702
      label: viral budding via host ESCRT complex
    evidence_type: IDA
    original_reference_id: PMID:24878737
    review:
      summary: >-
        ESCRT-III spirals form during HIV budding as visualized in this structural
        study.
      action: KEEP_AS_NON_CORE
      reason: >-
        Documented ESCRT-III function but represents viral exploitation rather than
        endogenous function.
      supported_by:
        - reference_id: PMID:24878737
          supporting_text: Structure of cellular ESCRT-III spirals and their relationship
            to HIV budding
  - term:
      id: GO:0043162
      label: ubiquitin-dependent protein catabolic process via the multivesicular
        body sorting pathway
    evidence_type: IDA
    original_reference_id: PMID:17984323
    review:
      summary: >-
        ESCRT is required for degradation of ubiquitinated proteins via the MVB pathway.
      action: ACCEPT
      reason: >-
        Core ESCRT pathway function in targeting ubiquitinated proteins for lysosomal
        degradation.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: leading to accumulation of protein aggregates containing
            ubiquitinated proteins
  - term:
      id: GO:0046761
      label: viral budding from plasma membrane
    evidence_type: IDA
    original_reference_id: PMID:24878737
    review:
      summary: >-
        ESCRT-III forms spirals at the plasma membrane during HIV budding.
      action: KEEP_AS_NON_CORE
      reason: >-
        Documented ESCRT-III function in viral budding but represents viral
        exploitation of cellular machinery.
      supported_by:
        - reference_id: PMID:24878737
          supporting_text: Structure of cellular ESCRT-III spirals and their relationship
            to HIV budding.
  - term:
      id: GO:0051469
      label: vesicle fusion with vacuole
    evidence_type: NAS
    original_reference_id: PMID:16505166
    review:
      summary: >-
        ESCRT-III participates in MVB-lysosome fusion pathway.
      action: KEEP_AS_NON_CORE
      reason: >-
        While ESCRTs are involved in the MVB pathway, the direct role in
        fusion (as opposed to MVB formation) is less well characterized.
      supported_by:
        - reference_id: PMID:16505166
          supporting_text: Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated
            by a conserved VSL region in Vta1.
  - term:
      id: GO:0061763
      label: multivesicular body-lysosome fusion
    evidence_type: NAS
    original_reference_id: PMID:16505166
    review:
      summary: >-
        ESCRT function is required for MVB-lysosome fusion pathway.
      action: KEEP_AS_NON_CORE
      reason: >-
        The primary ESCRT-III role is in MVB formation rather than the fusion step,
        which involves SNARE machinery.
      supported_by:
        - reference_id: PMID:16505166
          supporting_text: Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated
            by a conserved VSL region in Vta1.
  - term:
      id: GO:0061952
      label: midbody abscission
    evidence_type: IMP
    original_reference_id: PMID:20616062
    review:
      summary: >-
        ESCRT-III depletion inhibits cytokinetic abscission.
      action: ACCEPT
      reason: >-
        Core function. ESCRT-III mediates the final membrane fission step of cytokinesis.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human
            ESCRT-III (CHMP) proteins inhibited abscission
  - term:
      id: GO:0071985
      label: multivesicular body sorting pathway
    evidence_type: IDA
    original_reference_id: PMID:16554368
    review:
      summary: >-
        CHMP1A functions in the MVB sorting pathway as an ESCRT-III subunit.
      action: ACCEPT
      reason: >-
        Core function. ESCRT-III is essential for the MVB sorting pathway.
      supported_by:
        - reference_id: PMID:16554368
          supporting_text: this ESCRT subunit, like Tsg101, is important for degradation
            of the epidermal growth factor (EGF) receptor (EGFR)
  - term:
      id: GO:0090148
      label: membrane fission
    evidence_type: NAS
    original_reference_id: PMID:19234443
    review:
      summary: >-
        ESCRT-III mediates membrane scission at MVBs, midbody, and other sites.
      action: ACCEPT
      reason: >-
        Core molecular function of ESCRT-III. The complex mediates topologically
        equivalent membrane fission events.
      supported_by:
        - reference_id: PMID:19234443
          supporting_text: Membrane scission by the ESCRT-III complex
  - term:
      id: GO:0097352
      label: autophagosome maturation
    evidence_type: IMP
    original_reference_id: PMID:17984323
    review:
      summary: >-
        Functional MVBs are required for autophagosome maturation and autophagic clearance.
