CAPG

id: P40121
gene_symbol: CAPG
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  CAPG (macrophage-capping protein, gCap39) is a calcium-sensitive actin-binding protein
  belonging to the gelsolin/villin superfamily. It contains three gelsolin-like domains
  (C1-C3) and functions primarily as a barbed-end actin filament capping protein,
  reversibly blocking barbed ends to modulate actin filament dynamics. Critically,
  CAPG does NOT sever actin filaments, distinguishing it from gelsolin. The protein
  is regulated by calcium (activating) and phosphatidylinositol-4,5-bisphosphate (PIP2,
  antagonizes capping), enabling rapid and reversible control during cell signaling
  and membrane remodeling. CAPG also contains redox-sensitive cysteines (C282/C290)
  that affect its localization and migration function. The protein localizes to both
  cytoplasm and nucleus, with dynamic nucleo-cytoplasmic shuttling via importin-beta/NTF2/Ran-dependent
  nuclear import. In macrophages, CAPG is particularly abundant and concentrated at
  ruffles and leading lamellipodia. CAPG is overexpressed in multiple cancers and
  promotes invasion and migration.
existing_annotations:
  - term:
      id: GO:0015629
      label: actin cytoskeleton
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        CAPG is a member of the gelsolin/villin family that functions in actin cytoskeleton
        regulation. UniProt indicates localization at the membrane-cytoplasm interface
        and at lamellipodia/ruffles in activated macrophages. CAPG's primary function
        as a barbed-end actin capping protein directly implicates it in actin cytoskeleton
        organization.
      action: ACCEPT
      reason: >-
        CAPG is an actin-binding protein that caps barbed ends of actin filaments
        (PMID:1322908),
        placing it firmly within the actin cytoskeleton. This IBA annotation is well-supported
        by phylogenetic inference within the gelsolin family.
      supported_by:
        - reference_id: PMID:1322908
          supporting_text: >-
            Macrophage capping protein (MCP) is a Ca(2+)-sensitive protein which reversibly
            blocks the barbed ends of actin filaments
        - reference_id: file:human/CAPG/CAPG-deep-research-falcon.md
          supporting_text: >-
            CAPG is the human macrophage-capping protein (also called gCap39) belonging
            to the gelsolin/villin superfamily
  - term:
      id: GO:0051015
      label: actin filament binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        CAPG binds actin filaments at their barbed ends to cap them. This is the core
        biochemical activity of the protein. Deep research confirms CAPG binds actin
        monomers and can influence nucleation/polymerization kinetics.
      action: ACCEPT
      reason: >-
        Actin filament binding is the fundamental molecular function of CAPG. The
        protein
        binds specifically to barbed ends of actin filaments to cap them, as demonstrated
        in the original characterization (PMID:1322908).
      supported_by:
        - reference_id: PMID:1322908
          supporting_text: >-
            Macrophage capping protein (MCP) is a Ca(2+)-sensitive protein which reversibly
            blocks the barbed ends of actin filaments but does not sever preformed
            actin filaments
        - reference_id: file:human/CAPG/CAPG-deep-research-falcon.md
          supporting_text: >-
            Binds actin monomers and can influence nucleation/polymerization kinetics;
            lower actin-binding affinity than full-length gelsolin
  - term:
      id: GO:0008154
      label: actin polymerization or depolymerization
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        CAPG affects actin dynamics by capping barbed ends, thereby influencing the
        balance of polymerization/depolymerization. By blocking barbed ends, CAPG
        prevents
        monomer addition at that site, affecting overall filament dynamics.
      action: ACCEPT
      reason: >-
        By capping barbed ends of actin filaments, CAPG directly influences actin
        polymerization
        dynamics. The original paper demonstrates CAPG's ability to block monomer
        exchange
        at the barbed end, which affects polymerization.
      supported_by:
        - reference_id: PMID:1322908
          supporting_text: >-
            ability to block monomer exchange at the barbed end of actin filaments
        - reference_id: file:human/CAPG/CAPG-deep-research-falcon.md
          supporting_text: >-
            CAPG caps actin filament barbed ends to tune filament elongation
  - term:
      id: GO:0051014
      label: actin filament severing
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        This annotation is INCORRECT for CAPG. Unlike gelsolin (which has 6 domains
        and
        severs filaments), CAPG (with only 3 domains) does NOT sever actin filaments.
