ABI3

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0048858 cell projection morphogenesis	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation from Bilateria node PTN000048907 for cell projection morphogenesis, consistent with ABI3's conserved incorporation as the Abi adaptor subunit of the WAVE regulatory complex (PMID:17101133). Reason: As a conserved subunit of the Abi/WAVE complex (PMID:17101133), ABI3 modulates actin-dependent cell projections; ACCEPT is harmonized with ABI family orthologs at this Bilateria-level IBA node. Supporting Evidence: PMID:17101133 Our results suggest that NESH (Abi-3), like Abi-1 and Abi-2, is a component of the Abi/WAVE complex, but likely plays a different role in the regulation of c-Abl.
GO:0001764 neuron migration	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: IBA annotation inferred from orthologs. ABI family members participate in neuron migration via actin regulation through the WRC. ABI3 is expressed in the brain, particularly in microglia (not neurons primarily), but WRC function in neuron migration is well-established for ABI1/ABI2 orthologs. Reason: Neuron migration is a conserved function of ABI family members through the WRC. However, ABI3 is primarily enriched in microglia rather than neurons in the brain. The IBA inference from orthologs is phylogenetically reasonable but this is not a core function of ABI3 specifically.
GO:0030027 lamellipodium	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for lamellipodium localization from PTN000048906, consistent with ABI3's incorporation into the WAVE regulatory complex and the curator-deferred IDA annotation on PMID:17101133 (abstract-only locally). Reason: Consistent with ABI3's conserved subunit role in the WAVE regulatory complex (PMID:17101133) and supported by curator deference to the full-text IDA annotation on human ABI3 from abstract-only PMID:17101133. Supporting Evidence: PMID:17101133 Immunoprecipitation revealed that NESH (Abi-3) is present in the Abi/WAVE complex
GO:0031209 SCAR complex	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for SCAR/WAVE complex membership. This is very well supported by multiple IDA studies (PMID:17101133, PMID:26428302) and IP-MS data (Moraes et al. 2017). ABI3 is a bona fide component of the WAVE regulatory complex, occupying the Abi subunit position. Reason: Core function of ABI3. Membership in the SCAR/WAVE complex is the defining biochemical role of ABI3. Strongly supported by multiple independent experimental studies. Supporting Evidence: PMID:17101133 Immunoprecipitation revealed that NESH (Abi-3) is present in the Abi/WAVE complex. Our results suggest that NESH (Abi-3), like Abi-1 and Abi-2, is a component of the Abi/WAVE complex PMID:26428302 NESH/Abi-3 was ectopically expressed in NIH3T3 cells, in which Abi-1, but not NESH/Abi-3, is expressed. The expression of NESH/Abi-3 caused degradation of endogenous Abi-1, which led to the formation of a NESH/Abi-3-based WAVE2 complex
GO:0035591 signaling adaptor activity	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for signaling adaptor activity. ABI3 functions as an adaptor protein within the WRC, linking upstream signals to actin cytoskeleton regulation. It contains an SH3 domain and proline-rich regions typical of adaptor proteins; ABI3 is an adaptor whose C-terminal SH3 domain seems to interact with PAK (PMID:11956071), and it also associates with IRSp53/BAIAP2 (PMID:18480067, domain mapping unspecified in cached title-only record). Reason: ABI3 is a well-characterized adaptor protein. Its SH3 domain mediates protein-protein interactions and it serves as a bridge within the WRC to couple signaling to actin regulation. This accurately captures the molecular function of ABI3. Supporting Evidence: PMID:11956071 The SH3 domain of NESH seems to interact with p21-activated kinase (PAK), which is involved in regulation of cell motility
GO:0098858 actin-based cell projection	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for actin-based cell projection localization. ABI3 localizes to actin-based structures as a WRC component. Experimental evidence shows it at lamellipodia and potentially invadopodia (PMID:26428302). Reason: Consistent with ABI3 function as a WRC component that regulates actin-based protrusions. Well-supported by the IDA evidence for lamellipodium localization and the broader role in actin-based structures.
