ABI2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0048858 cell projection morphogenesis	IBA GO_REF:0000033	ACCEPT	Summary: ABI2 is a core component of the WAVE regulatory complex that drives lamellipodia and filopodia formation through Arp2/3-mediated actin nucleation (PMID:21107423). ABI2-deficient mice show defective cell migration and aberrant dendritic spine morphogenesis (PMID:15572692). Cell projection morphogenesis is a well-supported biological process for ABI2 via its role in the WRC. Reason: ABI2 directly regulates actin dynamics underlying cell projections as part of the WRC. ABI2-knockout mouse data from PMID:15572692 shows dendritic spine morphogenesis defects and the protein localizes to lamellipodia and filopodia tips (PMID:11516653). This IBA annotation is phylogenetically sound and experimentally validated. Supporting Evidence: PMID:21107423 The WRC is inactive towards the Arp2/3 complex, but can be stimulated by the Rac GTPase, kinases and phosphatidylinositols PMID:11516653 Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited to the tips of lamellipodia and filopodia
GO:0001764 neuron migration	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: ABI2-deficient mice exhibit defective cell migration (PMID:15572692), and ABI2 functions within the WRC which controls actin-dependent motility. Neuron migration is supported by ABI2 knockout mouse phenotypes showing deficits in learning and memory and dendritic spine abnormalities. Reason: While ABI2 clearly contributes to cell migration generally via its role in the WRC, neuron migration is a more specialized process. The IBA annotation is reasonable given neuronal phenotypes in ABI2-KO mice, but this represents a tissue-specific downstream consequence rather than a core function of the protein. Supporting Evidence: PMID:15572692 [UniProt reference] ABI2-deficient mice exhibit defective cell migration, aberrant dendritic spine morphogenesis, and deficits in learning and memory
GO:0030027 lamellipodium	IBA GO_REF:0000033	ACCEPT	Summary: ABI2 localizes to lamellipodia as shown by fluorescent protein fusion experiments (PMID:11516653) and is a component of the WRC that drives lamellipodia formation (PMID:21107423). This is a core localization for ABI2. Reason: Lamellipodium localization is well-established experimentally. PMID:11516653 directly demonstrated EYFP-Abi-2b recruitment to lamellipodia tips, and the WRC crystal structure (PMID:21107423) confirms ABI2 as a structural component of the WRC that promotes lamellipodia formation. Supporting Evidence: PMID:11516653 Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited to the tips of lamellipodia and filopodia
GO:0031209 SCAR complex	IBA GO_REF:0000033	ACCEPT	Summary: ABI2 is a bona fide subunit of the WAVE/SCAR regulatory complex (WRC). The 2.3 angstrom crystal structure of the WRC (PMID:21107423) directly shows ABI2 as part of the WAVE1:ABI2:HSPC300 trimer subcomplex that contacts the SRA1:NAP1 dimer. Reason: This is a core annotation. ABI2 membership in the SCAR/WAVE complex is demonstrated structurally at atomic resolution (PMID:21107423) and confirmed by multiple biochemical studies (PMID:17101133). Supporting Evidence: PMID:21107423 MiniWRC can be delineated into two subcomplexes: an Sra1:Nap1 dimer and a WAVE1:Abi2:HSPC300 trimer PMID:17101133 Abi-2, like Abi-1, promoted the c-Abl-mediated phosphorylation of Mena and WAVE2
GO:0035591 signaling adaptor activity	IBA GO_REF:0000033	ACCEPT	Summary: ABI2 is a prototypical adaptor protein with no catalytic activity. It functions as a scaffold within the WRC, linking upstream signals (Rac1, kinases) to downstream Arp2/3 activation. Its SH3 domain mediates interactions with Abl/Arg kinases, and it serves as a bridge between signaling inputs and actin nucleation machinery. Reason: Signaling adaptor activity accurately captures ABI2's molecular function. It has HHR and SH3 domains for protein-protein interactions, no enzymatic activity, and functions by coupling upstream signals to the WRC and Arp2/3 complex (PMID:21107423, PMID:8649853). Supporting Evidence: PMID:8649853 ArgBP1 contains a C-terminal SH3 domain, several PEST sequences, a serine rich domain and an SH3 binding site file:human/ABI2/ABI2-deep-research-falcon.md ABI2 (Abi-2) is a SH3-containing Abl interactor (an adaptor/scaffold rather than an enzyme)
