Abi2 (Abl interactor 2) is a non-catalytic adaptor of the ABI family and a core subunit of the WAVE regulatory complex (WRC; WAVE/SCAR, CYFIP/SRA1, NCKAP1/NAP1, ABI and BRK1/HSPC300). Within the WRC, the N-terminal helical region of Abi2 forms a four-helix bundle with WAVE and HSPC300 that packs against the SRA1:NAP1 dimer, and its C-terminal SH3 domain binds Abl-family tyrosine kinases. Through the WRC, Abi2 couples Rac1 and membrane-receptor signals to Arp2/3-mediated branched actin nucleation at the tips of lamellipodia and filopodia, driving protrusion, cell migration and formation of nascent adherens junctions. Abi2 also promotes c-Abl-mediated phosphorylation of Mena/ENAH and WAVE2. Abi2 is expressed highly in brain and eye; Abi2-null mice show defective secondary lens fiber orientation and migration, neuronal migration defects in neocortex and hippocampus, altered dendritic spine morphology and density, and severe short- and long-term memory deficits. In human cells, ABI2-containing WAVE2 complexes are recruited to damaged mitochondria and contribute to actin-dependent mitophagy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000423 mitophagy | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Mitophagy, transferred from human ABI2 (IDA, PMID:38081847). Reason: In human cells, PINK1/Parkin-dependent phosphorylation of GRAF1 recruits ABI2 and assembles the WAVE2 complex on damaged mitochondria, where Arp2/3-dependent branched actin is needed for mitochondrial clearance. ABI2 therefore does part of the work as a WRC subunit supplying actin-nucleation-promoting activity to this process. This is a context-specific deployment of its general WRC role, so it is retained as non-core; there is no mouse-specific evidence yet. The human ABI2 review of the source IDA row was harmonized to the same action (it had marked the row over-annotated because ABI2 itself was not depleted; ABI2 is nonetheless the WRC subunit bound directly by phospho-GRAF1). Supporting Evidence: PMID:38081847 In turn, 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:0001764 neuron migration | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Neuron migration, inferred phylogenetically from ABI family members including mouse Abi2 itself. Reason: Abi2-null mice show migration defects of neocortical and hippocampal neurons (PMID:15572692), and Abi2 overexpression rescues cortical radial migration in PcdhΞ± knockdown neurons (PMID:29911975). The WRC drives the leading-edge protrusion that migrating neurons use, so participation is plausible. Neuron migration is one cell-type-specific instance of the WRC role in cell migration, so it is kept as non-core. Supporting Evidence: PMID:15572692 Loss of Abi2 also resulted in cell migration defects in the neocortex and hippocampus, abnormal dendritic spine morphology and density, and severe deficits in short- and long-term memory. PMID:29911975 Remarkably, we found that overexpression of either WAVE2 (Wasf2) or Abi2 in vivo rescues the cortical neuron migration defect of Ξ±KD neurons (Figure 2B) although they themselves have no apparent influence on cortical neuron migration (Figure 2C). |
| GO:0001764 neuron migration | IDA PMID:29911975 Alpha protocadherins and Pyk2 kinase regulate cortical neuro... | KEEP AS NON CORE | Summary: Neuron migration, from in utero electroporation experiments in which Abi2 overexpression rescued cortical neuron migration after PcdhΞ± knockdown. Reason: Overexpressed Abi2 (like WAVE2) rescues the radial-migration defect of PcdhΞ±-knockdown cortical neurons, supporting a PcdhΞ±βWAVE complex axis in migration. This is a rescue experiment, not a loss-of-function test of Abi2 itself, but together with the Abi2-null migration phenotype (PMID:15572692) it is consistent. Non-core, cell-type-specific. Supporting Evidence: PMID:29911975 Remarkably, we found that overexpression of either WAVE2 (Wasf2) or Abi2 in vivo rescues the cortical neuron migration defect of Ξ±KD neurons (Figure 2B) although they themselves have no apparent influence on cortical neuron migration (Figure 2C). PMID:15572692 Loss of Abi2 also resulted in cell migration defects in the neocortex and hippocampus, abnormal dendritic spine morphology and density, and severe deficits in short- and long-term memory. |
| GO:0005634 nucleus | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Nucleus, transferred from human ABI2. Reason: The human source of this row is not the Human Protein Atlas. In genes/human/ABI2/ABI2-goa.tsv, GO:0005634 nucleus is IEA from GO_REF:0000044 via the UniProt subcellular-location keyword UniProtKB-SubCell:SL-0191 (line 8); the HPA immunofluorescence IDA (GO_REF:0000052, line 126) supports GO:0005654 nucleoplasm instead. So the mouse row is an ISO transfer of a keyword-derived electronic assertion, with no experimental nuclear localization of ABI2 behind it in either species. The nucleocytoplasmic-shuttling literature in this family concerns the ABI1 paralog, and no nuclear function has been established for ABI2; its localization set is actin-rich and junctional. Over-annotated rather than a genuine minor site. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:Q9NYB9 Β· ABI2 SOURCE WEAK OR INFERRED Human ABI2 GO:0005634 is itself IEA (GO_REF:0000044) from the UniProtKB-SubCell:SL-0191 keyword, not an experimental localization; the HPA IDA row supports nucleoplasm, not nucleus. Supporting Evidence: file:mouse/Abi2/Abi2-deep-research-falcon.md Abi2 exhibits a characteristic localization pattern to sites of dynamic actin reorganization and cell-cell contact file:mouse/Abi2/Abi2-deep-research-falcon.md Abl interactor 1 (abi-1) wave-binding and snare domains regulate its nucleocytoplasmic shuttling, lamellipodium localization, and wave-1 levels. |