        This is a well-established distinction in the gelsolin family. The original
        1992 paper explicitly states CAPG does not sever preformed actin filaments.
        While engineered mutants can acquire severing activity (PMID:7814409), the
        native wild-type protein lacks this function.
      action: REMOVE
      reason: >-
        CAPG explicitly does NOT sever actin filaments. The original characterization
        (PMID:1322908) states unambiguously that CAPG "does not sever preformed actin
        filaments." This is a key functional distinction between CAPG (3 gelsolin
        domains,
        capping only) and gelsolin (6 domains, severing + capping). The IBA annotation
        appears to be an over-extension from the gelsolin family, but CAPG specifically
        lacks severing activity. Deep research confirms "native CAPG does not sever
        filaments under typical conditions."
      supported_by:
        - reference_id: PMID:1322908
          supporting_text: >-
            Macrophage capping protein (MCP) is a Ca(2+)-sensitive protein which reversibly
            blocks the barbed ends of actin filaments but does not sever preformed
            actin
            filaments
        - reference_id: file:human/CAPG/CAPG-deep-research-falcon.md
          supporting_text: >-
            In contrast to gelsolin, native CAPG does not sever filaments under typical
            conditions, although engineered mutants can acquire severing activity
  - term:
      id: GO:0005546
      label: phosphatidylinositol-4,5-bisphosphate binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        PIP2 is a key regulator of CAPG activity. PIP2 binding antagonizes CAPG's
        actin-capping activity, allowing for spatiotemporal control at membranes and
        leading edges.
      action: ACCEPT
      reason: >-
        PIP2 regulation is a well-established feature of CAPG and gelsolin-family
        proteins.
        PIP2 antagonizes capping activity, enabling rapid and reversible control during
        cell signaling and membrane remodeling.
      supported_by:
        - reference_id: file:human/CAPG/CAPG-deep-research-falcon.md
          supporting_text: >-
            Activity is Ca2+-sensitive and regulated by polyphosphoinositides (PIP2)
            which
            can antagonize capping; regulation is rapid and reversible
        - reference_id: file:human/CAPG/CAPG-deep-research-falcon.md
          supporting_text: >-
            Ca2+ promotes active conformations of the gelsolin-like domains; PIP2
            binding
            antagonizes capping, allowing leading-edge control
  - term:
      id: GO:0007417
      label: central nervous system development
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        CAPG's role in CNS development is likely a pleiotropic effect of its core
        actin-regulatory function rather than a specific dedicated function. While
        actin dynamics are crucial for neuronal development and migration, this represents
        a downstream biological process rather than CAPG's core function.
      action: KEEP_AS_NON_CORE
      reason: >-
        CNS development requires actin cytoskeleton remodeling, and CAPG may contribute
        through its general actin-capping activity. However, this is not the core
        function
        of CAPG. The annotation should be retained as non-core to indicate CAPG's
        involvement in broader biological processes while not representing its primary
        molecular function.
      supported_by:
        - reference_id: file:human/CAPG/CAPG-deep-research-falcon.md
          supporting_text: >-
            CAPG acts at the cell cortex and adhesion complexes to influence protrusion
            and motility
  - term:
      id: GO:0030031
      label: cell projection assembly
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        CAPG localizes to lamellipodia and membrane ruffles in activated macrophages,
        where it caps actin filaments. This is directly relevant to cell projection
        assembly as CAPG regulates actin dynamics at the leading edge.
      action: ACCEPT
      reason: >-
        CAPG is concentrated at ruffles of leading lamellipodia in activated macrophages
        and regulates actin dynamics at the cell cortex. Cell projection assembly
        is
        a direct functional consequence of CAPG's actin-capping activity at the
        membrane-cytoplasm interface.
      supported_by:
        - reference_id: PMID:1322908
          supporting_text: >-
            its abundance in macrophages... indicate that MCP may play an important
            role
            in macrophage function
        - reference_id: file:human/CAPG/CAPG-uniprot.txt
          supporting_text: >-
            In activated macrophages, concentrated in the ruffles of the leading lamellipodia
  - term:
      id: GO:0051016
      label: barbed-end actin filament capping
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        Barbed-end actin filament capping is the CORE molecular function of CAPG.