GO:0098858 actin-based cell projection	IBA GO_REF:0000033	ACCEPT	Summary: ABI2 localizes to actin-based cell projections including lamellipodia and filopodia (PMID:11516653). This is a broader CC term encompassing the more specific lamellipodium and filopodium localizations. Reason: Well-supported by direct microscopy evidence showing ABI2 at lamellipodia and filopodia tips (PMID:11516653). Consistent with the IBA lamellipodium annotation. Supporting Evidence: PMID:11516653 Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited to the tips of lamellipodia and filopodia
GO:0005634 nucleus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Nuclear localization of ABI2 is supported by UniProt annotation based on the original characterization by PMID:7590236 which showed some nuclear localization. HPA data (GO_REF:0000052) also supports nucleoplasm localization. Reason: While ABI2 may be found in the nucleus, its primary functional localization is at the cell cortex/lamellipodia as part of the WRC. Nuclear localization is likely secondary. The IEA mapping from UniProt subcellular location is acceptable but non-core.
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: ABI2 is a cytoplasmic protein as shown by immunostaining in PMID:8649853. The cytoplasmic localization is well-established and consistent with its role in the WRC at the cell cortex. Reason: Cytoplasm is a correct and well-supported localization for ABI2. PMID:8649853 directly demonstrated cytoplasmic localization by immunostaining. Supporting Evidence: PMID:8649853 Immunostaining indicated that the subcellular localization of ArgBP1 is cytoplasmic
GO:0005856 cytoskeleton	IEA GO_REF:0000044	ACCEPT	Summary: ABI2 associates with cytoskeletal structures through its role in the WRC and localization to actin-rich structures. UniProt notes cytoskeletal localization for isoform 1 based on PMID:15572692. Reason: ABI2 functions at sites of actin polymerization and associates with the actin cytoskeleton via the WRC. This is a broad but accurate CC annotation consistent with UniProt data.
GO:0005912 adherens junction	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: ABI2 localizes to nascent adherens junctions based on UniProt annotation citing PMID:15572692. ABI2-deficient cells show impaired adherens junction assembly. Reason: Adherens junction localization is supported by PMID:15572692 but represents a secondary localization site compared to lamellipodia/filopodia. It reflects ABI2's role in actin-dependent cell-cell adhesion rather than its primary function.
GO:0007399 nervous system development	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: ABI2 has roles in nervous system development as shown by ABI2-KO mouse phenotypes including dendritic spine morphogenesis defects and learning/memory deficits (PMID:15572692). Loss-of-function variants are linked to intellectual disability (PMID:28397838). Reason: While ABI2 contributes to nervous system development, this is a broad pleiotropic consequence of its core function in actin regulation via the WRC, not a dedicated neurodevelopmental function. The IEA mapping from UniProt keywords is reasonable but non-core.
GO:0017124 SH3 domain binding	IEA GO_REF:0000117	ACCEPT	Summary: ABI2 contains a C-terminal SH3 domain and binds SH3 domains of Abl/Arg kinases. PMID:8649853 demonstrated that the ABI2 proline-rich sequence binds to the Arg SH3 domain, and ABI2's own SH3 domain binds to Arg C-terminal SH3-binding site. Reason: SH3 domain binding is a well-characterized molecular function of ABI2, established in the original identification papers (PMID:7590236, PMID:8649853). The ARBA prediction is consistent with experimental data. Supporting Evidence: PMID:8649853 the ArgBP1 SH3 domain binds to a C-terminal Arg SH3-binding site, and that an N-terminal ArgBP1 proline-rich sequence binds to the Arg SH3 domain
GO:0030027 lamellipodium	IEA GO_REF:0000044	ACCEPT	Summary: Duplicate of the IBA lamellipodium annotation. This IEA mapping from UniProt subcellular location is consistent with experimental evidence from PMID:11516653. Reason: Lamellipodium localization is well-established for ABI2 (PMID:11516653, PMID:15572692). Duplicate with IBA annotation but both are valid.
