CAPG

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0015629 actin cytoskeleton	IBA GO_REF:0000033	ACCEPT	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. 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. Supporting Evidence: PMID:1322908 Macrophage capping protein (MCP) is a Ca(2+)-sensitive protein which reversibly blocks the barbed ends of actin filaments file:human/CAPG/CAPG-deep-research-falcon.md CAPG is the human macrophage-capping protein (also called gCap39) belonging to the gelsolin/villin superfamily
GO:0051015 actin filament binding	IBA GO_REF:0000033	ACCEPT	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. 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). Supporting Evidence: PMID:1322908 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 file:human/CAPG/CAPG-deep-research-falcon.md Binds actin monomers and can influence nucleation/polymerization kinetics; lower actin-binding affinity than full-length gelsolin
GO:0008154 actin polymerization or depolymerization	IBA GO_REF:0000033	ACCEPT	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. 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. Supporting Evidence: PMID:1322908 ability to block monomer exchange at the barbed end of actin filaments file:human/CAPG/CAPG-deep-research-falcon.md CAPG caps actin filament barbed ends to tune filament elongation
GO:0051014 actin filament severing	IBA GO_REF:0000033	REMOVE	Summary: Direct characterization distinguishes CAPG barbed-end capping from actin-filament severing. Reason: PTHR11977 places severing at ancestral node PTN000240164. Human CAPG recombinant protein was assayed as a calcium-sensitive capping protein and explicitly did not sever preformed filaments (PMID:1322908). This target-specific functional distinction challenges retention along the CAPG branch. The existing OpenScientist report agrees and acknowledges that homology to the gelsolin N-terminal half is insufficient; domain count alone would not establish loss because other three-domain gelsolin fragments can sever. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000240164 · PTN000240164 SUPPORTS SOURCE BUT NOT TARGET Severing is supported in the ancestral gelsolin family, whereas direct CAPG assays distinguish capping from severing. Supporting Evidence: PMID:1322908 blocks the barbed ends of actin filaments but does not sever preformed actin filaments. file:human/CAPG/CAPG-hypotheses/function-hypothesis-go-0051014/openscientist.md domain homology to gelsolin's N-terminal half is not sufficient to confer severing
GO:0005546 phosphatidylinositol-4,5-bisphosphate binding	IBA GO_REF:0000033	ACCEPT	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. 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. Supporting Evidence: file:human/CAPG/CAPG-deep-research-falcon.md Activity is Ca2+-sensitive and regulated by polyphosphoinositides (PIP2) which can antagonize capping; regulation is rapid and reversible file:human/CAPG/CAPG-deep-research-falcon.md Ca2+ promotes active conformations of the gelsolin-like domains; PIP2 binding antagonizes capping, allowing leading-edge control
GO:0007417 central nervous system development	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Retain the inherited developmental context as non-core relative to CAPG actin capping. Reason: PTHR11977 places central nervous system development at PTN008334354, with rat and zebrafish experimental descendants. No CAPG-specific loss of this inherited developmental role was established. The annotation is retained as a phylogenetic inference; generic involvement of actin in development is not itself target-specific experimental evidence.
GO:0030031 cell projection assembly	IBA GO_REF:0000033	ACCEPT	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. 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. Supporting Evidence: PMID:1322908 MCP may play an important role in macrophage function. file:human/CAPG/CAPG-uniprot.txt In activated macrophages, concentrated in the ruffles of the leading lamellipodia
GO:0051016 barbed-end actin filament capping	IBA GO_REF:0000033	ACCEPT	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. 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. Supporting Evidence: PMID:1322908 Macrophage capping protein (MCP) is a Ca(2+)-sensitive protein which reversibly blocks the barbed ends of actin filaments file:human/CAPG/CAPG-deep-research-falcon.md Functions primarily as an actin "barbed-end" capping protein (reversibly blocks barbed ends)
GO:0001726 ruffle	IEA GO_REF:0000044	ACCEPT	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. 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. Supporting Evidence: file:human/CAPG/CAPG-uniprot.txt In activated macrophages, concentrated in the ruffles of the leading lamellipodia.