GO:0030334 regulation of cell migration	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation from Amniota ABI3 clade node PTN000825627 for sign-neutral regulation of cell migration through WRC-dependent actin dynamics. Reason: Core conserved role of ABI3 in modulating WRC-dependent cell migration, and sign-neutral GO:0030334 is as precise as warranted rather than refining to GO:0030336 (negative regulation of cell migration): all directional motility-suppression evidence (reduced motility in NESH transfectants in PMID:11956071 and reduced WAVE2 plasma membrane translocation upon exogenous NESH/Abi-3 expression in PMID:26428302) comes exclusively from ectopic/forced overexpression—the same gain-of-function perturbation type marked MARK_AS_OVER_ANNOTATED on GO:0002357 (PMID:21223585) and ABI1 GO:0008285—whereas no endogenous loss-of-function cell-migration directionality data are cited and endogenous microglial ABI3 migration consequences remain an open question (suggested_questions / suggested_experiments). Supporting Evidence: PMID:11956071 every clone of NESH transfectants caused a marked reduction in motility, although the clones exhibited no significant differences in intrinsic cell growth compared with the control cells in vitro PMID:26428302 When these cells were plated on fibronectin-coated dishes, the translocation of WAVE2 to the plasma membrane was significantly reduced and the formation of peripheral lamellipodial structures was disturbed
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation from UniProt subcellular location mapping. Cytoplasmic localization is supported by IDA evidence (GO_REF:0000054) and NAS from PMID:11956071. UniProt states ABI3 localizes to the cytoplasm and colocalizes with PAK2 at the leading edge of cells. Reason: Consistent with experimental evidence for cytoplasmic localization. Broad IEA mapping is acceptable given strong experimental support.
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	REMOVE	Summary: Protein binding annotation from high-throughput interactome study. Reason: Bare GO:0005515 (protein binding) is uninformative per the protein-binding policy; removal reflects lack of functional specificity rather than falsity of physical interaction, while ABI3's molecular role is captured by GO:0035591 (signaling adaptor activity).
GO:0005515 protein binding	IPI PMID:17101133 NESH (Abi-3) is present in the Abi/WAVE complex but does not...	MODIFY	Summary: Protein binding from PMID:17101133 demonstrating that ABI3/NESH incorporates into the Abi/WAVE complex. Reason: Bare GO:0005515 is uninformative per the protein-binding policy; PMID:17101133 establishes ABI3/NESH as a component of the Abi/WAVE complex, warranting refinement to GO:0035591 (signaling adaptor activity). Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:17101133 Immunoprecipitation revealed that NESH (Abi-3) is present in the Abi/WAVE complex
GO:0005515 protein binding	IPI PMID:19060904 An empirical framework for binary interactome mapping.	REMOVE	Summary: Protein binding from high-throughput binary interactome mapping study. Reason: Bare GO:0005515 (protein binding) is uninformative per the protein-binding policy; removal reflects lack of functional specificity rather than falsity of physical interaction.
GO:0005515 protein binding	IPI PMID:21516116 Next-generation sequencing to generate interactome datasets.	REMOVE	Summary: Protein binding from next-generation sequencing interactome dataset. Reason: Bare GO:0005515 (protein binding) is uninformative per the protein-binding policy; removal reflects lack of functional specificity rather than falsity of physical interaction.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	REMOVE	Summary: Protein binding from proteome-scale interactome mapping. Reason: Bare GO:0005515 (protein binding) is uninformative per the protein-binding policy; removal reflects lack of functional specificity rather than falsity of physical interaction.
GO:0005515 protein binding	IPI PMID:27107014 An inter-species protein-protein interaction network across ...	REMOVE	Summary: Protein binding from inter-species protein-protein interaction network study. Reason: Bare GO:0005515 (protein binding) is uninformative per the protein-binding policy; removal reflects lack of functional specificity rather than falsity of physical interaction.