GO:0030175 filopodium	IEA GO_REF:0000044	ACCEPT	Summary: ABI2 localizes to filopodia tips as shown by PMID:11516653. UniProt notes filopodium localization for isoform 1. Reason: Filopodium localization is directly demonstrated by EYFP-Abi-2b fusion experiments (PMID:11516653). The IEA mapping is consistent with experimental evidence. Supporting Evidence: PMID:11516653 Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited to the tips of lamellipodia and filopodia
GO:0031209 SCAR complex	IEA GO_REF:0000117	ACCEPT	Summary: Duplicate of IBA SCAR complex annotation. ABI2 is a structurally confirmed component of the WRC/SCAR complex (PMID:21107423). Reason: ARBA prediction is consistent with structural and biochemical evidence. Duplicate with IBA annotation but both are valid.
GO:0032433 filopodium tip	IEA GO_REF:0000117	ACCEPT	Summary: ABI2 localizes to filopodium tips as directly demonstrated by EYFP fusion experiments (PMID:11516653). The ARBA prediction is consistent with experimental evidence. Reason: Filopodium tip localization is experimentally validated (PMID:11516653). Supporting Evidence: PMID:11516653 Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited to the tips of lamellipodia and filopodia
GO:0035591 signaling adaptor activity	IEA GO_REF:0000117	ACCEPT	Summary: Duplicate of IBA signaling adaptor activity annotation. ABI2 is indeed a signaling adaptor protein. Reason: Consistent with IBA annotation and experimental evidence. ABI2 functions as an adaptor linking upstream signals to actin nucleation machinery.
GO:0005515 protein binding	IPI PMID:12463424 Screen and identification of proteins interacting with ADAM1...	MARK AS OVER ANNOTATED	Summary: PMID:12463424 identified ABI2 (as ArgBP1) as a binding partner of the ADAM19 cytoplasmic tail by yeast two-hybrid screening and GST-pulldown. The interaction was mapped to the SH3 binding sites in ADAM19-CT and the P4 region in ABI2. Reason: The generic 'protein binding' term is uninformative. The actual function is SH3 domain-mediated protein-protein interaction. However, the ADAM19 interaction may not represent a core function of ABI2. Supporting Evidence: PMID:12463424 the interaction regions have been identified. They are the SH3 binding sites in ADAM19-CT and the P4 region in ArgBP1
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	MARK AS OVER ANNOTATED	Summary: PMID:16189514 is a high-throughput proteome-scale interaction mapping study. Protein binding detected in large-scale screens. Reason: Generic 'protein binding' from a high-throughput interaction study is uninformative for ABI2's specific function.
GO:0005515 protein binding	IPI PMID:17101133 NESH (Abi-3) is present in the Abi/WAVE complex but does not...	MARK AS OVER ANNOTATED	Summary: PMID:17101133 compared ABI family members and showed ABI2 is present in the Abi/WAVE complex and promotes c-Abl-mediated phosphorylation of Mena and WAVE2. The interaction with the WAVE complex and c-Abl is well-characterized. Reason: The 'protein binding' term fails to capture the specific functional interactions (WAVE complex subunit, Abl kinase binding) that are the informative aspects of this study. Supporting Evidence: PMID:17101133 Abi-2, like Abi-1, promoted the c-Abl-mediated phosphorylation of Mena and WAVE2
GO:0005515 protein binding	IPI PMID:19523119 High levels of structural disorder in scaffold proteins as e...	MARK AS OVER ANNOTATED	Summary: PMID:19523119 identified ABI2 interaction with CASK-interactive protein1 (CASKIN1). High-throughput interaction study context. Reason: Generic 'protein binding' is uninformative. The specific interaction partner context is not captured.
GO:0005515 protein binding	IPI PMID:21516116 Next-generation sequencing to generate interactome datasets.	MARK AS OVER ANNOTATED	Summary: PMID:21516116 is a next-generation sequencing based interactome study. High-throughput interaction data. Reason: Generic 'protein binding' from high-throughput interactome study is uninformative.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: PMID:25416956 is a proteome-scale human interactome mapping study. High-throughput interaction data. Reason: Generic 'protein binding' from high-throughput interactome study is uninformative.
