Affinage

ABI2

Abl interactor 2 · UniProt Q9NYB9

Length
513 aa
Mass
55.7 kDa
Annotated
2026-06-09
32 papers in source corpus 12 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ABI2 (Abl-interactor 2) is an SH3/proline-rich adaptor protein that couples c-Abl tyrosine kinase signaling to actin cytoskeletal remodeling, originally defined by its specific binding to the SH3 domain and C-terminus of c-Abl through its proline-rich sequences, where it also serves as a c-Abl phosphorylation substrate (PMID:7590236). ABI2 functions as a core component of the WAVE regulatory complex (WRC), and its proper function drives WAVE2-dependent actin nucleation and protrusive activity that governs growth-cone behavior and the multipolar-to-bipolar transition during glia-guided radial neuronal migration (PMID:22617848). Genetic loss of Abi2 in mice produces defective cell migration in the lens, neocortex and hippocampus, abnormal dendritic spine morphology, adherens-junction defects accompanied by downregulation of the WAVE nucleation-promoting factor, and severe memory deficits, establishing ABI2 as a critical regulator of cytoskeletal dynamics at adherens junctions and synaptic structures (PMID:15572692). ABI2 also localizes in puncta within neuronal cell bodies, processes, synaptosomes and growth-cone particles, consistent with its role in Abl signaling at developing synapses (PMID:10995551). ABI2 activity is set by phosphorylation: PIM1 phosphorylates ABI2 at Ser183 to stabilize the protein and enhance WRC assembly, increasing motility and invasion (PMID:37042842), while Pak2-mediated phosphorylation of c-Abl disrupts the ABI2 SH3–c-Abl PxxP interaction (PMID:18161990).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1995 High

    Established ABI2's foundational identity as a direct c-Abl-binding adaptor and substrate, defining the SH3–proline-rich interaction module that anchors all later signaling models.

    Evidence Yeast two-hybrid, in vitro and in vivo binding, kinase substrate assay, and functional mutagenesis of Abl SH3-binding sequences

    PMID:7590236

    Open questions at the time
    • Did not define a cellular cytoskeletal output of the interaction
    • Structural basis of dual SH3/C-terminal binding not resolved
  2. 2000 Medium

    Placed ABI2 protein at synapses and growth cones, localizing Abl-pathway adaptor function to specific neuronal compartments in the developing nervous system.

    Evidence Immunofluorescence, synaptosome/growth-cone fractionation and Western blotting of brain lysates

    PMID:10995551

    Open questions at the time
    • Functional consequence of synaptic localization not tested
    • Identity of the developmentally regulated modifying kinase unknown
  3. 2004 High

    Demonstrated through knockout that ABI2 is required in vivo for cell migration, dendritic spine morphology, adherens-junction integrity and memory, linking it mechanistically to WAVE-dependent actin nucleation.

    Evidence Homozygous Abi2 knockout mouse with behavioral assays, RNAi, and adherens-junction immunolocalization showing WAVE downregulation

    PMID:15572692

    Open questions at the time
    • Did not resolve how ABI2 loss reduces WAVE protein levels
    • Cell-type-specific contributions to the memory phenotype not dissected
  4. 2007 High

    Revealed that the ABI2–c-Abl interaction is switchable, showing Pak2 phosphorylation of c-Abl disrupts ABI2 binding while favoring Crk, establishing competitive regulation of c-Abl partner choice.

    Evidence In vitro Pak2 kinase assay on c-Abl fragments with phospho-mimetic mutagenesis and binding/co-IP quantification

    PMID:18161990

    Open questions at the time
    • Cellular contexts where this switch operates not defined
    • Downstream actin consequence of ABI2 displacement not measured
  5. 2012 Medium

    Connected the WAVE2-ABI2 complex to a defined developmental step, showing Abl/Cdk5 phosphorylation of WAVE2 controls growth-cone activity and the multipolar-to-bipolar transition during radial migration.

