id: Q9NYB9
gene_symbol: ABI2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  ABI2 (Abl interactor 2) is a non-enzymatic adaptor/scaffold protein of the ABI family that functions
  as a core subunit of the WAVE regulatory complex (WRC). The WRC is a heteropentameric complex
  composed of WAVE/SCAR, CYFIP/SRA1, NCKAP1/NAP1, ABI (ABI1/ABI2/ABI3), and BRK1/HSPC300 that
  controls Arp2/3-mediated branched actin nucleation at the plasma membrane leading edge. Within
  the WRC, ABI2 forms a helical bundle trimer with WAVE and BRK1 that contacts the SRA1:NAP1
  dimer platform (PMID:21107423). ABI2 contains an N-terminal HHR (Hox homology region) involved
  in WRC assembly and a C-terminal SH3 domain that mediates binding to Abl/Arg family tyrosine
  kinases (PMID:7590236, PMID:8649853). ABI2 acts as both a regulator and substrate of ABL1 and
  ABL2 kinases, and promotes ABL1-mediated phosphorylation of targets such as ENAH and WAVE2
  (PMID:17101133). ABI2 localizes to the tips of lamellipodia and filopodia where it regulates
  actin polymerization dynamics underlying cell motility and adhesion (PMID:11516653). ABI2 is
  also regulated by TRIM32-mediated ubiquitin-dependent degradation (PMID:18632609) and PIM1
  phosphorylation at Ser183 which stabilizes ABI2 and promotes tumor invasion (Jensen et al. 2023,
  J Cell Biol). ABI2-deficient mice show defective cell migration, aberrant dendritic spine
  morphogenesis, and learning/memory deficits (PMID:15572692), and loss-of-function variants in
  ABI2 have been linked to autosomal recessive intellectual disability (PMID:28397838). ABI2 shares
  approximately 74% sequence identity with ABI1 and the two can compensate for each other in some
  contexts.
existing_annotations:
  # === IBA annotations (phylogenetic) ===
  - term:
      id: GO:0048858
      label: cell projection morphogenesis
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:21107423
          supporting_text: >-
            The WRC is inactive towards the Arp2/3 complex, but can be stimulated by the Rac
            GTPase, kinases and phosphatidylinositols
        - reference_id: PMID:11516653
          supporting_text: >-
            Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited
            to the tips of lamellipodia and filopodia

  - term:
      id: GO:0001764
      label: neuron migration
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:15572692
          supporting_text: >-
            [UniProt reference] ABI2-deficient mice exhibit defective cell migration, aberrant
            dendritic spine morphogenesis, and deficits in learning and memory

  - term:
      id: GO:0030027
      label: lamellipodium
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:11516653
          supporting_text: >-
            Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited
            to the tips of lamellipodia and filopodia

  - term:
      id: GO:0031209
      label: SCAR complex
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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).
      supported_by:
        - reference_id: PMID:21107423
          supporting_text: >-
            MiniWRC can be delineated into two subcomplexes: an Sra1:Nap1 dimer and a
            WAVE1:Abi2:HSPC300 trimer
        - reference_id: PMID:17101133
          supporting_text: >-
            Abi-2, like Abi-1, promoted the c-Abl-mediated phosphorylation of Mena and WAVE2

  - term:
      id: GO:0035591
      label: signaling adaptor activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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).
      supported_by:
        - reference_id: PMID:8649853
          supporting_text: >-
            ArgBP1 contains a C-terminal SH3 domain, several PEST sequences, a serine rich domain
            and an SH3 binding site
        - reference_id: file:human/ABI2/ABI2-deep-research-falcon.md
          supporting_text: >-
            ABI2 (Abi-2) is a SH3-containing Abl interactor (an adaptor/scaffold rather than
            an enzyme)

  - term:
      id: GO:0098858
      label: actin-based cell projection
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      reason: >-
        Well-supported by direct microscopy evidence showing ABI2 at lamellipodia and filopodia
        tips (PMID:11516653). Consistent with the IBA lamellipodium annotation.
      supported_by:
        - reference_id: PMID:11516653
          supporting_text: >-
            Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited
            to the tips of lamellipodia and filopodia

  # === IEA annotations (electronic) ===
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.

  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      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.
      action: ACCEPT
      reason: >-
        Cytoplasm is a correct and well-supported localization for ABI2. PMID:8649853 directly
        demonstrated cytoplasmic localization by immunostaining.
      supported_by:
        - reference_id: PMID:8649853
          supporting_text: >-
            Immunostaining indicated that the subcellular localization of ArgBP1 is cytoplasmic

  - term:
      id: GO:0005856
      label: cytoskeleton
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      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.
      action: ACCEPT
      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.