      action: ACCEPT
      reason: >-
        Experimentally demonstrated. ESCRT depletion causes accumulation of protein
        aggregates.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: autophagic degradation is inhibited in cells depleted of
            ESCRT subunits
  - term:
      id: GO:1901673
      label: regulation of mitotic spindle assembly
    evidence_type: IMP
    original_reference_id: PMID:20616062
    review:
      summary: >-
        ESCRT-III depletion affects spindle organization.
      action: KEEP_AS_NON_CORE
      reason: >-
        Spindle defects likely result from centrosome dysfunction rather than
        direct regulation of spindle assembly.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: depletion of individual ESCRT-III and VPS4 proteins also
            altered centrosome and spindle pole numbers
  - term:
      id: GO:1902774
      label: late endosome to lysosome transport
    evidence_type: IMP
    original_reference_id: PMID:17984323
    review:
      summary: >-
        ESCRT is required for efficient transport from late endosomes to lysosomes.
      action: ACCEPT
      reason: >-
        Core endolysosomal trafficking function demonstrated by functional studies.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: functional MVBs are required for clearance
  - term:
      id: GO:1904930
      label: amphisome membrane
    evidence_type: IDA
    original_reference_id: PMID:17984323
    review:
      summary: >-
        ESCRT-III localizes to amphisome membranes.
      action: ACCEPT
      reason: >-
        Consistent with ESCRT-III function in autophagy. Amphisomes are intermediates
        in autophagosome-lysosome fusion.
      supported_by:
        - reference_id: PMID:17984323
          supporting_text: Functional multivesicular bodies are required for autophagic
            clearance of protein aggregates associated with neurodegenerative disease.
  - term:
      id: GO:0007076
      label: mitotic chromosome condensation
    evidence_type: IDA
    original_reference_id: PMID:11559747
    review:
      summary: >-
        CHMP1A was originally characterized as affecting chromatin condensation.
        Overexpressed CHMP1A localizes to condensed chromatin.
      action: KEEP_AS_NON_CORE
      reason: >-
        While documented in the original characterization paper, this appears to be
        a secondary nuclear function. The IDA evidence is based on overexpression.
      supported_by:
        - reference_id: PMID:11559747
          supporting_text: Overexpressed CHMP1 localizes to a punctate subnuclear
            pattern, encapsulating regions of nuclease-resistant, condensed chromatin
  - term:
      id: GO:0010629
      label: negative regulation of gene expression
    evidence_type: IDA
    original_reference_id: PMID:11559747
    review:
      summary: >-
        CHMP1A recruits BMI1 and affects gene silencing through Polycomb group interaction.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary nuclear function. The PcG interaction is documented but is not
        the primary ESCRT-III membrane fission function.
      supported_by:
        - reference_id: PMID:11559747
          supporting_text: CHMP1 can recruit a PcG protein, BMI1, to these regions
            of condensed chromatin...consistent with a role in PcG function

# TAS annotations
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9610942
    review:
      summary: >-
        Reactome annotation for HCMV final envelopment complex formation.
      action: ACCEPT
      reason: >-
        Cytosolic localization is consistent with ESCRT-III biology.
        The soluble pool is recruited to membranes upon activation.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9610954
    review:
      summary: >-
        Reactome annotation for HCMV final envelopment.
      action: ACCEPT
      reason: >-
        Duplicate cytosol annotation from Reactome pathway.
  - term:
      id: GO:0036258
      label: multivesicular body assembly
    evidence_type: NAS
    original_reference_id: PMID:20588296
    review:
      summary: >-
        Review article on ESCRT-mediated membrane budding and scission.
      action: ACCEPT
      reason: >-
        Core function of ESCRT-III in MVB assembly is well established.
      supported_by:
        - reference_id: PMID:20588296
          supporting_text: Membrane budding and scission by the ESCRT machinery
  - term:
      id: GO:0039702
      label: viral budding via host ESCRT complex
    evidence_type: NAS
    original_reference_id: PMID:20588296
    review:
      summary: >-
        Review discusses ESCRT role in viral budding.
      action: KEEP_AS_NON_CORE
      reason: >-
        Viral budding is a documented ESCRT function but represents exploitation
        of cellular machinery.
      supported_by:
        - reference_id: PMID:20588296
          supporting_text: "Jun 30. Membrane budding and scission by the ESCRT machinery:\
            \ it's all in the neck."