GO:0005515 protein binding	IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m...	REMOVE	Summary: Protein binding from interactome perturbation framework study. Reason: Bare GO:0005515 (protein binding) is uninformative per the protein-binding policy; removal reflects lack of functional specificity rather than falsity of physical interaction.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Protein binding from reference binary protein interactome map. Reason: Bare GO:0005515 (protein binding) is uninformative per the protein-binding policy; removal reflects lack of functional specificity rather than falsity of physical interaction.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	REMOVE	Summary: Protein binding from multimodal cell maps study. Reason: Bare GO:0005515 (protein binding) is uninformative per the protein-binding policy; removal reflects lack of functional specificity rather than falsity of physical interaction.
GO:0042802 identical protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	KEEP AS NON CORE	Summary: Self-interaction of ABI3 detected in the HI-II-14 binary yeast two-hybrid human interactome screen (PMID:25416956). Reason: ABI3 homodimerization is reproducibly detected across two independent binary yeast two-hybrid interactome screens (HI-II-14 in PMID:25416956 and HuRI in PMID:32296183), but self-association is non-core relative to heteropentameric WAVE regulatory complex assembly (harmonized with mouse Abi3).
GO:0042802 identical protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	KEEP AS NON CORE	Summary: Additional binary yeast two-hybrid evidence for ABI3 self-interaction from the HuRI reference interactome map (PMID:32296183). Reason: Independent binary Y2H confirmation of ABI3 self-interaction across HuRI (PMID:32296183) and HI-II-14 (PMID:25416956); retained as non-core relative to heteropentameric WAVE regulatory complex assembly (harmonized with mouse Abi3).
GO:0002357 defense response to tumor cell	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Automated IEA annotation derived from ectopic ABI3 re-expression suppressing carcinoma xenograft growth (PMID:21223585). Reason: ARBA:ARBA00089051\|UniProtKB:Q8BYZ1 on human ABI3 and ARBA:ARBA00089051\|UniProtKB:Q9P2A4 on mouse Abi3 circularly cite each other back to PMID:21223585; GO:0002357 denotes host/immune defense against a tumor cell, whereas PMID:21223585 demonstrates cell-autonomous suppression of anchorage-independent growth and motility with increased cellular senescence upon ectopic ABI3 re-expression in carcinoma cell lines, so this row is harmonized as MARK_AS_OVER_ANNOTATED with the IMP row. Supporting Evidence: PMID:21223585 Ectopic expression of ABI3 was sufficient to lead to a lower transforming activity, reduced tumor in vitro growth properties, suppressed in vitro anchorage-independent growth and in vivo tumor formation while, cellular senescence increased
GO:0010593 negative regulation of lamellipodium assembly	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation transferred from mouse ortholog. Supported by experimental evidence in PMID:26428302 showing that ABI3/NESH expression in NIH3T3 cells reduced WAVE2 translocation to the plasma membrane and disturbed lamellipodial formation. Reason: This is a well-supported function of ABI3. The ABI3-based WAVE2 complex is functionally distinct and impairs lamellipodial protrusion formation compared to ABI1-based complexes. Supporting Evidence: PMID:26428302 the translocation of WAVE2 to the plasma membrane was significantly reduced and the formation of peripheral lamellipodial structures was disturbed
GO:0030027 lamellipodium	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for lamellipodium localization. Consistent with IDA evidence from PMID:17101133 and IBA annotation. Reason: Redundant with IBA and IDA annotations but not incorrect. Lamellipodium localization is well established for ABI3.
GO:0031209 SCAR complex	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for SCAR complex membership. Consistent with IDA annotations from PMID:17101133 and PMID:26428302. Reason: Core function. Redundant with IDA annotations but acceptable.