GO:0005515 protein binding	IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m...	MARK AS OVER ANNOTATED	Summary: PMID:29892012 is an interactome perturbation framework study. High-throughput interaction data. Reason: Generic 'protein binding' from high-throughput interactome study is uninformative.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: PMID:31515488 characterizes disruption of protein interactions by genetic variants. High-throughput interaction data. Reason: Generic 'protein binding' from high-throughput study is uninformative.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: PMID:33961781 describes dual proteome-scale interactome networks. High-throughput interaction data. Reason: Generic 'protein binding' from high-throughput interactome study is uninformative.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: PMID:40205054 describes multimodal cell maps. High-throughput interaction data. Reason: Generic 'protein binding' from high-throughput study is uninformative.
GO:0042802 identical protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	KEEP AS NON CORE	Summary: ABI2 self-interaction (homodimerization) is supported by IntAct data showing ABI2:ABI2 interactions with 3 independent experiments (UniProt CC INTERACTION section). This is consistent with ABI family members forming dimers. Reason: ABI2 self-interaction is documented in IntAct but is from high-throughput data. While ABI family oligomerization is plausible, this is not well-characterized as a core function.
GO:0042802 identical protein binding	IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m...	KEEP AS NON CORE	Summary: Duplicate identical protein binding annotation from another high-throughput study. Reason: Same as above - ABI2 self-interaction from high-throughput data. Not well-characterized as a core function.
GO:0005654 nucleoplasm	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: Nucleoplasm localization from immunofluorescence data curation (HPA). ABI2 may have some nuclear presence though its primary functional location is the cell cortex. Reason: While HPA immunofluorescence data may show some nucleoplasm signal, ABI2's primary functional localization is at the cell cortex/lamellipodia as part of the WRC. Nuclear localization is secondary and its functional relevance is unclear.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: Cytosol localization from immunofluorescence data curation (HPA). Consistent with ABI2 being a cytoplasmic protein that is recruited to membrane/cortex upon WRC activation. Reason: Cytosol is the expected resting localization for ABI2 prior to membrane recruitment via WRC activation by Rac1. Consistent with multiple experimental observations.
GO:0000423 mitophagy	IDA PMID:38081847 GRAF1 integrates PINK1-Parkin signaling and actin dynamics t...	MARK AS OVER ANNOTATED	Summary: PMID:38081847 identifies ABI2 as recruited to damaged mitochondria via interaction with phosphorylated GRAF1, where it facilitates WAVE2 complex formation and Arp2/3- dependent branched actin remodeling necessary for mitochondrial clearance. GRAF1 depletion reduced ABI2:WAVE2 complex formation and OA-dependent recruitment of the WAVE2 complex (WAVE2, ABI2, CYFIP1) to mitochondria. However, ABI2 itself was not directly knocked down or shown to be required for mitophagy; rather, it was shown to be recruited as part of the WRC downstream of GRAF1. Reason: While PMID:38081847 provides compelling evidence that ABI2 is recruited to damaged mitochondria as part of the WAVE2 complex through GRAF1 interaction, the study focused on GRAF1 as the mitophagy regulator. ABI2 was identified as a GRAF1-interacting protein and shown to be recruited to mitochondria, but direct evidence for ABI2 being required for mitophagy (e.g., ABI2 knockdown/knockout mitophagy assays) was not presented. ABI2's involvement appears to be through its general role in actin remodeling via WRC rather than a specific mitophagy function. Supporting Evidence: PMID:38081847 GRAF1 phosphorylation is induced in a PINK1-Parkin dependent fashion on damaged mitochondria which leads to ABI2 recruitment, WAVE2 complex formation and Arp2/3-dependent branched actin formation that is necessary for mitochondrial clearance