  - term:
      id: GO:1904903
      label: ESCRT III complex disassembly
    evidence_type: NAS
    original_reference_id: PMID:20588296
    review:
      summary: >-
        VPS4 disassembles ESCRT-III polymers. CHMP1A participates in this cycle.
      action: ACCEPT
      reason: >-
        VPS4-mediated disassembly is essential for ESCRT-III recycling and function.
      supported_by:
        - reference_id: PMID:16505166
          supporting_text: Recycling of ESCRTs by the AAA-ATPase Vps4
        - reference_id: PMID:20588296
          supporting_text: "Jun 30. Membrane budding and scission by the ESCRT machinery:\
            \ it's all in the neck."
  - term:
      id: GO:0051301
      label: cell division
    evidence_type: IMP
    original_reference_id: PMID:19129479
    review:
      summary: >-
        IST1 functional studies demonstrate requirement for ESCRT-III in cell division.
      action: ACCEPT
      reason: >-
        Core function. ESCRT-III is required for cytokinetic abscission.
      supported_by:
        - reference_id: PMID:19129479
          supporting_text: Biochemical analyses of human IST1 and its function in
            cytokinesis
  - term:
      id: GO:0010824
      label: regulation of centrosome duplication
    evidence_type: IMP
    original_reference_id: PMID:20616062
    review:
      summary: >-
        ESCRT-III depletion causes centrosome amplification.
      action: KEEP_AS_NON_CORE
      reason: >-
        Centrosome defects are observed but the mechanistic role is not fully understood.
        May involve indirect effects through endosomal trafficking.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: approximately 80% of HeLa cells lacking VPS4B exhibited
            multiple centrosomes

# Additional IPI annotations
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:14519844
    review:
      summary: >-
        Documents CHMP1A interactions with CHMP1B and VPS4A in the context of
        retroviral budding.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic protein binding. The specific interactions documented are
        more informative than this generic term.
      supported_by:
        - reference_id: PMID:14519844
          supporting_text: Divergent retroviral late-budding domains recruit vacuolar
            protein sorting factors by using alternative adaptor proteins.
  - term:
      id: GO:0042803
      label: protein homodimerization activity
    evidence_type: IPI
    original_reference_id: PMID:14519844
    review:
      summary: >-
        CHMP1A self-associates.
      action: ACCEPT
      reason: >-
        Self-association is important for ESCRT-III polymer formation.
      supported_by:
        - reference_id: PMID:14519844
          supporting_text: Divergent retroviral late-budding domains recruit vacuolar
            protein sorting factors
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:14505570
    review:
      summary: >-
        HIV budding protein network study documenting ESCRT interactions.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic protein binding. Specific interactions with VPS4A, VPS4B,
        CHMP1B are more informative.
      supported_by:
        - reference_id: PMID:14505570
          supporting_text: The protein network of HIV budding.
  - term:
      id: GO:0042803
      label: protein homodimerization activity
    evidence_type: IPI
    original_reference_id: PMID:14505570
    review:
      summary: >-
        CHMP1A self-association documented.
      action: ACCEPT
      reason: >-
        Functionally important self-association for polymer formation.
      supported_by:
        - reference_id: PMID:14505570
          supporting_text: The protein network of HIV budding.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23045692
    review:
      summary: >-
        Documents CHMP1A interaction with MITD1 via C-terminal motif.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic protein binding. The specific interaction with MITD1 for
        cytokinesis is more informative.
      supported_by:
        - reference_id: PMID:23045692
          supporting_text: ESCRT-III binding protein MITD1 is involved in cytokinesis
            and has an unanticipated PLD fold that binds membranes.
  - term:
      id: GO:0070062
      label: extracellular exosome
    evidence_type: HDA
    original_reference_id: PMID:19056867
    review:
      summary: >-
        CHMP1A identified in urinary exosome proteomics.
      action: KEEP_AS_NON_CORE
      reason: >-
        Detection in exosomes may reflect ESCRT-III role in MVB/exosome biogenesis
        or could be incidental. Not a core localization.
      supported_by:
        - reference_id: PMID:19056867
          supporting_text: 2008 Dec 3. Large-scale proteomics and phosphoproteomics
            of urinary exosomes.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19129480
    review:
      summary: >-
        IST1 binds CHMP1A for cytokinesis function.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic protein binding. The specific IST1 interaction is documented
        in the protein domain specific binding annotation.
      supported_by:
        - reference_id: PMID:19129480
          supporting_text: Jan 7. Essential role of hIST1 in cytokinesis.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19129479
    review:
      summary: >-
        Biochemical study of IST1-CHMP1A interaction.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic protein binding.
      supported_by:
        - reference_id: PMID:19129479
          supporting_text: Jan 7. Biochemical analyses of human IST1 and its function
            in cytokinesis.