GO:0003779 actin binding	IEA GO_REF:0000043	ACCEPT	Summary: CAPG binds actin through its gelsolin-like domains. This is the parent term of the more specific actin filament binding annotation. 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. Supporting Evidence: PMID:1322908 Sequence comparison with other actin-binding protein sequences indicates that MCP is a member of the gelsolin/villin family of barbed end blocking proteins
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	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. 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. Supporting Evidence: PMID:18266911 NTF2 and Ran control nuclear import of the filamentous actin capping protein CapG. PMID:18266911 Thus, a ubiquitously expressed protein shuttles to the nucleus through direct association with NTF2 and Ran.
GO:0005737 cytoplasm	IEA GO_REF:0000120	ACCEPT	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. Reason: Cytoplasmic localization is well-established for CAPG. The original paper (PMID:1322908) notes its abundance in macrophage cytoplasm, and UniProt confirms cytoplasmic localization. Supporting Evidence: PMID:1322908 it was abundant, representing 0.9-1% of the total cytoplasmic protein file:human/CAPG/CAPG-uniprot.txt In macrophages, may be predominantly cytoplasmic
GO:0030027 lamellipodium	IEA GO_REF:0000044	ACCEPT	Summary: CAPG localizes to lamellipodia in activated macrophages, consistent with its role in regulating actin dynamics at the leading edge. 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. Supporting Evidence: file:human/CAPG/CAPG-uniprot.txt In activated macrophages, concentrated in the ruffles of the leading lamellipodia.
GO:0042470 melanosome	IEA GO_REF:0000044	KEEP AS NON CORE	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. 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. Supporting Evidence: file:human/CAPG/CAPG-uniprot.txt Melanosome {ECO:0000269\|PubMed:17081065}
GO:0051015 actin filament binding	IEA GO_REF:0000002	ACCEPT	Summary: Duplicate annotation of actin filament binding from InterPro mapping. The gelsolin domains in CAPG directly bind actin filaments. Reason: Actin filament binding is a core function of CAPG. This InterPro-based annotation is redundant with the IBA annotation but is correct. Supporting Evidence: PMID:1322908 MCP is a member of the gelsolin/villin family of barbed end blocking proteins
GO:0051693 actin filament capping	IEA GO_REF:0000043	ACCEPT	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. 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. Supporting Evidence: PMID:1322908 Macrophage capping protein (MCP) is a Ca(2+)-sensitive protein which reversibly blocks the barbed ends of actin filaments
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	REMOVE	Summary: Generic protein binding annotation from high-throughput interactome mapping. This term is too vague to be informative about CAPG's actual protein interactions. 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. Supporting Evidence: file:human/CAPG/CAPG-deep-research-falcon.md CAPG interacts with RAVER1 and may be recruited to adhesion complexes PMID:25416956 A proteome-scale map of the human interactome network.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding annotation from interactome mapping study related to neurodegenerative disease. Too vague to be informative. Reason: "Protein binding" provides no functional insight. More specific terms should be used to describe CAPG's protein interactions. Supporting Evidence: file:human/CAPG/CAPG-uniprot.txt Interacts with NUTF2 and RAN; involved in CAPG nuclear import PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Generic protein binding annotation from dual proteome interactome study. Too vague to be informative. Reason: "Protein binding" is uninformative. CAPG has specific, characterized protein interactions that warrant more specific annotation. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005654 nucleoplasm	IDA GO_REF:0000052	ACCEPT	Summary: CAPG localizes to the nucleoplasm as part of its nucleo-cytoplasmic shuttling. Immunofluorescence data supports nucleoplasm localization. Reason: Nucleoplasm localization is supported by immunofluorescence studies and is consistent with CAPG's nuclear import via NTF2/Ran. Supporting Evidence: PMID:18266911 NTF2 and Ran control nuclear import of the filamentous actin capping protein CapG
GO:0045296 cadherin binding	HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by...	KEEP AS NON CORE	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. 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. Supporting Evidence: file:human/CAPG/CAPG-deep-research-falcon.md CAPG interacts with RAVER1 and may be recruited to adhesion complexes PMID:25468996 E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