        The protein reversibly blocks barbed ends of actin filaments to regulate
        filament dynamics. This is calcium-dependent and PIP2-regulated.
      action: ACCEPT
      reason: >-
        This is the primary and defining molecular function of CAPG. The original
        characterization (PMID:1322908) and all subsequent studies confirm CAPG
        as a barbed-end capping protein. This is the most important functional
        annotation for this gene.
      supported_by:
        - reference_id: PMID:1322908
          supporting_text: >-
            Macrophage capping protein (MCP) is a Ca(2+)-sensitive protein which reversibly
            blocks the barbed ends of actin filaments
        - reference_id: file:human/CAPG/CAPG-deep-research-falcon.md
          supporting_text: >-
            Functions primarily as an actin "barbed-end" capping protein (reversibly
            blocks barbed ends)
  - term:
      id: GO:0001726
      label: ruffle
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        CAPG localizes to membrane ruffles in activated macrophages. This is consistent
        with its role in regulating actin dynamics at the leading edge of motile cells.
      action: ACCEPT
      reason: >-
        UniProt subcellular location data indicates CAPG localization to ruffles,
        which is consistent with its function as an actin-capping protein at the
        leading edge of activated macrophages.
      supported_by:
        - reference_id: file:human/CAPG/CAPG-uniprot.txt
          supporting_text: >-
            Cell projection, ruffle... In activated macrophages, concentrated in the
            ruffles of the leading lamellipodia
  - term:
      id: GO:0003779
      label: actin binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        CAPG binds actin through its gelsolin-like domains. This is the parent term
        of the more specific actin filament binding annotation.
      action: ACCEPT
      reason: >-
        Actin binding is a fundamental property of CAPG. While more specific terms
        (actin filament binding, barbed-end capping) are preferable, this general
        annotation from UniProt keyword mapping is not incorrect.
      supported_by:
        - reference_id: PMID:1322908
          supporting_text: >-
            Sequence comparison with other actin-binding protein sequences indicates
            that MCP is a member of the gelsolin/villin family of barbed end blocking
            proteins
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        CAPG localizes to the nucleus via importin-beta/NTF2/Ran-dependent import.
        Nuclear localization has been observed in fibroblasts and is supported by
        multiple studies demonstrating dynamic nucleo-cytoplasmic shuttling.
      action: ACCEPT
      reason: >-
        Nuclear localization of CAPG is well-documented. PMID:18266911 demonstrates
        CAPG nuclear import via NTF2/Ran, and nuclear CAPG may have functional roles
        in invasion and transcriptional regulation.
      supported_by:
        - reference_id: PMID:18266911
          supporting_text: >-
            NTF2 and Ran control nuclear import of the filamentous actin capping protein
            CapG... we show that CapG binds to nucleoporin62
        - reference_id: file:human/CAPG/CAPG-deep-research-falcon.md
          supporting_text: >-
            Localizes to cytoplasm and nucleus with dynamic nucleo-cytoplasmic distribution;
            nuclear import can be energy/importin-beta dependent
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        CAPG is abundant in the cytoplasm of macrophages, where it represents 0.9-1%
        of total cytoplasmic protein. Cytoplasmic localization is the primary site
        of CAPG function.
      action: ACCEPT
      reason: >-
        Cytoplasmic localization is well-established for CAPG. The original paper
        (PMID:1322908) notes its abundance in macrophage cytoplasm, and UniProt
        confirms cytoplasmic localization.
      supported_by:
        - reference_id: PMID:1322908
          supporting_text: >-
            it was abundant, representing 0.9-1% of the total cytoplasmic protein
        - reference_id: file:human/CAPG/CAPG-uniprot.txt
          supporting_text: >-
            In macrophages, may be predominantly cytoplasmic
  - term:
      id: GO:0030027
      label: lamellipodium
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        CAPG localizes to lamellipodia in activated macrophages, consistent with its
        role in regulating actin dynamics at the leading edge.
      action: ACCEPT
      reason: >-
        Lamellipodium localization is directly relevant to CAPG's function as an
        actin-capping protein. It regulates barbed-end dynamics at the cortex and
        leading edge.
      supported_by:
        - reference_id: file:human/CAPG/CAPG-uniprot.txt
          supporting_text: >-
            Cell projection, lamellipodium... In activated macrophages, concentrated
            in the ruffles of the leading lamellipodia
  - term:
      id: GO:0042470
      label: melanosome
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        CAPG was identified in melanosomes via proteomic analysis of melanoma cells.