  - term:
      id: GO:0019904
      label: protein domain specific binding
    evidence_type: IPI
    original_reference_id: PMID:17928862
    review:
      summary: >-
        CHMP1A C-terminal MIM motif binds VPS4 MIT domain. Structural characterization
        of the interaction.
      action: ACCEPT
      reason: >-
        Specific and functionally important interaction. The VPS4 MIT domain
        recognizes ESCRT-III MIM motifs for complex disassembly.
      supported_by:
        - reference_id: PMID:17928862
          supporting_text: ESCRT-III recognition by VPS4 ATPases

# Erroneous TAS annotations from original PRSM1 characterization
  - term:
      id: GO:0008237
      label: metallopeptidase activity
    evidence_type: TAS
    original_reference_id: PMID:8863740
    review:
      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.
      action: REMOVE
      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.
      additional_reference_ids: ["UniProt:Q9HD42"]
      supported_by:
        - reference_id: PMID:8863740
          supporting_text: Molecular cloning, expression and chromosomal localization
            of a human gene encoding a 33 kDa putative metallopeptidase (PRSM1).
  - term:
      id: GO:0008270
      label: zinc ion binding
    evidence_type: TAS
    original_reference_id: PMID:8863740
    review:
      summary: >-
        This annotation is erroneous, arising from the same mistranslation that
        led to the incorrect metallopeptidase annotation.
      action: REMOVE
      reason: >-
        Based on erroneous translation of the gene. There is no evidence that
        CHMP1A binds zinc. UniProt documents this error.
      additional_reference_ids:
        - UniProt:Q9HD42

# More IPI annotations
      supported_by:
        - reference_id: PMID:8863740
          supporting_text: Molecular cloning, expression and chromosomal localization
            of a human gene encoding a 33 kDa putative metallopeptidase (PRSM1).
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:11559748
    review:
      summary: >-
        Original CHMP1 characterization documenting VPS4A interaction.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic protein binding. The VPS4A interaction is captured in more
        specific annotations.
      supported_by:
        - reference_id: PMID:11559748
          supporting_text: CHMP1 functions as a member of a newly defined family of
            vesicle trafficking proteins.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:12445808
    review:
      summary: >-
        Hepatitis C virus NS4B interaction with CHMP1A identified.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic protein binding from virus-host interaction study. The biological
        significance is unclear.

# Additional localization annotations
      supported_by:
        - reference_id: PMID:12445808
          supporting_text: Physical interaction between hepatitis C virus NS4B protein
            and CREB-RP/ATF6beta.
  - term:
      id: GO:0000794
      label: condensed nuclear chromosome
    evidence_type: IDA
    original_reference_id: PMID:11559747
    review:
      summary: >-
        CHMP1A localizes to condensed chromatin upon overexpression.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary nuclear function documented in the original characterization.
        Overexpression study, may not reflect physiological localization.
      supported_by:
        - reference_id: PMID:11559747
          supporting_text: Overexpressed CHMP1 localizes to a punctate subnuclear
            pattern, encapsulating regions of nuclease-resistant, condensed chromatin
  - term:
      id: GO:0005769
      label: early endosome
    evidence_type: IDA
    original_reference_id: PMID:11559748
    review:
      summary: >-
        CHMP1A localizes to early endosomes.
      action: ACCEPT
      reason: >-
        Consistent with ESCRT-III recruitment to endosomes. The cytoplasmic form
        is partially membrane-associated and localizes to early endosomes.
      supported_by:
        - reference_id: PMID:11559748
          supporting_text: CHMP1 functions as a member of a newly defined family of
            vesicle trafficking proteins
  - term:
      id: GO:0005815
      label: microtubule organizing center
    evidence_type: IDA
    original_reference_id: PMID:11559748
    review:
      summary: >-
        CHMP1A localizes to MTOC/centrosome.
      action: KEEP_AS_NON_CORE
      reason: >-
        Centrosomal localization is documented and ESCRT-III depletion affects
        centrosome numbers (PMID:20616062), but the functional role at
        centrosomes is not fully characterized.
      supported_by:
        - reference_id: PMID:20616062
          supporting_text: depletion of individual ESCRT-III and VPS4 proteins also
            altered centrosome and spindle pole numbers
        - reference_id: PMID:11559748
          supporting_text: CHMP1 functions as a member of a newly defined family of
            vesicle trafficking proteins.