GO:0035591 signaling adaptor activity	IDA PMID:17101133 NESH (Abi-3) is present in the Abi/WAVE complex but does not...	ACCEPT	Summary: PMID:17101133 showed that ABI2, like ABI1, is a component of the Abi/WAVE complex and promotes c-Abl-mediated phosphorylation of Mena and WAVE2. This is consistent with adaptor function linking Abl kinases to downstream targets. Reason: ABI2 acts as an adaptor bridging c-Abl kinase activity to downstream substrates Mena and WAVE2. This is a core molecular function consistent with its domain architecture (SH3 and HHR domains) and lack of catalytic activity. Supporting Evidence: PMID:17101133 Abi-2, like Abi-1, promoted the c-Abl-mediated phosphorylation of Mena and WAVE2
GO:0010592 positive regulation of lamellipodium assembly	IDA PMID:21107423 Structure and control of the actin regulatory WAVE complex.	ACCEPT	Summary: PMID:21107423 resolved the crystal structure of the WRC at 2.3 angstroms and demonstrated that the WRC (containing ABI2) activates Arp2/3 complex upon Rac1 stimulation, driving lamellipodium assembly. Constitutively activating mutations in WRC components caused redistribution of actin to the cell periphery and loss of stress fibers, consistent with lamellipodium assembly. Reason: This is a core function of ABI2 as a WRC component. The WRC directly controls lamellipodia formation through Arp2/3 activation, and ABI2 is an essential subunit. Supporting Evidence: PMID:21107423 WAVE regulates lamellipodia formation within a 400-kilodalton, hetero-pentameric WAVE regulatory complex (WRC)
GO:0035591 signaling adaptor activity	IDA PMID:21107423 Structure and control of the actin regulatory WAVE complex.	ACCEPT	Summary: PMID:21107423 provides structural evidence for ABI2 as an adaptor within the WRC. ABI2 forms a four-helix bundle with WAVE1 and HSPC300 that connects to the SRA1:NAP1 dimer, serving as a structural bridge for signal transduction. Reason: Structural evidence from the WRC crystal structure directly supports ABI2 as a signaling adaptor that bridges upstream signals to Arp2/3 activation. Supporting Evidence: PMID:21107423 A long four-helix bundle created by a helix from HSPC300 (residues 14-68), two helices from Abi2 (residues 1-39 and 43-112) and a helix from WAVE1 (residues 26-81) contacts Sra1 extensively
GO:0043197 dendritic spine	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ABI2 localization to dendritic spines is supported by mouse ortholog data. ABI2-deficient mice show aberrant dendritic spine morphogenesis (PMID:15572692), and ABI2 may promote mushroom-type spine specification (UniProt, by similarity). Reason: Dendritic spine localization is plausible based on mouse model data but represents a neuron-specific localization that is a consequence of ABI2's general actin regulatory function rather than a core localization.
GO:0061001 regulation of dendritic spine morphogenesis	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ABI2-deficient mice show aberrant dendritic spine morphogenesis (PMID:15572692). ABI2 may promote mushroom-type spine specification via its role in actin regulation (UniProt, by similarity). Reason: Regulation of dendritic spine morphogenesis is a neuron-specific downstream consequence of ABI2's core role in actin regulation via the WRC. The ISS transfer from mouse ortholog data is reasonable but represents a non-core function.
GO:0070309 lens fiber cell morphogenesis	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ABI2 participates in ocular lens morphogenesis by regulating lamellipodia-driven adherens junction formation at the epithelial cell-secondary lens fiber interface (UniProt, by similarity from mouse ortholog data). Reason: Lens fiber cell morphogenesis is a tissue-specific downstream consequence of ABI2's actin regulatory function. This is a specialized developmental role transferred by sequence similarity and represents a non-core function.