  - term:
      id: GO:0005912
      label: adherens junction
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        ABI2 localizes to nascent adherens junctions based on UniProt annotation citing
        PMID:15572692. ABI2-deficient cells show impaired adherens junction assembly.
      action: KEEP_AS_NON_CORE
      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.

  - term:
      id: GO:0007399
      label: nervous system development
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      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).
      action: KEEP_AS_NON_CORE
      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.

  - term:
      id: GO:0017124
      label: SH3 domain binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:8649853
          supporting_text: >-
            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

  - term:
      id: GO:0030027
      label: lamellipodium
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        Duplicate of the IBA lamellipodium annotation. This IEA mapping from UniProt subcellular
        location is consistent with experimental evidence from PMID:11516653.
      action: ACCEPT
      reason: >-
        Lamellipodium localization is well-established for ABI2 (PMID:11516653, PMID:15572692).
        Duplicate with IBA annotation but both are valid.

  - term:
      id: GO:0030175
      label: filopodium
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        ABI2 localizes to filopodia tips as shown by PMID:11516653. UniProt notes filopodium
        localization for isoform 1.
      action: ACCEPT
      reason: >-
        Filopodium localization is directly demonstrated by EYFP-Abi-2b fusion experiments
        (PMID:11516653). The IEA mapping is consistent with experimental evidence.
      supported_by:
        - reference_id: PMID:11516653
          supporting_text: >-
            Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited
            to the tips of lamellipodia and filopodia

  - term:
      id: GO:0031209
      label: SCAR complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        Duplicate of IBA SCAR complex annotation. ABI2 is a structurally confirmed component
        of the WRC/SCAR complex (PMID:21107423).
      action: ACCEPT
      reason: >-
        ARBA prediction is consistent with structural and biochemical evidence. Duplicate
        with IBA annotation but both are valid.

  - term:
      id: GO:0032433
      label: filopodium tip
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ABI2 localizes to filopodium tips as directly demonstrated by EYFP fusion experiments
        (PMID:11516653). The ARBA prediction is consistent with experimental evidence.
      action: ACCEPT
      reason: >-
        Filopodium tip localization is experimentally validated (PMID:11516653).
      supported_by:
        - reference_id: PMID:11516653
          supporting_text: >-
            Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited
            to the tips of lamellipodia and filopodia

  - term:
      id: GO:0035591
      label: signaling adaptor activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        Duplicate of IBA signaling adaptor activity annotation. ABI2 is indeed a signaling
        adaptor protein.
      action: ACCEPT
      reason: >-
        Consistent with IBA annotation and experimental evidence. ABI2 functions as an
        adaptor linking upstream signals to actin nucleation machinery.

  # === IPI protein binding annotations ===
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:12463424
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:12463424
          supporting_text: >-
            the interaction regions have been identified. They are the SH3 binding sites in
            ADAM19-CT and the P4 region in ArgBP1

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16189514
    review:
      summary: >-
        PMID:16189514 is a high-throughput proteome-scale interaction mapping study. Protein
        binding detected in large-scale screens.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic 'protein binding' from a high-throughput interaction study is uninformative
        for ABI2's specific function.

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17101133
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:17101133
          supporting_text: >-
            Abi-2, like Abi-1, promoted the c-Abl-mediated phosphorylation of Mena and WAVE2

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19523119
    review:
      summary: >-
        PMID:19523119 identified ABI2 interaction with CASK-interactive protein1 (CASKIN1).
        High-throughput interaction study context.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic 'protein binding' is uninformative. The specific interaction partner
        context is not captured.

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21516116
    review:
      summary: >-
        PMID:21516116 is a next-generation sequencing based interactome study. High-throughput
        interaction data.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic 'protein binding' from high-throughput interactome study is uninformative.

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25416956
    review:
      summary: >-
        PMID:25416956 is a proteome-scale human interactome mapping study. High-throughput
        interaction data.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic 'protein binding' from high-throughput interactome study is uninformative.

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:29892012
    review:
      summary: >-
        PMID:29892012 is an interactome perturbation framework study. High-throughput
        interaction data.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic 'protein binding' from high-throughput interactome study is uninformative.

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:31515488
    review:
      summary: >-
        PMID:31515488 characterizes disruption of protein interactions by genetic variants.
        High-throughput interaction data.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic 'protein binding' from high-throughput study is uninformative.