  - term:
      id: GO:0012505
      label: endomembrane system
    evidence_type: IDA
    original_reference_id: PMID:11559748
    review:
      summary: >-
        CHMP1A is part of the endomembrane system as an ESCRT-III component.
      action: ACCEPT
      reason: >-
        Appropriate general localization for an ESCRT-III protein that functions
        at endosomes and other membrane compartments.
      supported_by:
        - reference_id: PMID:11559748
          supporting_text: CHMP1 functions as a member of a newly defined family of
            vesicle trafficking proteins.
  - term:
      id: GO:0016192
      label: vesicle-mediated transport
    evidence_type: IDA
    original_reference_id: PMID:11559748
    review:
      summary: >-
        CHMP1A functions in vesicle trafficking as an ESCRT-III component.
      action: ACCEPT
      reason: >-
        Core function. ESCRT-III mediates vesicle formation at MVBs.
      supported_by:
        - reference_id: PMID:11559748
          supporting_text: CHMP1 functions as a member of a newly defined family of
            vesicle trafficking proteins
  - term:
      id: GO:0016363
      label: nuclear matrix
    evidence_type: IDA
    original_reference_id: PMID:11559747
    review:
      summary: >-
        CHMP1A has a nuclear form that associates with the nuclear matrix.
      action: ACCEPT
      reason: >-
        Experimentally validated localization. CHMP1 distributes to both
        cytoplasm and nuclear matrix.
      supported_by:
        - reference_id: PMID:11559747
          supporting_text: 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
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with GO
      terms
    findings:
      - statement: CHMP1A contains the Snf7 family domain characteristic of ESCRT-III
          proteins.
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings:
      - statement: Phylogenetic analysis supports CHMP1A as an ESCRT-III subunit with
          conserved MVB sorting function.
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
    findings: []
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
      vocabulary mapping
    findings: []
  - id: GO_REF:0000052
    title: Gene Ontology annotation based on curation of immunofluorescence data
    findings: []
  - id: GO_REF:0000117
    title: Electronic Gene Ontology annotations created by ARBA machine learning models
    findings: []
  - id: PMID:11559747
    title: CHMP1 is a novel nuclear matrix protein affecting chromatin structure and
      cell-cycle progression.
    findings:
      - statement: >-
          Original characterization of CHMP1A showing nuclear matrix localization
          and
          chromatin condensation effects through Polycomb group protein interaction.
  - id: PMID:11559748
    title: CHMP1 functions as a member of a newly defined family of vesicle trafficking
      proteins.
    findings:
      - statement: >-
          Characterization of CHMP1A as a VPS4-interacting protein involved in vesicle
          trafficking
          with early endosome and MTOC localization.
  - id: PMID:12445808
    title: Physical interaction between hepatitis C virus NS4B protein and CREB-RP/ATF6beta.
    findings: []
  - id: PMID:14505570
    title: The protein network of HIV budding.
    findings:
      - statement: >-
          Systematic analysis of HIV budding protein network identifying CHMP1A interactions
          with VPS4A, VPS4B, and CHMP1B.
  - id: PMID:14519844
    title: Divergent retroviral late-budding domains recruit vacuolar protein sorting
      factors by using alternative adaptor proteins.
    findings:
      - statement: CHMP1A self-associates and interacts with CHMP1B and VPS4A.
  - id: PMID:16505166
    title: Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved
      VSL region in Vta1.
    findings:
      - statement: VPS4 recycles ESCRT-III components including CHMP1A after membrane
          fission.
  - id: PMID:16554368
    title: The ESCRT-III subunit hVps24 is required for degradation but not silencing
      of the epidermal growth factor receptor.
    findings:
      - statement: ESCRT-III is required for EGFR degradation via the MVB pathway.
  - id: PMID:16730941
    title: A systematic analysis of human CHMP protein interactions; additional MIT
      domain-containing proteins bind to multiple components of the human ESCRT III
      complex.
    findings:
      - statement: Systematic mapping of CHMP1A interactions with MIT domain proteins.