    Evidence Time-lapse lattice imaging, WAVE2 phospho-site mutagenesis, and in vivo cortical positioning analysis

    PMID:22617848

    Open questions at the time
    • Direct ABI2 phospho-regulation in this step not isolated
    • Single-lab phenotype
  6. 2023 High

    Identified PIM1 phosphorylation of ABI2 at Ser183 as a stabilizing modification that promotes WRC assembly and motility, providing a kinase input that tunes ABI2 abundance and protrusive output.

    Evidence Unbiased PIM1 substrate proteomics, in vitro kinase assay, Ser183 mutagenesis, WRC co-IP, protrusion and in vivo invasion assays with PIM inhibitors

    PMID:37042842

    Open questions at the time
    • Mechanism by which Ser183 phosphorylation stabilizes the protein unknown
    • Relationship to CBLC-mediated degradation not tested
  7. 2016 Low

    Proposed ABI2 in a Nox4-ROS-ABI2-DRF cascade controlling linear actin nucleation, with TIS21/BTG2 reducing ABI2 stability.

    Evidence Cell-based overexpression/knockdown, STED microscopy, ROS measurement and Western blotting

    PMID:27932314

    Open questions at the time
    • No direct biochemical reconstitution of an ABI2-DRF interaction
    • Pathway placement inferred only from expression-level changes
  8. 2022 Low

    Posited that ABI2 normally restrains ABL1 kinase activity and that PRR16/Largen binding relieves this inhibition to promote EMT.

    Evidence Co-IP/binding screen, siRNA silencing, ABL1 Y412 phospho-Western and migration/invasion assays

    PMID:35719027

    Open questions at the time
    • No reconstitution of ABI2 inhibiting ABL1
    • Single Co-IP for the PRR16 interaction
  9. 2022 Low

    Reported a non-cytoskeletal nuclear role in which ABI2 recruits MEOX2 to activate KLF4/NANOG transcription and maintain HCC cancer stem-cell properties.

    Evidence Co-IP, ChIP of MEOX2 at KLF4/NANOG promoters, knockdown/overexpression and xenograft

    PMID:36017822

    Open questions at the time
    • No reconstitution of the ABI2-MEOX2 transcriptional complex
    • Mechanism of ABI2 nuclear function unresolved
  10. 2024 Low

    Extended the transcriptional-coactivator model, reporting ABI2 partnering with HHEX to upregulate SLC17A9 in HCC stem-like cells.

    Evidence Co-IP, reporter assay, ChIP and gene perturbation

    PMID:38844969

    Open questions at the time
    • No in vitro reconstitution
    • Relationship to cytoskeletal ABI2 functions unclear
  11. 2024 Low

    Described ABI2 interaction with RAC1 linked to PI3K/Akt suppression and identified CBLC as an E3 ligase driving ABI2 proteasomal degradation, adding a turnover input to ABI2 regulation.

    Evidence Co-IP, RNA-seq, siRNA, ubiquitination assay and Western blotting

    PMID:38937761

    Open questions at the time
    • Single Co-IP for the RAC1 interaction
    • Mechanism linking ABI2 to PI3K/Akt not established
  12. 2020 Medium

    Showed ABI2 is a direct target of EBV-miR-BART13-3p and that its loss drives NPC migration/EMT via c-JUN/SLUG, positioning ABI2 as a migration suppressor in this context.

    Evidence Luciferase 3'UTR reporter, siRNA plus overexpression rescue, migration/invasion assays and xenograft

    PMID:31907338

    Open questions at the time
    • Molecular link from ABI2 to c-JUN/SLUG not defined
    • Cytoskeletal versus transcriptional basis of suppression not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ABI2's well-established WRC/actin-regulatory function mechanistically relates to its reported nuclear transcriptional-coactivator roles, and how the competing kinase (PIM1, Pak2, Abl, Cdk5) and degradation (CBLC) inputs are integrated, remains unresolved.
  • No structural model of ABI2 within the WRC
  • Nuclear and cytoplasmic functions not reconciled in one system
  • Integration of opposing stabilizing and degradative signals undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 2 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 1 GO:0005856 cytoskeleton 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 1
Partners
ABL1CBLCHHEXMEOX2PIM1PRR16RAC1WAVE2
Complex memberships
WAVE regulatory complex (WRC)