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:33961781
    review:
      summary: >-
        PMID:33961781 describes dual proteome-scale interactome networks. High-throughput
        interaction data.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic 'protein binding' from high-throughput interactome study is uninformative.

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:40205054
    review:
      summary: >-
        PMID:40205054 describes multimodal cell maps. High-throughput interaction data.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        Generic 'protein binding' from high-throughput study is uninformative.

  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: IPI
    original_reference_id: PMID:25416956
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.

  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: IPI
    original_reference_id: PMID:29892012
    review:
      summary: >-
        Duplicate identical protein binding annotation from another high-throughput study.
      action: KEEP_AS_NON_CORE
      reason: >-
        Same as above - ABI2 self-interaction from high-throughput data. Not well-characterized
        as a core function.

  # === IDA/experimental annotations ===
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: >-
        Nucleoplasm localization from immunofluorescence data curation (HPA). ABI2 may
        have some nuclear presence though its primary functional location is the cell cortex.
      action: KEEP_AS_NON_CORE
      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.

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: >-
        Cytosol localization from immunofluorescence data curation (HPA). Consistent with
        ABI2 being a cytoplasmic protein that is recruited to membrane/cortex upon WRC
        activation.
      action: ACCEPT
      reason: >-
        Cytosol is the expected resting localization for ABI2 prior to membrane recruitment
        via WRC activation by Rac1. Consistent with multiple experimental observations.

  - term:
      id: GO:0000423
      label: mitophagy
    evidence_type: IDA
    original_reference_id: PMID:38081847
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:38081847
          supporting_text: >-
            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

  - term:
      id: GO:0035591
      label: signaling adaptor activity
    evidence_type: IDA
    original_reference_id: PMID:17101133
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:17101133
          supporting_text: >-
            Abi-2, like Abi-1, promoted the c-Abl-mediated phosphorylation of Mena and WAVE2

  - term:
      id: GO:0010592
      label: positive regulation of lamellipodium assembly
    evidence_type: IDA
    original_reference_id: PMID:21107423
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:21107423
          supporting_text: >-
            WAVE regulates lamellipodia formation within a 400-kilodalton, hetero-pentameric
            WAVE regulatory complex (WRC)

  - term:
      id: GO:0035591
      label: signaling adaptor activity
    evidence_type: IDA
    original_reference_id: PMID:21107423
    review:
      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.
      action: ACCEPT
      reason: >-
        Structural evidence from the WRC crystal structure directly supports ABI2 as a
        signaling adaptor that bridges upstream signals to Arp2/3 activation.
      supported_by:
        - reference_id: PMID:21107423
          supporting_text: >-
            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

  # === ISS annotations ===
  - term:
      id: GO:0043197
      label: dendritic spine
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      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).
      action: KEEP_AS_NON_CORE
      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.

  - term:
      id: GO:0061001
      label: regulation of dendritic spine morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      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).
      action: KEEP_AS_NON_CORE
      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.

  - term:
      id: GO:0070309
      label: lens fiber cell morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      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).
      action: KEEP_AS_NON_CORE
      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.

  # === More IDA/experimental annotations ===
  - term:
      id: GO:0016601
      label: Rac protein signal transduction
    evidence_type: IDA
    original_reference_id: PMID:21107423
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:21107423
          supporting_text: >-
            Rac plays an important role in controlling actin polymerization and lamellipodia
            formation through activation of the WRC in vivo

  - term:
      id: GO:0031267
      label: small GTPase binding
    evidence_type: IDA
    original_reference_id: PMID:21107423
    review:
      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.
      action: MODIFY
      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_replacement_terms:
        - id: GO:0035591
          label: signaling adaptor activity
      supported_by:
        - reference_id: PMID:21107423
          supporting_text: >-
            Sra1 mutations C179R, R190D, M632D and E434K/F626A, severely impaired binding
            of ΔWRC to Rac1

  - term:
      id: GO:0032433
      label: filopodium tip
    evidence_type: IDA
    original_reference_id: PMID:11516653
    review:
      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.
      action: ACCEPT
      reason: >-
        Direct experimental evidence from EYFP-Abi-2b localization in living cells
        (PMID:11516653). This is a well-validated localization.
      supported_by:
        - reference_id: PMID:11516653
          supporting_text: >-
            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

  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24439377
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.