  - id: PMID:17711858
    title: The MIT domain of UBPY constitutes a CHMP binding and endosomal localization
      signal required for efficient epidermal growth factor receptor degradation.
    findings:
      - statement: UBPY/USP8 MIT domain interacts with CHMP proteins including CHMP1A.
  - id: PMID:17928862
    title: ESCRT-III recognition by VPS4 ATPases.
    findings:
      - statement: >-
          Structural characterization of VPS4 MIT domain recognition of CHMP1A MIM
          motif
          (residues 180-196).
  - id: PMID:17984323
    title: Functional multivesicular bodies are required for autophagic clearance
      of protein aggregates associated with neurodegenerative disease.
    findings:
      - statement: >-
          ESCRT depletion inhibits autophagic degradation, causing accumulation of
          ubiquitinated protein aggregates. Functional MVBs are required for autophagy.
  - id: PMID:19056867
    title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
    findings: []
  - id: PMID:19129479
    title: Biochemical analyses of human IST1 and its function in cytokinesis.
    findings:
      - statement: IST1 interacts with CHMP1A and is required for cytokinesis.
  - id: PMID:19129480
    title: Essential role of hIST1 in cytokinesis.
    findings:
      - statement: IST1 binds CHMP1A and functions in cytokinetic abscission.
  - id: PMID:19234443
    title: Membrane scission by the ESCRT-III complex.
    findings:
      - statement: ESCRT-III mediates membrane scission at MVBs and other sites.
  - id: PMID:19302785
    title: Ab initio protein modelling reveals novel human MIT domains.
    findings: []
  - id: PMID:20588296
    title: "Membrane budding and scission by the ESCRT machinery: it's all in the\
      \ neck."
    findings:
      - statement: Review of ESCRT-mediated membrane fission mechanism.
  - id: PMID:20616062
    title: Human ESCRT-III and VPS4 proteins are required for centrosome and spindle
      maintenance.
    findings:
      - statement: >-
          Systematic analysis showing all 11 ESCRT-III proteins including CHMP1A are
          required
          for abscission. Depletion causes centrosome amplification and spindle defects.
  - id: PMID:21988832
    title: Toward an understanding of the protein interaction network of the human
      liver.
    findings: []
  - id: PMID:23045692
    title: ESCRT-III binding protein MITD1 is involved in cytokinesis and has an unanticipated
      PLD fold that binds membranes.
    findings:
      - statement: MITD1 binds CHMP1A and functions in cytokinesis.
  - id: PMID:24482116
    title: ESCRT machinery is required for plasma membrane repair.
    findings:
      - statement: >-
          ESCRTs are recruited within seconds to plasma membrane wounds and mediate
          repair
          via extracellular shedding of damaged membrane.
  - id: PMID:24878737
    title: Structure of cellular ESCRT-III spirals and their relationship to HIV budding.
    findings:
      - statement: ESCRT-III forms spirals at the plasma membrane during viral budding.
  - id: PMID:26040712
    title: Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear
      envelope sealing.
    findings:
      - statement: >-
          ESCRT-III is recruited to the reforming nuclear envelope where it coordinates
          with spastin for spindle microtubule severing and NE sealing.
  - id: PMID:26040713
    title: ESCRT-III controls nuclear envelope reformation.
    findings:
      - statement: >-
          ESCRT-III localizes to sites of annular fusion in the forming nuclear envelope
          and is required for proper nucleo-cytoplasmic compartmentalization.
  - id: PMID:28514442
    title: Architecture of the human interactome defines protein communities and disease
      networks.
    findings: []
  - id: PMID:32296183
    title: A reference map of the human binary protein interactome.
    findings: []
  - id: PMID:32814053
    title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
      and Uncovers Widespread Protein Aggregation in Affected Brains.
    findings:
      - statement: CHMP1A interacts with huntingtin and alpha-synuclein.
  - id: PMID:33961781
    title: Dual proteome-scale networks reveal cell-specific remodeling of the human
      interactome.
    findings: []
  - id: PMID:35271311
    title: OpenCell Endogenous tagging for the cartography of human cellular organization.
    findings: []
  - id: PMID:8863740
    title: Molecular cloning, expression and chromosomal localization of a human gene
      encoding a 33 kDa putative metallopeptidase (PRSM1).
    findings:
      - statement: >-
          ERRONEOUS - This paper incorrectly translated the ORF and proposed metallopeptidase
          function. UniProt notes this error.