        This is likely a proteomics-based finding rather than a core functional localization.
      action: KEEP_AS_NON_CORE
      reason: >-
        Melanosome localization was detected in large-scale proteomic analysis (PMID:17081065)
        but is not a core functional site for CAPG. This represents detection in a
        specific cell type (melanoma) rather than a defining localization.
      supported_by:
        - reference_id: file:human/CAPG/CAPG-uniprot.txt
          supporting_text: >-
            Melanosome {ECO:0000269|PubMed:17081065}
  - term:
      id: GO:0051015
      label: actin filament binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: >-
        Duplicate annotation of actin filament binding from InterPro mapping. The
        gelsolin domains in CAPG directly bind actin filaments.
      action: ACCEPT
      reason: >-
        Actin filament binding is a core function of CAPG. This InterPro-based annotation
        is redundant with the IBA annotation but is correct.
      supported_by:
        - reference_id: PMID:1322908
          supporting_text: >-
            MCP is a member of the gelsolin/villin family of barbed end blocking proteins
  - term:
      id: GO:0051693
      label: actin filament capping
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        Actin filament capping is the general term for CAPG's activity. The more
        specific term GO:0051016 (barbed-end actin filament capping) is preferable,
        but this annotation is not incorrect.
      action: ACCEPT
      reason: >-
        CAPG is an actin filament capping protein. While the more specific barbed-end
        capping term is preferable, this general annotation from UniProt keyword
        mapping is accurate.
      supported_by:
        - reference_id: PMID:1322908
          supporting_text: >-
            Macrophage capping protein (MCP) is a Ca(2+)-sensitive protein which reversibly
            blocks the barbed ends of actin filaments
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25416956
    review:
      summary: >-
        Generic protein binding annotation from high-throughput interactome mapping.
        This term is too vague to be informative about CAPG's actual protein interactions.
      action: REMOVE
      reason: >-
        "Protein binding" is uninformative. CAPG has specific protein interactions
        (e.g., NUP62, NTF2, RAN, actin) that should be annotated with more specific
        terms. Generic protein binding annotations from high-throughput screens do
        not add functional insight.
      supported_by:
        - reference_id: file:human/CAPG/CAPG-deep-research-falcon.md
          supporting_text: >-
            CAPG interacts with RAVER1 and may be recruited to adhesion complexes
        - reference_id: PMID:25416956
          supporting_text: A proteome-scale map of the human interactome 
            network.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32814053
    review:
      summary: >-
        Generic protein binding annotation from interactome mapping study related
        to neurodegenerative disease. Too vague to be informative.
      action: REMOVE
      reason: >-
        "Protein binding" provides no functional insight. More specific terms should
        be used to describe CAPG's protein interactions.
      supported_by:
        - reference_id: file:human/CAPG/CAPG-uniprot.txt
          supporting_text: >-
            Interacts with NUP62... Interacts with NUTF2 and RAN; involved in CAPG
            nuclear import
        - 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: >-
        Generic protein binding annotation from dual proteome interactome study.
        Too vague to be informative.
      action: REMOVE
      reason: >-
        "Protein binding" is uninformative. CAPG has specific, characterized protein
        interactions that warrant more specific annotation.
      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:0005654
      label: nucleoplasm
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: >-
        CAPG localizes to the nucleoplasm as part of its nucleo-cytoplasmic shuttling.
        Immunofluorescence data supports nucleoplasm localization.
      action: ACCEPT
      reason: >-
        Nucleoplasm localization is supported by immunofluorescence studies and is
        consistent with CAPG's nuclear import via NTF2/Ran.
      supported_by:
        - reference_id: PMID:18266911
          supporting_text: >-
            NTF2 and Ran control nuclear import of the filamentous actin capping protein
            CapG
  - term:
      id: GO:0045296
      label: cadherin binding
    evidence_type: HDA
    original_reference_id: PMID:25468996
    review:
      summary: >-
        CAPG was identified as an E-cadherin interactor in quantitative proteomic
        analysis. This may relate to CAPG's role at cell-cell adhesion sites.
      action: KEEP_AS_NON_CORE
      reason: >-
        Cadherin binding was identified in a proteomics study of the E-cadherin
        interactome. While potentially relevant to CAPG's role at adhesion sites,
        this is not a core function of the protein.
      supported_by:
        - reference_id: file:human/CAPG/CAPG-deep-research-falcon.md
          supporting_text: >-
            CAPG interacts with RAVER1 and may be recruited to adhesion complexes
        - reference_id: PMID:25468996
          supporting_text: E-cadherin interactome complexity and robustness 
            resolved by quantitative proteomics.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:25468996
    review:
      summary: >-
        Cytoplasmic localization confirmed in the E-cadherin interactome study.