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 ABI2 (Abi-2) was identified as a protein that binds specifically to both the SH3 domain and carboxy-terminal sequences of c-Abl tyrosine kinase in vitro and in vivo; ABI2 contains proline-rich sequences critical for binding the Abl SH3 domain, and ABI2 is a substrate for c-Abl tyrosine kinase phosphorylation. Expression of an ABI2 mutant lacking the Abl SH3-binding sequences but retaining carboxyl-terminus binding activated c-Abl transforming capacity. Yeast two-hybrid screen, in vitro binding assay, in vivo co-immunoprecipitation, kinase substrate assay, mutant overexpression Genes & development High 7590236
2000 Abi-2 protein is concentrated in puncta throughout the cell body and processes of cultured neurons, and is present in synaptosomes and growth cone particles, consistent with a role in Abl kinase signaling at synapses and growth cones in the developing nervous system. Abi proteins from brain lysates undergo changes in apparent molecular weight and phosphorylation with increasing age. Immunofluorescence in cultured neurons, subcellular fractionation (synaptosome and growth cone particle isolation), Western blotting Molecular and cellular neurosciences Medium 10995551
2004 Homozygous deletion of murine Abi2 causes defective secondary lens fiber cell migration and orientation in the eye, cell migration defects in the neocortex and hippocampus, abnormal dendritic spine morphology and density, and severe deficits in short- and long-term memory. Abi2 localizes to adherens junctions in the developing lens and at nascent epithelial cell adherens junctions in vitro. RNAi-mediated Abi downregulation impaired adherens junction formation and correlated with downregulation of the WAVE actin-nucleation promoting factor. Knockout mouse (homozygous deletion), RNA interference, immunolocalization, behavioral assays (memory tests), live imaging Molecular and cellular biology High 15572692
2007 Phosphorylation of c-Abl at serines 637 and 638 by Pak2 kinase dramatically reduces (~90%) ABI2 binding to c-Abl's PxxP motif, establishing a mechanism whereby Pak2-mediated phosphorylation of c-Abl inhibits the ABI2 SH3 domain–c-Abl PxxP interaction. This phosphorylation simultaneously increases Crk binding to c-Abl and c-Abl-mediated Crk phosphorylation. In vitro kinase assay (Pak2 phosphorylation of c-Abl fragments), binding assay, site-directed mutagenesis (S637/638/639A and 3D mutants), co-immunoprecipitation Biochemistry High 18161990
2012 WAVE2-Abi2 complex regulates growth cone activity in migrating cortical neurons. Abl kinase and Cdk5 phosphorylate WAVE2 at tyrosine 150 and serine 137, regulating WAVE2-Abi2 activity, which controls the multipolar-to-bipolar transition and initiation of glia-guided radial migration. Neurons lacking proper WAVE2-Abi2 function are mispositioned in the neocortex. Time-lapse imaging (lattice assays), phosphorylation-site mutagenesis of WAVE2, in vivo cortical positioning analysis Cerebral cortex Medium 22617848