GO:0005737 cytoplasm	IDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by...	ACCEPT	Summary: Cytoplasmic localization confirmed in the E-cadherin interactome study. Consistent with other evidence for cytoplasmic CAPG. Reason: Cytoplasmic localization is well-established for CAPG. This IDA annotation provides additional support. Supporting Evidence: PMID:1322908 representing 0.9-1% of the total cytoplasmic protein PMID:25468996 E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
GO:0005515 protein binding	IPI PMID:18266911 A new role for nuclear transport factor 2 and Ran: nuclear i...	MODIFY	Summary: CAPG associates with the small GTPase Ran in the nuclear import machinery. Reason: The primary study identifies Ran as an interaction partner and reports binding to the NTF2-Ran complex. Small GTPase binding describes the Ran interaction more informatively than generic protein binding without asserting GTPase activity for CAPG. Proposed replacements: small GTPase binding Supporting Evidence: PMID:18266911 CapG interacts with NTF2, associates with Ran and is furthermore able to bind the NTF2-Ran complex.
GO:0005634 nucleus	IDA PMID:18266911 A new role for nuclear transport factor 2 and Ran: nuclear i...	ACCEPT	Summary: Nuclear localization demonstrated via nuclear import studies showing CAPG uses NTF2/Ran-dependent pathway. Reason: PMID:18266911 directly demonstrates CAPG nuclear import and characterizes the mechanism involving NTF2, Ran, and NUP62. Supporting Evidence: PMID:18266911 NTF2 and Ran control nuclear import of the filamentous actin capping protein CapG.
GO:0005737 cytoplasm	IDA PMID:18266911 A new role for nuclear transport factor 2 and Ran: nuclear i...	ACCEPT	Summary: Cytoplasmic localization shown in the context of nucleo-cytoplasmic shuttling studies. Reason: Cytoplasmic localization is well-supported and part of CAPG's dynamic nucleo-cytoplasmic distribution. Supporting Evidence: PMID:18266911 nuclear import of the filamentous actin capping protein CapG
GO:0019904 protein domain specific binding	IPI PMID:18266911 A new role for nuclear transport factor 2 and Ran: nuclear i...	KEEP AS NON CORE	Summary: CAPG interacts with specific protein domains during nuclear import. The NTF2-Ran complex interaction is domain-specific. 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. Supporting Evidence: PMID:18266911 CapG interacts with NTF2, associates with Ran and is furthermore able to bind the NTF2-Ran complex
GO:0044877 protein-containing complex binding	IDA PMID:18266911 A new role for nuclear transport factor 2 and Ran: nuclear i...	KEEP AS NON CORE	Summary: CAPG binds the NTF2-Ran complex for nuclear import. This represents binding to a protein-containing complex. 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. Supporting Evidence: PMID:18266911 CapG interacts with NTF2, associates with Ran and is furthermore able to bind the NTF2-Ran complex
GO:0005654 nucleoplasm	IDA PMID:18938132 The F-actin filament capping protein CapG is a bona fide nuc...	ACCEPT	Summary: CAPG localizes to the nucleoplasm as demonstrated in the nucleolar localization study. Reason: Nucleoplasm localization is confirmed by IDA evidence in the context of studying CAPG's nucleolar localization. Supporting Evidence: PMID:18938132 the actin capping protein CapG localizes in the nucleolus of cultured cells
GO:0005730 nucleolus	IDA PMID:18938132 The F-actin filament capping protein CapG is a bona fide nuc...	ACCEPT	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. Reason: PMID:18938132 directly demonstrates CAPG nucleolar localization and characterizes it as ATP-dependent and linked to active RNA Pol I transcription. Supporting Evidence: PMID:18938132 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
GO:0005737 cytoplasm	IDA PMID:18938132 The F-actin filament capping protein CapG is a bona fide nuc...	ACCEPT	Summary: Cytoplasmic localization observed in nucleolar localization studies, consistent with nucleo-cytoplasmic shuttling. Reason: Cytoplasmic localization is consistently observed and is part of CAPG's dynamic distribution. Supporting Evidence: PMID:18938132 CapG transport to the nucleolus is an active and ATP-dependent process
GO:0005737 cytoplasm	IDA PMID:19166812 The actin-capping protein CapG localizes to microtubule-depe...	ACCEPT	Summary: Cytoplasmic localization observed in cell cycle localization studies. Reason: Consistent with other evidence for cytoplasmic CAPG. Supporting Evidence: PMID:19166812 Fluorescence microscopy of endogenous CapG and EGFP-tagged CapG revealed CapG localization at the mother centriole in interphase