        Consistent with other evidence for cytoplasmic CAPG.
      action: ACCEPT
      reason: >-
        Cytoplasmic localization is well-established for CAPG. This IDA annotation
        provides additional support.
      supported_by:
        - reference_id: PMID:1322908
          supporting_text: >-
            representing 0.9-1% of the total cytoplasmic protein
        - reference_id: PMID:25468996
          supporting_text: E-cadherin interactome complexity and robustness 
            resolved by quantitative proteomics.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:18266911
    review:
      summary: >-
        Generic protein binding annotation from the nuclear import study. The
        specific interactions (NUP62, NTF2, RAN) are more informative.
      action: REMOVE
      reason: >-
        "Protein binding" is too vague. This paper (PMID:18266911) characterizes
        specific interactions with NUP62, NTF2, and RAN that should be annotated
        with more specific terms rather than generic protein binding.
      supported_by:
        - reference_id: PMID:18266911
          supporting_text: >-
            CapG binds to nucleoporin62... CapG interacts with NTF2, associates with
            Ran
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:18266911
    review:
      summary: >-
        Nuclear localization demonstrated via nuclear import studies showing CAPG
        uses NTF2/Ran-dependent pathway.
      action: ACCEPT
      reason: >-
        PMID:18266911 directly demonstrates CAPG nuclear import and characterizes
        the mechanism involving NTF2, Ran, and NUP62.
      supported_by:
        - reference_id: PMID:18266911
          supporting_text: >-
            NTF2 and Ran control nuclear import of the filamentous actin capping protein
            CapG... a ubiquitously expressed protein shuttles to the nucleus through
            direct association with NTF2 and Ran
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:18266911
    review:
      summary: >-
        Cytoplasmic localization shown in the context of nucleo-cytoplasmic shuttling
        studies.
      action: ACCEPT
      reason: >-
        Cytoplasmic localization is well-supported and part of CAPG's dynamic
        nucleo-cytoplasmic distribution.
      supported_by:
        - reference_id: PMID:18266911
          supporting_text: >-
            nuclear import of the filamentous actin capping protein CapG
  - term:
      id: GO:0019904
      label: protein domain specific binding
    evidence_type: IPI
    original_reference_id: PMID:18266911
    review:
      summary: >-
        CAPG interacts with specific protein domains during nuclear import. The
        NTF2-Ran complex interaction is domain-specific.
      action: KEEP_AS_NON_CORE
      reason: >-
        While the nuclear import paper shows domain-specific interactions, this is
        not a core function of CAPG. The annotation reflects the mechanism of
        nuclear import rather than CAPG's primary actin-related functions.
      supported_by:
        - reference_id: PMID:18266911
          supporting_text: >-
            CapG interacts with NTF2, associates with Ran and is furthermore able
            to
            bind the NTF2-Ran complex
  - term:
      id: GO:0044877
      label: protein-containing complex binding
    evidence_type: IDA
    original_reference_id: PMID:18266911
    review:
      summary: >-
        CAPG binds the NTF2-Ran complex for nuclear import. This represents binding
        to a protein-containing complex.
      action: KEEP_AS_NON_CORE
      reason: >-
        The NTF2-Ran complex binding is relevant to nuclear import but not CAPG's
        core actin-capping function. Keep as non-core to reflect this secondary
        functional aspect.
      supported_by:
        - reference_id: PMID:18266911
          supporting_text: >-
            CapG interacts with NTF2, associates with Ran and is furthermore able
            to
            bind the NTF2-Ran complex
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: IDA
    original_reference_id: PMID:18938132
    review:
      summary: >-
        CAPG localizes to the nucleoplasm as demonstrated in the nucleolar localization
        study.