GO:0098794 postsynapse	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: IEA annotation transferred from rat ortholog via Ensembl Compara. ISS annotations from ARUK-UCL also support postsynaptic localization (dendritic spine, postsynaptic density). The WRC functions in dendritic spine morphogenesis, supporting synaptic localization. However, ABI3 is primarily enriched in microglia rather than neurons. Reason: While WRC-mediated actin regulation at the postsynapse is conserved for ABI family members, ABI3 is primarily expressed in microglia in the brain, not neurons. The synaptic annotations may be more relevant to ABI1/ABI2 and transferred to ABI3 by orthology. Keep as non-core pending direct evidence in neurons.
GO:0098885 modification of postsynaptic actin cytoskeleton	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: IEA annotation from rat ortholog. WRC-dependent actin modification at postsynapses is a known function of ABI family members. However, ABI3 is primarily microglial rather than neuronal in the brain. Reason: Plausible by orthology and WRC function but ABI3 is not the primary ABI family member in neurons. This function may be more attributable to ABI1/ABI2.
GO:0098978 glutamatergic synapse	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: IEA annotation transferred from rat ortholog. Glutamatergic synapse localization may be more relevant to ABI1/ABI2 given ABI3 enrichment in microglia. Reason: Transferred from rat ortholog. ABI3 is microglia-enriched in brain tissue and not primarily neuronal. This annotation may reflect function of other ABI paralogs rather than ABI3 specifically.
GO:1903077 negative regulation of protein localization to plasma membrane	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation from mouse ortholog. Supported by experimental evidence showing that ABI3 expression reduces WAVE2 translocation to the plasma membrane (PMID:26428302). Reason: Well-supported by experimental data. ABI3-containing WAVE2 complexes show reduced translocation to the plasma membrane compared to ABI1-containing complexes, consistent with this annotation. Supporting Evidence: PMID:26428302 the translocation of WAVE2 to the plasma membrane was significantly reduced
GO:0030036 actin cytoskeleton organization	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation transferred by curator judgment. ABI3 participates in actin cytoskeleton organization as a WRC component. The WRC activates Arp2/3-mediated actin nucleation and polymerization. Reason: Core function of ABI3. As a WRC subunit, ABI3 directly participates in actin cytoskeleton organization, represented in core_functions[0] alongside the more specific negative-regulation and migration terms (GO:0010593 and GO:0030334) in core_functions[1-2] (which sit on distinct GO branches rather than as is_a/part_of descendants of GO:0030036).
GO:0002357 defense response to tumor cell	IMP PMID:21223585 ABI3 ectopic expression reduces in vitro and in vivo cell gr...	MARK AS OVER ANNOTATED	Summary: IMP annotation from PMID:21223585 showing that ABI3 ectopic expression reduces tumor growth in vitro and in vivo in thyroid and colon carcinoma cell lines. ABI3 expression is frequently lost in carcinomas, and re-expression reduces transforming activity, anchorage-independent growth, and in vivo tumor formation. Reason: PMID:21223585 demonstrates cell-autonomous suppression of anchorage-independent growth, motility, and xenograft tumor formation alongside increased cellular senescence upon ectopic ABI3 re-expression in carcinoma cell lines where ABI3 was silenced. Because GO:0002357 denotes host/immune defense against a tumor cell rather than cell-autonomous motility/senescence modulation upon ectopic overexpression, this term represents an over-annotation (harmonized with mouse Abi3). Supporting Evidence: PMID:21223585 Ectopic expression of ABI3 was sufficient to lead to a lower transforming activity, reduced tumor in vitro growth properties, suppressed in vitro anchorage-independent growth and in vivo tumor formation while, cellular senescence increased