2016 TIS21/BTG2 inhibits ABI2-DRF (diaphanous-related formin) pathway by reducing ABI2 protein stability and DRF expression, thereby downregulating doxorubicin-induced stress fiber formation and thick vimentin networks. This occurs downstream of Nox4-derived ROS, placing ABI2 in a Nox4-ROS-ABI2-DRF signal cascade controlling linear actin nucleation. Cell-based overexpression/knockdown, super-resolution STED microscopy, Western blotting, ROS measurement Cellular signalling Low 27932314
2023 PIM1 kinase phosphorylates ABI2 at Ser183, increasing ABI2 protein levels and enhancing WAVE regulatory complex (WRC) formation, resulting in increased protrusive activity and cell motility. Hypoxia-induced and PIM1-induced cell protrusion was dependent on ABI2. In vivo smooth muscle invasion assays showed PIM1 overexpression increased tumor invasion depth, and PIM inhibitors reduced invasion. Unbiased proteomic screen (PIM1 substrate identification), in vitro kinase assay, phospho-site mutagenesis (Ser183), co-immunoprecipitation (WRC formation), cell protrusion assays, in vivo invasion assay, PIM inhibitor treatment The Journal of cell biology High 37042842
2022 PRR16/Largen binds to ABI2 (identified by co-immunoprecipitation/pulldown screen), and knockdown of ABI2 or overexpression of PRR16 both increase ABL1 kinase phosphorylation at Y412, suggesting ABI2 normally inhibits ABL1 kinase activity; PRR16 binding to ABI2 interferes with this inhibition to promote EMT. Co-immunoprecipitation/binding protein screen, gene silencing (siRNA), Western blotting (ABL1 Y412 phosphorylation), migration/invasion assays Biomolecules & therapeutics Low 35719027
2024 ABI2 interacts with RAC1 (Rho GTPase) as shown by co-immunoprecipitation, and this interaction is associated with inhibition of the PI3K/Akt signaling pathway. E3 ubiquitin ligase CBLC promotes ubiquitination and proteasomal degradation of ABI2 protein. Co-immunoprecipitation, RNA-seq, siRNA knockdown, ubiquitination assay, Western blotting Cancer cell international Low 38937761
2024 ABI2 serves as a co-activator of the transcription factor HHEX, and together they upregulate SLC17A9 transcription to promote HCC cancer stem cell-like properties. Co-immunoprecipitation, reporter assay, ChIP, gene knockdown/overexpression Journal of translational medicine Low 38844969
2022 ABI2 recruits and directly interacts with the transcription factor MEOX2, which then binds to KLF4 and NANOG promoter regions to activate their transcription, thereby maintaining HCC cancer stem cell properties. Co-immunoprecipitation, ChIP (MEOX2 binding to KLF4/NANOG promoters), gene overexpression/knockdown, xenograft assay Liver international Low 36017822
2020 EBV-miR-BART13-3p directly targets the ABI2 3'UTR to downregulate ABI2 expression, and ABI2 silencing alone recapitulates increased NPC cell migration/invasion and EMT via activation of c-JUN/SLUG signaling; reconstitution of ABI2 reverses this phenotype. Luciferase 3'UTR reporter assay (direct miRNA targeting), siRNA silencing, overexpression rescue, migration/invasion assays, in vivo xenograft Aging Medium 31907338