GO:0016601 Rac protein signal transduction	IDA PMID:21107423 Structure and control of the actin regulatory WAVE complex.	ACCEPT	Summary: PMID:21107423 demonstrated that the WRC (containing ABI2) is activated by Rac1-GTP, which binds to SRA1 and destabilizes VCA sequestration, leading to Arp2/3 activation. ABI2 is part of the complex that transduces Rac signaling. Reason: The WRC is a major effector of Rac1 signaling, and ABI2 is a core component. Rac1 binding to SRA1 within the WRC triggers conformational changes that release the WAVE VCA motif and activate Arp2/3. This is a core function of ABI2 as a WRC subunit. Supporting Evidence: PMID:21107423 Rac plays an important role in controlling actin polymerization and lamellipodia formation through activation of the WRC in vivo
GO:0031267 small GTPase binding	IDA PMID:21107423 Structure and control of the actin regulatory WAVE complex.	MODIFY	Summary: PMID:21107423 characterized Rac1 binding to the WRC. However, Rac1 binds to SRA1 within the complex, not directly to ABI2. The annotation of small GTPase binding to ABI2 is misleading as it is the WRC complex, specifically SRA1, that binds Rac1. Reason: The small GTPase binding annotation is problematic because Rac1 binds to SRA1/CYFIP1, not directly to ABI2. ABI2 is part of the complex that is activated by Rac1 but does not itself bind the GTPase. This annotation should be replaced with a more accurate term reflecting ABI2's role in the complex. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:21107423 Sra1 mutations C179R, R190D, M632D and E434K/F626A, severely impaired binding of ΔWRC to Rac1
GO:0032433 filopodium tip	IDA PMID:11516653 The Abl interactor proteins localize to sites of actin polym...	ACCEPT	Summary: PMID:11516653 directly demonstrated that EYFP-Abi-2b localizes to filopodium tips in living, motile cells. The N-terminal domain was identified as the targeting domain. Reason: Direct experimental evidence from EYFP-Abi-2b localization in living cells (PMID:11516653). This is a well-validated localization. Supporting Evidence: PMID:11516653 Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited to the tips of lamellipodia and filopodia. We identify the targeting domain as the homologous N terminus of these two proteins
GO:0005515 protein binding	IPI PMID:24439377 Local F-actin network links synapse formation and axon branc...	MARK AS OVER ANNOTATED	Summary: PMID:24439377 showed that the WRC (including ABI2) is recruited to synaptic sites through interaction with synaptic cell adhesion molecule SYG-1 via a WIRS motif. This is a C. elegans study using the WRC. Reason: Generic 'protein binding' is uninformative. The study demonstrates WRC recruitment to synaptic sites via specific receptor-complex interactions, but the annotation does not capture this specificity.
GO:0031209 SCAR complex	IDA PMID:21107423 Structure and control of the actin regulatory WAVE complex.	ACCEPT	Summary: PMID:21107423 resolved the crystal structure of the WRC at 2.3 angstroms, directly showing ABI2 as part of the WAVE1:ABI2:HSPC300 trimer within the pentameric WRC. This is the definitive structural evidence for ABI2 membership in the SCAR/WAVE complex. Reason: Atomic-resolution structural evidence from X-ray crystallography (PMID:21107423) directly confirms ABI2 as a SCAR/WAVE complex component. This is a core annotation. Supporting Evidence: PMID:21107423 MiniWRC can be delineated into two subcomplexes: an Sra1:Nap1 dimer and a WAVE1:Abi2:HSPC300 trimer
GO:2000601 positive regulation of Arp2/3 complex-mediated actin nucleation	IDA PMID:21107423 Structure and control of the actin regulatory WAVE complex.	ACCEPT	Summary: PMID:21107423 demonstrated that the WRC (containing ABI2) activates the Arp2/3 complex upon Rac1 stimulation. Constitutively activating mutations released the WAVE VCA motif and stimulated Arp2/3-mediated actin nucleation. This is the core mechanistic function of the WRC. Reason: Positive regulation of Arp2/3 complex-mediated actin nucleation is the central mechanistic output of the WRC, and ABI2 is a required structural component. This is a core annotation. Supporting Evidence: PMID:21107423 The WRC is inactive towards the Arp2/3 complex, but can be stimulated by the Rac GTPase, kinases and phosphatidylinositols