GO:2000774 positive regulation of cellular senescence	IMP PMID:21223585 ABI3 ectopic expression reduces in vitro and in vivo cell gr...	KEEP AS NON CORE	Summary: IMP annotation from PMID:21223585. ABI3 ectopic expression induced senescence in thyroid and colon carcinoma cells, accompanied by p21WAF1 upregulation and reduced ERK phosphorylation. Reason: The experimental evidence for senescence induction is clear from PMID:21223585. However, this is likely a secondary consequence of ABI3 re-expression in cancer cells rather than a core evolved function. This effect is observed in the context of ectopic expression in cells where ABI3 was silenced, and the senescence phenotype may reflect disruption of oncogenic signaling rather than a primary ABI3 function. Supporting Evidence: PMID:21223585 cellular senescence increased. These responses were accompanied by the up-regulation of the cell cycle inhibitor p21 WAF1 and reduced ERK phosphorylation and E2F1 expression
GO:0031209 SCAR complex	IDA PMID:17101133 NESH (Abi-3) is present in the Abi/WAVE complex but does not...	ACCEPT	Summary: IDA annotation from PMID:17101133 demonstrating ABI3 is present in the Abi/WAVE complex by immunoprecipitation. This is a key finding establishing ABI3 as a bona fide WRC component. Reason: Core function. Direct experimental evidence from immunoprecipitation showing ABI3 is a component of the WAVE complex. Supporting Evidence: PMID:17101133 Immunoprecipitation revealed that NESH (Abi-3) is present in the Abi/WAVE complex. Our results suggest that NESH (Abi-3), like Abi-1 and Abi-2, is a component of the Abi/WAVE complex
GO:0043197 dendritic spine	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS annotation transferred from a rat ortholog (F1M0R2) by ARUK-UCL curators. WRC components are known to localize to dendritic spines where they regulate spine morphogenesis. However, ABI3 is primarily microglial in the brain. Reason: While WRC function at dendritic spines is conserved for ABI family members, ABI3 is microglia-enriched in the brain. This annotation may primarily reflect the function of ABI1/ABI2 in neurons, transferred by sequence similarity.
GO:0043198 dendritic shaft	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS annotation transferred from rat ortholog. Similar considerations as for dendritic spine localization. Reason: ABI3 is microglia-enriched rather than neuronal. This annotation may reflect function of other ABI paralogs. Keeping as non-core.
GO:0014069 postsynaptic density	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS annotation transferred from rat ortholog. Postsynaptic density localization is well-established for WRC components, but ABI3 is primarily microglial. Reason: Same reasoning as for dendritic spine. WRC function at the PSD is conserved for ABI family but ABI3 enrichment in microglia suggests this is not its primary localization context.
GO:0051015 actin filament binding	ISS GO_REF:0000024	UNDECIDED	Summary: ISS annotation transferred from rat ortholog. ABI3 contains domains that could mediate interactions with actin-based structures, but direct actin filament binding by ABI3 itself has not been demonstrated. ABI3 functions as an adaptor within the WRC rather than directly binding actin filaments. Reason: There is no direct evidence for ABI3 binding actin filaments. ABI3 interacts with actin-regulatory complexes (WRC) but its function is as an adaptor, not an actin-binding protein per se. The ISS transfer may be from a different ABI paralog with distinct biochemical properties. More evidence needed to confirm direct actin filament binding by ABI3.
GO:0061001 regulation of dendritic spine morphogenesis	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS annotation from rat ortholog. WRC regulates dendritic spine morphogenesis but ABI3 is microglia-enriched, not primarily neuronal. Reason: WRC function in spine morphogenesis is well-established but likely mediated by ABI1/ABI2 in neurons. ABI3 is primarily expressed in microglia.
GO:0099151 regulation of postsynaptic density assembly	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS annotation from rat ortholog. Similar considerations as other synaptic annotations. Reason: ABI3 is microglia-enriched and not the primary ABI paralog at neuronal synapses. Keep as non-core.