GO:0005814 centriole	IDA PMID:19166812 The actin-capping protein CapG localizes to microtubule-depe...	KEEP AS NON CORE	Summary: CAPG localizes to the mother centriole during interphase. This localization suggests a role in cross-talk between actin and microtubule-based structures. Reason: Centriole localization during interphase is demonstrated by fluorescence microscopy but represents a cell cycle-specific localization rather than CAPG's core functional site. Supporting Evidence: PMID:19166812 Fluorescence microscopy of endogenous CapG and EGFP-tagged CapG revealed CapG localization at the mother centriole in interphase
GO:0072686 mitotic spindle	IDA PMID:19166812 The actin-capping protein CapG localizes to microtubule-depe...	KEEP AS NON CORE	Summary: CAPG localizes to the mitotic spindle during mitosis. This suggests involvement in actin-microtubule cross-talk during cell division. 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. Supporting Evidence: PMID:19166812 CapG localization at the mother centriole in interphase, the mitotic spindle in mitosis and the midbody ring in abscission
GO:0090543 Flemming body	IDA PMID:19166812 The actin-capping protein CapG localizes to microtubule-depe...	KEEP AS NON CORE	Summary: CAPG localizes to the midbody ring (Flemming body) during abscission. NUP62, an interaction partner, colocalizes with CAPG at this site. Reason: Flemming body localization during abscission is cell cycle-specific. This is not CAPG's core function but may reflect a role in cytokinesis. Supporting Evidence: PMID:19166812 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
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	KEEP AS NON CORE	Summary: CAPG detected in prostatic secretion exosomes by proteomics. This is likely a passive inclusion rather than a core functional localization. Reason: Exosome detection is from high-throughput proteomic analysis. Many cytoplasmic proteins are detected in exosomes without having specific exosome-related functions. Supporting Evidence: PMID:23533145 2013 Apr 23. In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: CAPG detected in urinary exosomes by proteomics. Reason: Exosome detection is from proteomics; not a core functional localization. Supporting Evidence: PMID:19056867 2008 Dec 3. Large-scale proteomics and phosphoproteomics of urinary exosomes.
GO:0070062 extracellular exosome	HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote...	KEEP AS NON CORE	Summary: CAPG detected in B-cell exosomes by proteomics in MHC class II-associated protein study. Reason: Exosome detection from proteomics; not a core functional localization. Supporting Evidence: PMID:20458337 2010 May 11. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
GO:0065003 protein-containing complex assembly	NAS PMID:1322908 Molecular cloning of human macrophage capping protein cDNA. ...	ACCEPT	Summary: CAPG may participate in F-actin capping protein complex assembly. This relates to its role in actin filament dynamics. 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. Supporting Evidence: PMID:1322908 MCP is a member of the gelsolin/villin family of barbed end blocking proteins
GO:0051016 barbed-end actin filament capping	TAS PMID:1322908 Molecular cloning of human macrophage capping protein cDNA. ...	ACCEPT	Summary: The original characterization paper directly demonstrates CAPG's barbed-end capping activity. This is the defining molecular function of the protein. 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. Supporting Evidence: PMID:1322908 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.
GO:0008290 F-actin capping protein complex	TAS PMID:1322908 Molecular cloning of human macrophage capping protein cDNA. ...	REMOVE	Summary: The GO term denotes the alpha/beta heterodimeric capping protein complex, which is distinct from gelsolin-family CapG. Reason: QuickGO defines GO:0008290 as a heterodimer consisting of alpha and beta subunits. PMID:1322908 characterizes the cloned human 38.4-kDa gelsolin-family capping polypeptide; its ability to cap actin does not make it a subunit of the CAPZA/CAPZB-type heterodimer. The original capping activity remains accepted, but this named complex is a different molecular entity. Supporting Evidence: PMID:1322908 The derived amino acid sequence predicts a polypeptide of 38.4 kDa.

Gene Description

Existing Annotations Review

Core Functions

CAPG reversibly blocks barbed ends of actin filaments in a calcium-sensitive manner, controlling filament growth and cell projections. Recombinant human CAPG characterizations distinguish this capping activity from filament severing.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

OpenScientist

📚 Additional Documentation

Notes

CAPG notes

Evidence re-review, 2026-09-20

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