GO:0005829 cytosol	IDA PMID:18632609 Tripartite motif protein 32 facilitates cell growth and migr...	ACCEPT	Summary: PMID:18632609 studied TRIM32-mediated ubiquitination and degradation of ABI2. The study showed ABI2 in the cytosol where it is targeted for degradation by TRIM32. Reason: Cytosol localization is well-established for ABI2 and is consistent with its role as a cytoplasmic adaptor protein. Supporting Evidence: PMID:18632609 TRIM32 binds to Abl-interactor 2 (Abi2)...and we showed that TRIM32 mediates the ubiquitination of Abi2
GO:0031625 ubiquitin protein ligase binding	IPI PMID:18632609 Tripartite motif protein 32 facilitates cell growth and migr...	ACCEPT	Summary: PMID:18632609 demonstrated direct binding of ABI2 to TRIM32 E3 ubiquitin ligase by yeast two-hybrid screening, and showed TRIM32 mediates ABI2 ubiquitination and degradation. This is a functionally validated protein-protein interaction. Reason: Ubiquitin protein ligase binding is well-supported by direct binding evidence (PMID:18632609). ABI2 is a substrate of TRIM32, and this interaction regulates ABI2 protein levels. More informative than generic 'protein binding'. Supporting Evidence: PMID:18632609 we found by using yeast two-hybrid screening that TRIM32 binds to Abl-interactor 2 (Abi2)...and we showed that TRIM32 mediates the ubiquitination of Abi2
GO:0030027 lamellipodium	IDA PMID:11516653 The Abl interactor proteins localize to sites of actin polym...	ACCEPT	Summary: PMID:11516653 directly demonstrated that EYFP-Abi-2b localizes to lamellipodia in living, motile cells. Reason: Direct experimental evidence from EYFP-Abi-2b localization in living cells (PMID:11516653). This is a core localization for ABI2. Supporting Evidence: PMID:11516653 Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited to the tips of lamellipodia and filopodia
GO:0005829 cytosol	IDA PMID:17101133 NESH (Abi-3) is present in the Abi/WAVE complex but does not...	ACCEPT	Summary: PMID:17101133 studied ABI2 in the context of the Abi/WAVE complex. Cytosol localization is implied by the biochemical fractionation and immunoprecipitation experiments. Reason: Cytosol localization is consistent with ABI2 as a cytoplasmic adaptor protein.
GO:0018108 peptidyl-tyrosine phosphorylation	IDA PMID:17101133 NESH (Abi-3) is present in the Abi/WAVE complex but does not...	MODIFY	Summary: OVER-ANNOTATION: ABI2 is an Abl interactor protein that REGULATES c-Abl kinase-mediated phosphorylation but does not perform phosphorylation itself. PMID:17101133 states "Abi-2, like Abi-1, promoted the c-Abl-mediated phosphorylation of Mena and WAVE2" - c-Abl is the kinase, ABI2 is the regulator. UniProt describes ABI2 as "Acts as a regulator and substrate of nonreceptor tyrosine kinases ABL1 and ABL2". ABI2 has no kinase activity - it is an adapter/scaffold protein component of the WAVE complex. Reason: ABI2 does not perform phosphorylation. It promotes c-Abl-mediated phosphorylation of downstream targets like Mena and WAVE2, acting as a positive regulator of ABL1 kinase activity. The correct annotation should reflect this regulatory role. A more appropriate term would be positive regulation of non-membrane spanning protein tyrosine kinase activity, or more generally regulation of protein kinase activity. Proposed replacements: positive regulation of proteolysis positive regulation of protein kinase activity Supporting Evidence: PMID:17101133 Abi-2, like Abi-1, promoted the c-Abl-mediated phosphorylation of Mena and WAVE2
GO:0005737 cytoplasm	TAS PMID:8649853 Identification of ArgBP1, an Arg protein tyrosine kinase bin...	ACCEPT	Summary: PMID:8649853 demonstrated cytoplasmic localization of ABI2 (ArgBP1) by immunostaining in the original identification paper. Reason: Direct experimental evidence from immunostaining (PMID:8649853). Cytoplasm is a well-established localization for ABI2. Supporting Evidence: PMID:8649853 Immunostaining indicated that the subcellular localization of ArgBP1 is cytoplasmic