      action: ACCEPT
      reason: >-
        Nucleoplasm localization is confirmed by IDA evidence in the context of
        studying CAPG's nucleolar localization.
      supported_by:
        - reference_id: PMID:18938132
          supporting_text: >-
            the actin capping protein CapG localizes in the nucleolus of cultured
            cells
  - term:
      id: GO:0005730
      label: nucleolus
    evidence_type: IDA
    original_reference_id: PMID:18938132
    review:
      summary: >-
        CAPG localizes to the nucleolus in an active, ATP-dependent process that
        requires RNA Polymerase I transcription. This localization may be relevant
        to actin-based regulation of ribosomal gene transcription.
      action: ACCEPT
      reason: >-
        PMID:18938132 directly demonstrates CAPG nucleolar localization and
        characterizes it as ATP-dependent and linked to active RNA Pol I transcription.
      supported_by:
        - reference_id: PMID:18938132
          supporting_text: >-
            we show that the actin capping protein CapG localizes in the nucleolus
            of
            cultured cells. CapG transport to the nucleolus is an active and ATP-dependent
            process. Association of CapG with the nucleolus requires active RNA Polymerase
            I transcription
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:18938132
    review:
      summary: >-
        Cytoplasmic localization observed in nucleolar localization studies, consistent
        with nucleo-cytoplasmic shuttling.
      action: ACCEPT
      reason: >-
        Cytoplasmic localization is consistently observed and is part of CAPG's
        dynamic distribution.
      supported_by:
        - reference_id: PMID:18938132
          supporting_text: >-
            CapG transport to the nucleolus is an active and ATP-dependent process
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:19166812
    review:
      summary: >-
        Cytoplasmic localization observed in cell cycle localization studies.
      action: ACCEPT
      reason: >-
        Consistent with other evidence for cytoplasmic CAPG.
      supported_by:
        - reference_id: PMID:19166812
          supporting_text: >-
            Fluorescence microscopy of endogenous CapG and EGFP-tagged CapG revealed
            CapG localization at the mother centriole in interphase
  - term:
      id: GO:0005814
      label: centriole
    evidence_type: IDA
    original_reference_id: PMID:19166812
    review:
      summary: >-
        CAPG localizes to the mother centriole during interphase. This localization
        suggests a role in cross-talk between actin and microtubule-based structures.
      action: KEEP_AS_NON_CORE
      reason: >-
        Centriole localization during interphase is demonstrated by fluorescence
        microscopy but represents a cell cycle-specific localization rather than
        CAPG's core functional site.
      supported_by:
        - reference_id: PMID:19166812
          supporting_text: >-
            Fluorescence microscopy of endogenous CapG and EGFP-tagged CapG revealed
            CapG localization at the mother centriole in interphase
  - term:
      id: GO:0072686
      label: mitotic spindle
    evidence_type: IDA
    original_reference_id: PMID:19166812
    review:
      summary: >-
        CAPG localizes to the mitotic spindle during mitosis. This suggests involvement
        in actin-microtubule cross-talk during cell division.
      action: KEEP_AS_NON_CORE
      reason: >-
        Mitotic spindle localization is cell cycle-specific and suggests a role in
        cross-talk between actin and microtubule cytoskeletons, but this is not
        CAPG's core function.
      supported_by:
        - reference_id: PMID:19166812
          supporting_text: >-
            CapG localization at the mother centriole in interphase, the mitotic spindle
            in mitosis and the midbody ring in abscission
  - term:
      id: GO:0090543
      label: Flemming body
    evidence_type: IDA
    original_reference_id: PMID:19166812
    review:
      summary: >-
        CAPG localizes to the midbody ring (Flemming body) during abscission. NUP62,
        an interaction partner, colocalizes with CAPG at this site.
      action: KEEP_AS_NON_CORE
      reason: >-
        Flemming body localization during abscission is cell cycle-specific. This
        is not CAPG's core function but may reflect a role in cytokinesis.
      supported_by:
        - reference_id: PMID:19166812
          supporting_text: >-
            the midbody ring in abscission. Surprisingly, nucleoporin Nup62, an interaction
            partner of CapG, also localized to the midbody ring at the end of abscission
            and colocalized with CapG
  - term:
      id: GO:0070062
      label: extracellular exosome
    evidence_type: HDA
    original_reference_id: PMID:23533145
    review:
      summary: >-
        CAPG detected in prostatic secretion exosomes by proteomics. This is likely
        a passive inclusion rather than a core functional localization.
      action: KEEP_AS_NON_CORE
      reason: >-
        Exosome detection is from high-throughput proteomic analysis. Many cytoplasmic
        proteins are detected in exosomes without having specific exosome-related
        functions.
      supported_by:
        - reference_id: PMID:23533145
          supporting_text: 2013 Apr 23. In-depth proteomic analyses of exosomes 
            isolated from expressed prostatic secretions in urine.