  - term:
      id: GO:0031209
      label: SCAR complex
    evidence_type: IDA
    original_reference_id: PMID:21107423
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:21107423
          supporting_text: >-
            MiniWRC can be delineated into two subcomplexes: an Sra1:Nap1 dimer and a
            WAVE1:Abi2:HSPC300 trimer

  - term:
      id: GO:2000601
      label: positive regulation of Arp2/3 complex-mediated actin nucleation
    evidence_type: IDA
    original_reference_id: PMID:21107423
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:21107423
          supporting_text: >-
            The WRC is inactive towards the Arp2/3 complex, but can be stimulated by the Rac
            GTPase, kinases and phosphatidylinositols

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IDA
    original_reference_id: PMID:18632609
    review:
      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.
      action: ACCEPT
      reason: >-
        Cytosol localization is well-established for ABI2 and is consistent with its role
        as a cytoplasmic adaptor protein.
      supported_by:
        - reference_id: PMID:18632609
          supporting_text: >-
            TRIM32 binds to Abl-interactor 2 (Abi2)...and we showed that TRIM32 mediates
            the ubiquitination of Abi2

  - term:
      id: GO:0031625
      label: ubiquitin protein ligase binding
    evidence_type: IPI
    original_reference_id: PMID:18632609
    review:
      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.
      action: ACCEPT
      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'.
      supported_by:
        - reference_id: PMID:18632609
          supporting_text: >-
            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

  - term:
      id: GO:0030027
      label: lamellipodium
    evidence_type: IDA
    original_reference_id: PMID:11516653
    review:
      summary: >-
        PMID:11516653 directly demonstrated that EYFP-Abi-2b localizes to lamellipodia
        in living, motile cells.
      action: ACCEPT
      reason: >-
        Direct experimental evidence from EYFP-Abi-2b localization in living cells
        (PMID:11516653). This is a core localization for ABI2.
      supported_by:
        - reference_id: PMID:11516653
          supporting_text: >-
            Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited
            to the tips of lamellipodia and filopodia

  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IDA
    original_reference_id: PMID:17101133
    review:
      summary: >-
        PMID:17101133 studied ABI2 in the context of the Abi/WAVE complex. Cytosol localization
        is implied by the biochemical fractionation and immunoprecipitation experiments.
      action: ACCEPT
      reason: >-
        Cytosol localization is consistent with ABI2 as a cytoplasmic adaptor protein.

  - term:
      id: GO:0018108
      label: peptidyl-tyrosine phosphorylation
    evidence_type: IDA
    original_reference_id: PMID:17101133
    review:
      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.
      action: MODIFY
      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_replacement_terms:
        - id: GO:0045862
          label: positive regulation of proteolysis
        - id: GO:0045860
          label: positive regulation of protein kinase activity
      supported_by:
        - reference_id: PMID:17101133
          supporting_text: >-
            Abi-2, like Abi-1, promoted the c-Abl-mediated phosphorylation of Mena and WAVE2

  # === TAS/NAS annotations ===
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: TAS
    original_reference_id: PMID:8649853
    review:
      summary: >-
        PMID:8649853 demonstrated cytoplasmic localization of ABI2 (ArgBP1) by immunostaining
        in the original identification paper.
      action: ACCEPT
      reason: >-
        Direct experimental evidence from immunostaining (PMID:8649853). Cytoplasm is a
        well-established localization for ABI2.
      supported_by:
        - reference_id: PMID:8649853
          supporting_text: >-
            Immunostaining indicated that the subcellular localization of ArgBP1 is cytoplasmic

  - term:
      id: GO:0017124
      label: SH3 domain binding
    evidence_type: TAS
    original_reference_id: PMID:8649853
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:8649853
          supporting_text: >-
            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

  - term:
      id: GO:0007010
      label: cytoskeleton organization
    evidence_type: TAS
    original_reference_id: PMID:12011975
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:12011975
          supporting_text: >-
            Some of the members of this family are involved in cytoskeletal reorganization
            that plays important roles in membrane-ruffling, lamellipodia formation and
            cell migration

  - term:
      id: GO:0008093
      label: cytoskeletal anchor activity
    evidence_type: TAS
    original_reference_id: PMID:12011975
    review:
      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.
      action: MODIFY
      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_replacement_terms:
        - id: GO:0035591
          label: signaling adaptor activity

  - term:
      id: GO:0008154
      label: actin polymerization or depolymerization
    evidence_type: NAS
    original_reference_id: PMID:11516653
    review:
      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.
      action: MODIFY
      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_replacement_terms:
        - id: GO:0030832
          label: regulation of actin filament length