GO:0017124 SH3 domain binding	TAS PMID:8649853 Identification of ArgBP1, an Arg protein tyrosine kinase bin...	ACCEPT	Summary: PMID:8649853 showed that ABI2 (ArgBP1) binds to the SH3 domain of Arg kinase via its proline-rich region, and ABI2's own SH3 domain binds to Arg C-terminal SH3-binding site. The association involves two pairs of SH3 domain/proline-rich motif interactions. Reason: SH3 domain binding is a core molecular function of ABI2, established in the original identification paper with detailed domain mapping (PMID:8649853). This represents the basis for ABI2's interactions with Abl/Arg kinases. Supporting Evidence: PMID:8649853 the ArgBP1 SH3 domain binds to a C-terminal Arg SH3-binding site, and that an N-terminal ArgBP1 proline-rich sequence binds to the Arg SH3 domain
GO:0007010 cytoskeleton organization	TAS PMID:12011975 In search of a function for the E3B1/Abi2/Argbp1/NESH family...	ACCEPT	Summary: PMID:12011975 is a review of the E3B1/Abi2/Argbp1/NESH family describing their involvement in cytoskeletal reorganization including membrane ruffling, lamellipodia formation, and cell migration. Reason: Cytoskeleton organization is a core biological process for ABI2, consistent with its role in the WRC and actin dynamics regulation. Well-supported by both review literature and primary experimental evidence. Supporting Evidence: PMID:12011975 Some of the members of this family are involved in cytoskeletal reorganization that plays important roles in membrane-ruffling, lamellipodia formation and cell migration
GO:0008093 cytoskeletal anchor activity	TAS PMID:12011975 In search of a function for the E3B1/Abi2/Argbp1/NESH family...	MODIFY	Summary: PMID:12011975 is a review that discusses ABI family proteins as adaptor proteins involved in cytoskeletal organization. The term 'cytoskeletal anchor activity' implies that ABI2 anchors proteins to the cytoskeleton. Reason: ABI2 does not function primarily as a cytoskeletal anchor. It is an adaptor/scaffold in the WRC that regulates actin nucleation. The more appropriate molecular function is signaling adaptor activity, which is already annotated. The 'cytoskeletal anchor activity' term misrepresents ABI2's actual role. Proposed replacements: signaling adaptor activity
GO:0008154 actin polymerization or depolymerization	NAS PMID:11516653 The Abl interactor proteins localize to sites of actin polym...	MODIFY	Summary: PMID:11516653 showed that ABI proteins localize to sites of actin polymerization, suggesting involvement in actin dynamics. ABI2 does not directly polymerize actin but regulates it through the WRC and Arp2/3 complex. Reason: ABI2 does not directly catalyze actin polymerization or depolymerization. It regulates these processes through the WRC. A more appropriate term would be positive regulation of Arp2/3 complex-mediated actin nucleation (already annotated) or regulation of actin polymerization or depolymerization. Proposed replacements: regulation of actin filament length
GO:0016477 cell migration	TAS PMID:12011975 In search of a function for the E3B1/Abi2/Argbp1/NESH family...	ACCEPT	Summary: PMID:12011975 reviews ABI family involvement in cell migration. ABI2-deficient mice show defective cell migration (PMID:15572692). Reason: Cell migration is a well-supported biological process for ABI2, directly demonstrated by ABI2-KO mouse phenotypes (PMID:15572692) and consistent with its role in lamellipodia formation via the WRC. Supporting Evidence: PMID:12011975 Some of the members of this family are involved in cytoskeletal reorganization that plays important roles in membrane-ruffling, lamellipodia formation and cell migration
GO:0019900 kinase binding	NAS PMID:8649853 Identification of ArgBP1, an Arg protein tyrosine kinase bin...	ACCEPT	Summary: PMID:8649853 identified ABI2 (ArgBP1) as an Arg protein tyrosine kinase binding protein using yeast two-hybrid, confirmed by co-immunoprecipitation. ABI2 also binds ABL1 via its SH3 domain (PMID:7590236). Reason: Kinase binding is a core molecular function of ABI2. It was originally identified as a binding partner of Abl/Arg kinases (PMID:7590236, PMID:8649853), and this interaction is central to its function. ABI2 also binds PIM1 kinase (Jensen et al. 2023, J Cell Biol). Supporting Evidence: PMID:8649853 ArgBP1 is likely to be a regulator and/or effector of Arg function

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

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