GO:1900028 negative regulation of ruffle assembly	NAS PMID:18480067 Insulin receptor substrate protein 53 (IRSp53) as a binding ...	ACCEPT	Summary: NAS annotation from PMID:18480067 (title-only Ann Oncol letter in local cache) for negative regulation of ruffle assembly, corroborated by ABI3-WAVE2 complex functional assays in PMID:26428302. Reason: PMID:18480067 is cached locally as title-only (full_text_available: false, full_text_unavailable: true), identifying IRSp53 as a binding partner of NESH/ABI3 without inspectable body text; ACCEPT defers to the curator's NAS reading of PMID:18480067, corroborated by full-text evidence in PMID:26428302 showing that ABI3-containing WAVE2 complexes reduce WAVE2 plasma-membrane translocation and disturb peripheral lamellipodial protrusion assembly. Supporting Evidence: PMID:26428302 the translocation of WAVE2 to the plasma membrane was significantly reduced and the formation of peripheral lamellipodial structures was disturbed
GO:0010593 negative regulation of lamellipodium assembly	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation from mouse ortholog. Strongly supported by experimental evidence in PMID:26428302 showing ABI3-containing WAVE2 complexes impair lamellipodium formation. Reason: This is a core function distinguishing ABI3 from ABI1/ABI2. ABI3-based WAVE2 complexes are functionally distinct and impair lamellipodial protrusions. Supporting Evidence: PMID:26428302 the NESH/Abi-3-based WAVE2 complex was unable to help produce lamellipodial protrusions
GO:0031209 SCAR complex	IDA PMID:26428302 The NESH/Abi-3-based WAVE2 complex is functionally distinct ...	ACCEPT	Summary: IDA annotation from PMID:26428302 providing detailed characterization of the ABI3-based WAVE2 complex. Demonstrated that ABI3 expression leads to degradation of endogenous ABI1 and formation of an ABI3-based WAVE2 complex. Reason: Core function. Independent confirmation of SCAR/WAVE complex membership with detailed functional characterization of the distinct ABI3-containing complex. Supporting Evidence: PMID:26428302 The expression of NESH/Abi-3 caused degradation of endogenous Abi-1, which led to the formation of a NESH/Abi-3-based WAVE2 complex
GO:1903077 negative regulation of protein localization to plasma membrane	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation from mouse ortholog. ABI3 expression reduces WAVE2 translocation to the plasma membrane, as shown in PMID:26428302. Reason: Well-supported by experimental data. ABI3-containing WAVE2 complexes show reduced membrane translocation compared to ABI1-containing complexes. Supporting Evidence: PMID:26428302 the translocation of WAVE2 to the plasma membrane was significantly reduced
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	KEEP AS NON CORE	Summary: Membrane association is documented for this protein, so the generic membrane term is true, but it is not the protein's core location. Reason: UniProt: cytoplasm, colocalizing with PAK2 at the leading edge (ECO:0000269); ABI3 is a WAVE regulatory complex subunit recruited to the leading-edge membrane. Plausible peripheral association, not a core location. (Manual re-review for OMICS_EVIDENCE, 2026-10-10; previous action: ACCEPT.)
GO:0005737 cytoplasm	IDA GO_REF:0000054	ACCEPT	Summary: IDA annotation from LIFEdb based on intracellular localization of expressed fusion proteins in living cells. Consistent with UniProt subcellular location annotation. Reason: Cytoplasmic localization is well-established for ABI3. Supported by multiple independent evidence sources.