  - term:
      id: GO:0016477
      label: cell migration
    evidence_type: TAS
    original_reference_id: PMID:12011975
    review:
      summary: >-
        PMID:12011975 reviews ABI family involvement in cell migration. ABI2-deficient mice
        show defective cell migration (PMID:15572692).
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:12011975
          supporting_text: >-
            Some of the members of this family are involved in cytoskeletal reorganization
            that plays important roles in membrane-ruffling, lamellipodia formation and
            cell migration

  - term:
      id: GO:0019900
      label: kinase binding
    evidence_type: NAS
    original_reference_id: PMID:8649853
    review:
      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).
      action: ACCEPT
      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).
      supported_by:
        - reference_id: PMID:8649853
          supporting_text: >-
            ArgBP1 is likely to be a regulator and/or effector of Arg function

references:
  - id: GO_REF:0000024
    title: Manual transfer of experimentally-verified manual GO annotation data
      to orthologs by curator judgment of sequence similarity
    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:0000117
    title: Electronic Gene Ontology annotations created by ARBA machine learning
      models
    findings: []
  - id: PMID:7590236
    title: Abi-2, a novel SH3-containing protein interacts with the c-Abl tyrosine
      kinase and modulates c-Abl transforming activity.
    findings:
      - statement: >-
          ABI2 was originally identified as an SH3-containing protein that interacts with
          c-Abl and modulates its transforming activity. ABI2 is phosphorylated by ABL1
          and its SH3 domain mediates binding to Abl kinases.
  - id: PMID:8649853
    title: Identification of ArgBP1, an Arg protein tyrosine kinase binding protein
      that is the human homologue of a CNS-specific Xenopus gene.
    findings:
      - statement: >-
          ABI2 (ArgBP1) was identified as an Arg kinase binding protein containing SH3
          domain, PEST sequences, and proline-rich region. The SH3 domain binds Arg
          C-terminal SH3-binding site, and N-terminal proline-rich sequence binds Arg SH3
          domain. Cytoplasmic localization was demonstrated by immunostaining.
  - id: PMID:11516653
    title: The Abl interactor proteins localize to sites of actin polymerization
      at the tips of lamellipodia and filopodia.
    findings:
      - statement: >-
          EYFP-Abi-2b was shown to localize to the tips of lamellipodia and filopodia in
          living, motile cells. The targeting domain was identified as the homologous N
          terminus.
  - id: PMID:12011975
    title: In search of a function for the E3B1/Abi2/Argbp1/NESH family (Review).
    findings:
      - statement: >-
          Review describing ABI family members as adaptor proteins involved in cytoskeletal
          reorganization, membrane ruffling, lamellipodia formation, and cell migration.
  - id: PMID:12463424
    title: Screen and identification of proteins interacting with ADAM19 cytoplasmic
      tail.
    findings:
      - statement: >-
          ABI2 (ArgBP1) identified as ADAM19 cytoplasmic tail interacting protein by yeast
          two-hybrid. Interaction mapped to SH3 binding sites in ADAM19-CT and P4 region
          in ABI2.
  - id: PMID:15572692
    title: ABI2-deficient mice exhibit defective cell migration, aberrant dendritic
      spine morphogenesis, and deficits in learning and memory.
    findings:
      - statement: >-
          ABI2 knockout mice show defective cell migration, aberrant dendritic spine
          morphogenesis, and impaired learning and memory. ABI2 localizes to lamellipodia
          and nascent adherens junctions. Required for adherens junction assembly.
  - id: PMID:16189514
    title: Towards a proteome-scale map of the human protein-protein interaction
      network.
    findings: []
  - id: PMID:17101133
    title: NESH (Abi-3) is present in the Abi/WAVE complex but does not promote
      c-Abl-mediated phosphorylation.
    findings:
      - statement: >-
          ABI2, like ABI1, promotes c-Abl-mediated phosphorylation of Mena and WAVE2.
          ABI2 is present in the Abi/WAVE complex. In contrast, ABI3 (NESH) does not
          promote c-Abl-mediated phosphorylation due to reduced c-Abl binding.
  - id: PMID:18632609
    title: Tripartite motif protein 32 facilitates cell growth and migration via
      degradation of Abl-interactor 2.
    findings:
      - statement: >-
          TRIM32 directly binds ABI2 and mediates its ubiquitination and proteasomal
          degradation. TRIM32 overexpression promotes ABI2 degradation, enhancing cell
          growth, transformation, and motility.
  - id: PMID:19523119
    title: High levels of structural disorder in scaffold proteins as exemplified
      by a novel neuronal protein, CASK-interactive protein1.
    findings: []
  - id: PMID:21107423
    title: Structure and control of the actin regulatory WAVE complex.
    findings:
      - statement: >-
          2.3 angstrom crystal structure of the WRC reveals ABI2 as part of the
          WAVE1:ABI2:HSPC300 trimer that contacts the SRA1:NAP1 dimer platform. The
          WAVE VCA is sequestered by SRA1 and the meander region. Rac1 binds to SRA1
          to activate the complex. This defines the structural basis for WRC regulation
          of Arp2/3-mediated actin nucleation.
  - id: PMID:21516116
    title: Next-generation sequencing to generate interactome datasets.
    findings: []
  - id: PMID:24439377
    title: Local F-actin network links synapse formation and axon branching.
    findings: []
  - id: PMID:25416956
    title: A proteome-scale map of the human interactome network.
    findings: []
  - id: PMID:28397838
    title: Mapping autosomal recessive intellectual disability - combined microarray
      and exome sequencing identifies 26 novel candidate genes in 192 consanguineous
      families.
    findings:
      - statement: >-
          Loss-of-function variant in ABI2 identified in consanguineous family with
          autosomal recessive intellectual disability.
  - id: PMID:29892012
    title: An interactome perturbation framework prioritizes damaging missense
      mutations for developmental disorders.
    findings: []
  - id: PMID:31515488
    title: Extensive disruption of protein interactions by genetic variants across
      the allele frequency spectrum in human populations.
    findings: []
  - id: PMID:33961781
    title: Dual proteome-scale networks reveal cell-specific remodeling of the
      human interactome.
    findings: []
  - id: PMID:38081847
    title: GRAF1 integrates PINK1-Parkin signaling and actin dynamics to mediate
      cardiac mitochondrial homeostasis.
    findings:
      - statement: >-
          ABI2 was identified as a GRAF1-interacting protein enriched in phosphorylated
          GRAF1 immunoprecipitates. GRAF1 depletion reduced ABI2:WAVE2 complex formation
          and recruitment of WAVE2 complex (WAVE2, ABI2, CYFIP1) to damaged mitochondria.
          ABI2 recruits WAVE2 to promote Arp2/3-dependent branched actin remodeling
          necessary for mitochondrial clearance.
  - id: PMID:40205054
    title: Multimodal cell maps as a foundation for structural and functional
      genomics.
    findings: []
  - id: file:human/ABI2/ABI2-deep-research-falcon.md
    title: ABI2 deep research report (Falcon)
    findings:
      - statement: >-
          Comprehensive review of ABI2 function including PIM1 phosphorylation at Ser183
          stabilizing ABI2, promoting WRC function and tumor invasion. ABI2 shares 74%
          identity with ABI1.