  - term:
      id: GO:0070062
      label: extracellular exosome
    evidence_type: HDA
    original_reference_id: PMID:19056867
    review:
      summary: >-
        CAPG detected in urinary exosomes by proteomics.
      action: KEEP_AS_NON_CORE
      reason: >-
        Exosome detection is from proteomics; not a core functional localization.
      supported_by:
        - reference_id: PMID:19056867
          supporting_text: 2008 Dec 3. Large-scale proteomics and 
            phosphoproteomics of urinary exosomes.
  - term:
      id: GO:0070062
      label: extracellular exosome
    evidence_type: HDA
    original_reference_id: PMID:20458337
    review:
      summary: >-
        CAPG detected in B-cell exosomes by proteomics in MHC class II-associated
        protein study.
      action: KEEP_AS_NON_CORE
      reason: >-
        Exosome detection from proteomics; not a core functional localization.
      supported_by:
        - reference_id: PMID:20458337
          supporting_text: 2010 May 11. MHC class II-associated proteins in 
            B-cell exosomes and potential functional implications for exosome 
            biogenesis.
  - term:
      id: GO:0065003
      label: protein-containing complex assembly
    evidence_type: NAS
    original_reference_id: PMID:1322908
    review:
      summary: >-
        CAPG may participate in F-actin capping protein complex assembly. This
        relates to its role in actin filament dynamics.
      action: ACCEPT
      reason: >-
        CAPG's function in capping actin filaments involves assembly of functional
        complexes with actin. The annotation is consistent with its role in actin
        cytoskeleton organization.
      supported_by:
        - reference_id: PMID:1322908
          supporting_text: >-
            MCP is a member of the gelsolin/villin family of barbed end blocking proteins
  - term:
      id: GO:0051016
      label: barbed-end actin filament capping
    evidence_type: TAS
    original_reference_id: PMID:1322908
    review:
      summary: >-
        The original characterization paper directly demonstrates CAPG's barbed-end
        capping activity. This is the defining molecular function of the protein.
      action: ACCEPT
      reason: >-
        PMID:1322908 is the primary reference establishing CAPG as a barbed-end
        capping protein. The TAS annotation is well-supported by the original
        biochemical characterization.
      supported_by:
        - reference_id: PMID:1322908
          supporting_text: >-
            Macrophage capping protein (MCP) is a Ca(2+)-sensitive protein which reversibly
            blocks the barbed ends of actin filaments... ability to block monomer
            exchange
            at the barbed end of actin filaments
  - term:
      id: GO:0008290
      label: F-actin capping protein complex
    evidence_type: TAS
    original_reference_id: PMID:1322908
    review:
      summary: >-
        CAPG is part of the F-actin capping protein complex, forming functional
        complexes with actin filaments at their barbed ends.
      action: ACCEPT
      reason: >-
        CAPG caps F-actin at barbed ends, making it part of the F-actin capping
        machinery. This cellular component annotation is appropriate.
      supported_by:
        - reference_id: PMID:1322908
          supporting_text: >-
            Macrophage capping protein (MCP) is a Ca(2+)-sensitive protein which reversibly
            blocks the barbed ends of actin filaments but does not sever preformed
            actin filaments
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with
      GO terms.
    findings: []
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings: []
  - 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, accompanied by conservative changes to GO 
      terms applied by UniProt.
    findings: []
  - id: GO_REF:0000052
    title: Gene Ontology annotation based on curation of immunofluorescence data
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods.
    findings: []
  - id: PMID:1322908
    title: Molecular cloning of human macrophage capping protein cDNA. A unique 
      member of the gelsolin/villin family expressed primarily in macrophages.