  - id: Reactome:R-HSA-9610942
    title: HCMV Formation of Final Envelopment Complex
    findings: []
  - id: Reactome:R-HSA-9610954
    title: HCMV Final Envelopment
    findings: []
  - id: file:human/CHMP1A/CHMP1A-deep-research-falcon.md
    title: Deep research report on CHMP1A
    findings: []
core_functions:
  - description: >-
      ESCRT-III subunit function in MVB formation and cargo sorting. CHMP1A is a core
      component
      of the ESCRT-III complex that polymerizes at the neck of forming intraluminal
      vesicles
      and mediates membrane fission in coordination with VPS4 ATPases.
    molecular_function:
      id: GO:0042802
      label: identical protein binding
    directly_involved_in:
      - id: GO:0036258
        label: multivesicular body assembly
    locations:
      - id: GO:0032585
        label: multivesicular body membrane
    supported_by:
      - reference_id: PMID:16554368
        supporting_text: 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
    in_complex:
      id: GO:0000815
      label: ESCRT III complex
  - description: >-
      Cytokinetic abscission. CHMP1A is recruited to the midbody during the final
      stage of
      cell division where ESCRT-III mediates the membrane fission step that separates
      daughter cells.
    molecular_function:
      id: GO:0042802
      label: identical protein binding
    directly_involved_in:
      - id: GO:0061952
        label: midbody abscission
    locations:
      - id: GO:0030496
        label: midbody
    supported_by:
      - reference_id: PMID:20616062
        supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human
          ESCRT-III (CHMP) proteins inhibited abscission
  - description: >-
      Nuclear envelope reformation. CHMP1A as part of ESCRT-III is transiently recruited
      to
      the reforming nuclear envelope during telophase where it mediates annular fusion
      to
      seal the envelope and ensure nuclear integrity.
    molecular_function:
      id: GO:0042802
      label: identical protein binding
    directly_involved_in:
      - id: GO:0031468
        label: nuclear membrane reassembly
    supported_by:
      - reference_id: PMID:26040713
        supporting_text: 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
    in_complex:
      id: GO:0000815
      label: ESCRT III complex
  - description: >-
      Autophagosome maturation. CHMP1A contributes to autophagy by participating in
      ESCRT-III-dependent processes required for autophagosome-lysosome fusion and
      autophagic clearance of protein aggregates.
    molecular_function:
      id: GO:0042802
      label: identical protein binding
    directly_involved_in:
      - id: GO:0097352
        label: autophagosome maturation
    locations:
      - id: GO:0000421
        label: autophagosome membrane
    supported_by:
      - reference_id: PMID:17984323
        supporting_text: autophagic degradation is inhibited in cells depleted of
          ESCRT subunits and in cells expressing CHMP2B mutants, leading to accumulation
          of protein aggregates containing ubiquitinated proteins
  - description: >-
      Plasma membrane repair. ESCRT-III including CHMP1A is rapidly recruited to sites
      of
      plasma membrane damage where it mediates repair through extracellular shedding
      of
      wounded membrane portions.
    molecular_function:
      id: GO:0042802
      label: identical protein binding
    directly_involved_in:
      - id: GO:0001778
        label: plasma membrane repair
    locations:
      - id: GO:0005886
        label: plasma membrane
    supported_by:
      - reference_id: PMID:24482116
        supporting_text: ESCRT proteins were recruited within seconds to plasma membrane
          wounds
proposed_new_terms: []
suggested_questions:
  - question: What is the specific contribution of CHMP1A vs CHMP1B to ESCRT-III function
      at different cellular sites?
    experts: [Stenmark H]
  - question: How is CHMP1A recruitment specifically regulated at the nuclear envelope
      vs midbody vs MVBs?
    experts: [Stenmark H, Saksena S]
  - question: What is the mechanistic basis for the centrosome phenotypes observed
      upon ESCRT-III depletion?
    experts: [Bhutta MS]
suggested_experiments:
  - description: 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
    experiment_type: Rescue assay
  - description: 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
    experiment_type: Live cell imaging
  - description: Proximity labeling (BioID/APEX) to identify site-specific CHMP1A
      interaction partners
    hypothesis: CHMP1A interacts with different proteins at different cellular locations
    experiment_type: Proximity proteomics