GO:0018108 peptidyl-tyrosine phosphorylation	IDA NOT PMID:17101133 NESH (Abi-3) is present in the Abi/WAVE complex but does not...	ACCEPT	Summary: CORRECT negative annotation. PMID:17101133 explicitly tested and showed that "NESH (Abi-3) had no such effect" on promoting c-Abl-mediated phosphorylation, unlike Abi-1 and Abi-2 which do promote this activity. This negative annotation correctly captures that ABI3/NESH does NOT participate in peptidyl-tyrosine phosphorylation processes. Reason: Important negative annotation that distinguishes ABI3 from its paralogs ABI1 and ABI2. PMID:17101133 directly tested and demonstrated this difference. Supporting Evidence: PMID:17101133 Although Abi-2, like Abi-1, promoted the c-Abl-mediated phosphorylation of Mena and WAVE2, NESH (Abi-3) had no such effect. This difference was likely due to their binding abilities as to c-Abl
GO:0030027 lamellipodium	IDA PMID:17101133 NESH (Abi-3) is present in the Abi/WAVE complex but does not...	ACCEPT	Summary: IDA annotation from PMID:17101133 (abstract-only in local cache) for ABI3 localization at lamellipodia, consistent with its WAVE complex incorporation. Reason: PMID:17101133 is abstract-only (full_text_available: false) in the local publication cache and its abstract summarizes NESH (Abi-3) co-immunoprecipitation in the Abi/WAVE complex and lack of c-Abl phosphorylation rather than fluorescence microscopy or subcellular localization; ACCEPT therefore defers to the curator's full-text IDA evaluation of PMID:17101133, consistent with ABI3's established subunit role in the WAVE regulatory complex (PMID:17101133). Supporting Evidence: PMID:17101133 Immunoprecipitation revealed that NESH (Abi-3) is present in the Abi/WAVE complex
GO:0030334 regulation of cell migration	IDA PMID:11956071 Forced expression of NESH suppresses motility and metastatic...	ACCEPT	Summary: IDA annotation from PMID:11956071 (abstract-only in local cache) for sign-neutral regulation of cell migration based on reduced cell motility upon forced NESH/ABI3 expression. Reason: Core conserved role of ABI3 in modulating WRC-dependent cell migration (reported directly in the abstract of PMID:11956071, full_text_available: false, and deferred to the curator's full-text IDA evaluation), and sign-neutral GO:0030334 is as precise as warranted rather than refining to GO:0030336 (negative regulation of cell migration): all directional motility-suppression evidence (reduced motility in NESH transfectants in PMID:11956071 and reduced WAVE2 membrane translocation upon exogenous NESH/Abi-3 expression in PMID:26428302) comes exclusively from ectopic/forced overexpression—the same gain-of-function perturbation type marked MARK_AS_OVER_ANNOTATED on GO:0002357 (PMID:21223585) and ABI1 GO:0008285—whereas no endogenous loss-of-function cell-migration directionality data are cited and endogenous microglial ABI3 migration consequences remain an open question (suggested_questions / suggested_experiments). Supporting Evidence: PMID:11956071 every clone of NESH transfectants caused a marked reduction in motility, although the clones exhibited no significant differences in intrinsic cell growth compared with the control cells in vitro. The NESH transfectants also exhibited significant reduction in tumor metastatic potential in vivo PMID:26428302 When these cells were plated on fibronectin-coated dishes, the translocation of WAVE2 to the plasma membrane was significantly reduced and the formation of peripheral lamellipodial structures was disturbed
GO:0005737 cytoplasm	NAS PMID:11956071 Forced expression of NESH suppresses motility and metastatic...	ACCEPT	Summary: NAS annotation from PMID:11956071 (abstract-only in local cache) for cytoplasmic localization of the intracellular SH3 adaptor NESH/ABI3. Reason: PMID:11956071 is abstract-only (full_text_available: false) in the local cache, where its abstract describes NESH inhibiting cell migration through interaction with intracellular molecules such as PAK rather than reporting a direct subcellular localization quotation; ACCEPT defers to the curator's full-text NAS reading of PMID:11956071, reinforced by the companion LIFEdb live-cell GFP-fusion IDA annotation on GO:0005737 (GO_REF:0000054) and ABI3's incorporation into the cytoplasmic WAVE2 regulatory complex.

Gene Description

Existing Annotations Review

Core Functions

Component of the WAVE regulatory complex (WRC/SCAR complex), occupying the Abi subunit position. ABI3 forms a heteropentameric complex with WAVE2, CYFIP1, NAP1, and BRK1 that couples upstream signals (Rac, Arf GTPases) to Arp2/3-mediated actin nucleation and polymerization.

Negative regulation of lamellipodium assembly and membrane ruffling. ABI3-based WAVE2 complexes specifically impair the formation of peripheral lamellipodial structures, distinguishing ABI3 from ABI1 and ABI2 in terms of protrusion type regulation.

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