    findings:
      - statement: CAPG reversibly blocks barbed ends of actin filaments
      - statement: CAPG does NOT sever preformed actin filaments
      - statement: Ca2+-sensitive activity
      - statement: Member of gelsolin/villin family
      - statement: Abundant in macrophages (0.9-1% of cytoplasmic protein)
  - id: PMID:18266911
    title: 'A new role for nuclear transport factor 2 and Ran: nuclear import of CapG.'
    findings:
      - statement: CAPG nuclear import via NTF2/Ran pathway
      - statement: CAPG binds NUP62
      - statement: CAPG interacts with NTF2 and RAN
  - id: PMID:18938132
    title: The F-actin filament capping protein CapG is a bona fide nucleolar 
      protein.
    findings:
      - statement: CAPG localizes to nucleolus
      - statement: ATP-dependent nucleolar transport
      - statement: Requires active RNA Pol I transcription
  - id: PMID:19056867
    title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
    findings: []
  - id: PMID:19166812
    title: The actin-capping protein CapG localizes to microtubule-dependent 
      organelles during the cell cycle.
    findings:
      - statement: CAPG at mother centriole in interphase
      - statement: CAPG at mitotic spindle in mitosis
      - statement: CAPG at midbody ring in abscission
      - statement: NUP62 colocalizes with CAPG at midbody
  - id: PMID:20458337
    title: MHC class II-associated proteins in B-cell exosomes and potential 
      functional implications for exosome biogenesis.
    findings: []
  - id: PMID:23533145
    title: In-depth proteomic analyses of exosomes isolated from expressed 
      prostatic secretions in urine.
    findings: []
  - id: PMID:25416956
    title: A proteome-scale map of the human interactome network.
    findings: []
  - id: PMID:25468996
    title: E-cadherin interactome complexity and robustness resolved by 
      quantitative proteomics.
    findings:
      - statement: CAPG identified as E-cadherin interactor
  - id: PMID:32814053
    title: Interactome Mapping Provides a Network of Neurodegenerative Disease 
      Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
    findings: []
  - id: PMID:33961781
    title: Dual proteome-scale networks reveal cell-specific remodeling of the 
      human interactome.
    findings: []
  - id: file:human/CAPG/CAPG-deep-research-falcon.md
    title: Deep research on CAPG function
    findings:
      - statement: CAPG is barbed-end capping protein (not severing)
      - statement: Regulated by Ca2+ and PIP2
      - statement: Redox-sensitive via C282/C290
      - statement: Nucleo-cytoplasmic shuttling
      - statement: Overexpressed in cancers
core_functions:
  - description: >-
      CAPG reversibly blocks barbed ends of actin filaments in a calcium-sensitive
      manner. This is the defining molecular function of the protein, established
      in the original characterization (PMID:1322908) and confirmed in all subsequent
      studies. CAPG notably does NOT sever actin filaments, distinguishing it from
      gelsolin.
    molecular_function:
      id: GO:0051015
      label: actin filament binding
    locations:
      - id: GO:0015629
        label: actin cytoskeleton
      - id: GO:0030027
        label: lamellipodium
      - id: GO:0001726
        label: ruffle
    directly_involved_in:
      - id: GO:0030031
        label: cell projection assembly
      - id: GO:0008154
        label: actin polymerization or depolymerization
    supported_by:
      - reference_id: PMID:1322908
        supporting_text: >-
          Macrophage capping protein (MCP) is a Ca(2+)-sensitive protein which reversibly
          blocks the barbed ends of actin filaments but does not sever preformed actin
          filaments
proposed_new_terms: []
suggested_questions:
  - question: What is the functional significance of CAPG nuclear localization?
  - question: Does CAPG have nuclear actin-related functions or transcriptional 
      roles?
  - question: What is the relationship between CAPG redox sensitivity and cancer
      progression?
suggested_experiments:
  - description: Characterize the role of CAPG in nuclear actin regulation
    hypothesis: CAPG regulates nuclear actin dynamics for gene expression or 
      chromatin organization
    experiment_type: biochemical assay
  - description: Investigate CAPG's role in nucleolar function and ribosomal 
      gene transcription
    hypothesis: CAPG nucleolar localization is functionally linked to rRNA 
      transcription
    experiment_type: gene expression
  - description: Determine the functional significance of CAPG-RAVER1 
      interaction
    hypothesis: CAPG-RAVER1 interaction at adhesion complexes regulates cell 
      migration
    experiment_type: protein interaction