Source papers

Stage 0 corpus · 32 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 The ABI1 and ABI2 protein phosphatases 2C act in a negative feedback regulatory loop of the abscisic acid signalling pathway. The Plant journal : for cell and molecular biology 449 11208021
2001 Abscisic acid activation of plasma membrane Ca(2+) channels in guard cells requires cytosolic NAD(P)H and is differentially disrupted upstream and downstream of reactive oxygen species production in abi1-1 and abi2-1 protein phosphatase 2C mutants. The Plant cell 382 11701885
2004 Paraptosis: mediation by MAP kinases and inhibition by AIP-1/Alix. Cell death and differentiation 317 15195070
2003 A novel domain in the protein kinase SOS2 mediates interaction with the protein phosphatase 2C ABI2. Proceedings of the National Academy of Sciences of the United States of America 272 14504388
1995 Abi-2, a novel SH3-containing protein interacts with the c-Abl tyrosine kinase and modulates c-Abl transforming activity. Genes & development 248 7590236
2017 Abscisic Acid Signaling Inhibits Brassinosteroid Signaling through Dampening the Dephosphorylation of BIN2 by ABI1 and ABI2. Molecular plant 135 29275167
2001 The sensitivity of ABI2 to hydrogen peroxide links the abscisic acid-response regulator to redox signalling. Planta 133 11882947
2004 ABI2-deficient mice exhibit defective cell migration, aberrant dendritic spine morphogenesis, and deficits in learning and memory. Molecular and cellular biology 123 15572692
2000 Localization and phosphorylation of Abl-interactor proteins, Abi-1 and Abi-2, in the developing nervous system. Molecular and cellular neurosciences 63 10995551
2009 AIP-1 ameliorates beta-amyloid peptide toxicity in a Caenorhabditis elegans Alzheimer's disease model. Human molecular genetics 49 19414486
2022 ABI2-mediated MEOX2/KLF4-NANOG axis promotes liver cancer stem cell and drives tumour recurrence. Liver international : official journal of the International Association for the Study of the Liver 33 36017822
2002 In search of a function for the E3B1/Abi2/Argbp1/NESH family (Review). International journal of molecular medicine 31 12011975
2020 Downregulation of ABI2 expression by EBV-miR-BART13-3p induces epithelial-mesenchymal transition of nasopharyngeal carcinoma cells through upregulation of c-JUN/SLUG signaling. Aging 24 31907338
2021 TMK4 receptor kinase negatively modulates ABA signaling by phosphorylating ABI2 and enhancing its activity. Journal of integrative plant biology 19 33811744
2010 skn-1-Dependent and -independent regulation of aip-1 expression following metabolic stress in Caenorhabditis elegans. Molecular and cellular biology 19 20351174
2012 WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration. Cerebral cortex (New York, N.Y. : 1991) 17 22617848
2007 Phosphorylation of c-Abl by protein kinase Pak2 regulates differential binding of ABI2 and CRK. Biochemistry 15 18161990
2017 A Novel RNA-Binding Protein Involves ABA Signaling by Post-transcriptionally Repressing ABI2. Frontiers in plant science 13 28174577
2023 PIM1 phosphorylates ABI2 to enhance actin dynamics and promote tumor invasion. The Journal of cell biology 12 37042842
2022 PRR16/Largen Induces Epithelial-Mesenchymal Transition through the Interaction with ABI2 Leading to the Activation of ABL1 Kinase. Biomolecules & therapeutics 10 35719027
2020 Association of Abl interactor 2, ABI2, with platelet/lymphocyte ratio in patients with renal cell carcinoma: A pilot study. International journal of experimental pathology 6 32496656
2016 TIS21/BTG2 inhibits doxorubicin-induced stress fiber-vimentin networks via Nox4-ROS-ABI2-DRF-linked signal cascade. Cellular signalling 6 27932314
2022 Na-AIP-1 secreted by human hookworms suppresses collagen-induced arthritis. Inflammopharmacology 5 35031905
2020 miR-25 expression is upregulated in pancreatic ductal adenocarcinoma and promotes cell proliferation by targeting ABI2. Experimental and therapeutic medicine 5 32266037
2024 The HHEX-ABI2/SLC17A9 axis induces cancer stem cell-like properties and tumorigenesis in HCC. Journal of translational medicine 4 38844969
2024 Inhibition of ABI2 ubiquitination-dependent degradation suppresses TNBC cell growth via down-regulating PI3K/Akt signaling pathway. Cancer cell international 3 38937761
2025 The role of ABI2 in modulating nuclear proteins: Therapeutic implications for NUP54 and NUP153 in TNBC. Advances in protein chemistry and structural biology 2 39843146
2025 Ethylene antagonizes ABA responses in stomatal movement and seed germination by upregulating ABI1 and ABI2 at both the transcript and protein levels. The Plant journal : for cell and molecular biology 2 40811817
2013 Age and dark rearing bidirectionally regulate the level and laminar pattern of expression of Abelson interacting protein 2 (Abi-2): a novel candidate visual cortical plasticity gene. Journal of molecular neuroscience : MN 1 23828391
2026 StWRKY46 promotes stomatal closure and enhances potato drought tolerance by mediating the PYL1-ABI2-OST1/SnRK2.5/SnRK2.6 pathway. Plant physiology 0 42090565
2025 Missense ABI2 variants linked to a neurodevelopmental disorder with intellectual disability, epilepsy, hypoplasia of the corpus callosum, and white matter abnormalities. medRxiv : the preprint server for health sciences 0 40475134
2025 Arsenic Sulfide Induces Apoptosis in Myelodysplastic Neoplasm Cells Through the Suppression of ABI2. Biological procedures online 0 41366287

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