core_functions:
  - description: >-
      ABI2 functions as a signaling adaptor protein within the WAVE regulatory complex (WRC),
      coupling upstream Rac1 GTPase signaling to Arp2/3-mediated branched actin nucleation
      at the leading edge of migrating cells. ABI2 forms a helical bundle trimer with WAVE
      and BRK1/HSPC300, serving as a structural bridge within the pentameric WRC. Through
      this role, ABI2 promotes lamellipodia formation, cell migration, and cytoskeletal
      reorganization.
    molecular_function:
      id: GO:0035591
      label: signaling adaptor activity
    directly_involved_in:
      - id: GO:0010592
        label: positive regulation of lamellipodium assembly
      - id: GO:2000601
        label: positive regulation of Arp2/3 complex-mediated actin nucleation
      - id: GO:0016601
        label: Rac protein signal transduction
      - id: GO:0016477
        label: cell migration
      - id: GO:0007010
        label: cytoskeleton organization
    locations:
      - id: GO:0030027
        label: lamellipodium
      - id: GO:0032433
        label: filopodium tip
      - id: GO:0005829
        label: cytosol
    in_complex:
      id: GO:0031209
      label: SCAR complex

  - description: >-
      ABI2 interacts with Abl/Arg family non-receptor tyrosine kinases via its SH3 domain
      and proline-rich regions, acting as both a regulator and substrate of ABL1 and ABL2.
      ABI2 promotes c-Abl-mediated phosphorylation of downstream targets including ENAH/Mena
      and WAVE2, coupling kinase signaling to actin polymerization.
    molecular_function:
      id: GO:0019900
      label: kinase binding
    directly_involved_in:
      - id: GO:0045860
        label: positive regulation of protein kinase activity
    locations:
      - id: GO:0005829
        label: cytosol