| GO:0005654 nucleoplasm | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Nucleoplasm, transferred from human ABI2 (HPA immunofluorescence). Reason: This, not the nucleus row, is the one whose human source is the Human Protein Atlas IDA (GO_REF:0000052, genes/human/ABI2/ABI2-goa.tsv line 126), a large-scale antibody-based screen rather than a targeted study of ABI2 localization. No nuclear function has been established for ABI2, and the deep research records no nuclear site for it; the nuclear material in this family is on the ABI1 paralog. An ISO transfer of a single high-throughput immunofluorescence call is over-annotation for mouse Abi2. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:Q9NYB9 Β· ABI2 SOURCE WEAK OR INFERRED Human ABI2 GO:0005654 rests on one HPA immunofluorescence IDA (GO_REF:0000052) with no corroborating ABI2-specific nuclear study. Supporting Evidence: file:mouse/Abi2/Abi2-deep-research-falcon.md Abi2 exhibits a characteristic localization pattern to sites of dynamic actin reorganization and cell-cell contact |
| GO:0005737 cytoplasm | ISO GO_REF:0000119 | ACCEPT | Summary: Cytoplasm, transferred from human ABI2. Reason: ABI2 is a soluble cytoplasmic adaptor that is recruited to protrusion tips and cell junctions as part of the WRC. Correct, broad localization. Supporting Evidence: PMID:11516653 We show that Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited to the tips of lamellipodia and filopodia. |
| GO:0005829 cytosol | ISO GO_REF:0000119 | ACCEPT | Summary: Cytosol, transferred from human ABI2. Reason: The WRC is held basally inactive in the cytosol and recruited to membranes by Rac1 and membrane receptors, so a soluble resting pool is the premise of the recruitment step that PMID:21107423 maps structurally. Note the one fractionation observation in the folder points the other way (Abi2 is largely insoluble in hypotonic buffers), so cytosol is accepted as a resting compartment rather than a site of action. Supporting Evidence: PMID:21107423 The polybasic region of WAVE2 (equivalent to residues 172-184 of WAVE1) can bind phosphoinositide lipids in vitro, and is essential for membrane recruitment of the WRC and formation of lamellipodia in cells file:mouse/Abi2/Abi2-deep-research-falcon.md Biochemically, Abi2 associates with membrane-cytoskeletal fractions, being largely insoluble in hypotonic buffers but extractable with detergent-containing RIPA buffer, consistent with membrane-associated cytoskeletal localization |
| GO:0005829 cytosol | ISO PMID:17101133 NESH (Abi-3) is present in the Abi/WAVE complex but does not... | ACCEPT | Summary: Cytosol, from the human ortholog, based on the study of Abi family proteins in the Abi/WAVE complex. Reason: Consistent with ABI2 being a cytoplasmic WRC subunit. Supporting Evidence: PMID:17101133 Our results suggest that NESH (Abi-3), like Abi-1 and Abi-2, is a component of the Abi/WAVE complex, but likely plays a different role in the regulation of c-Abl. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoskeleton, mapped from the UniProt subcellular location. Reason: ABI2 is concentrated at sites of actin polymerization (lamellipodium and filopodium tips), where it works with the actin cytoskeleton. Correct, if broad. Supporting Evidence: PMID:11516653 We show that Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited to the tips of lamellipodia and filopodia. |
| GO:0005884 actin filament | ISO GO_REF:0000119 | ACCEPT | Summary: Colocalizes with actin filaments, from human ABI2. Reason: Abi proteins concentrate at the tips of F-actin-rich lamellipodia and filopodia and at the tips of F-actin protrusions at nascent adherens junctions. The colocalizes_with qualifier is appropriate because ABI2 does not bind F-actin directly. Supporting Evidence: PMID:11516653 We show that Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited to the tips of lamellipodia and filopodia. |
| GO:0005884 actin filament | ISS GO_REF:0000024 | ACCEPT | Summary: Colocalizes with actin filaments, transferred by curator judgment from human ABI2. Reason: Same basis as the ISO row; colocalization rather than direct binding is the correct claim. Supporting Evidence: PMID:11516653 We show that Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited to the tips of lamellipodia and filopodia. |
| GO:0005912 adherens junction | IDA PMID:15572692 ABI2-deficient mice exhibit defective cell migration, aberra... | KEEP AS NON CORE | Summary: Adherens junction, from immunolocalization of Abi2 in the developing lens and at nascent epithelial adherens junctions. Reason: Grove et al. show directly that Abi2 is enriched at forming adherens junctions and decreases as they mature. This is a real, experimentally supported localization, but a secondary site of WRC action relative to the leading edge, so it is kept as non-core. Supporting Evidence: PMID:15572692 Here we showed that Abi2 is enriched at adherens junctions and that as adherens junctions mature, Abi2 accumulation diminishes at these sites. |
| GO:0005912 adherens junction | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Adherens junction, mapped from the UniProt subcellular location (itself based on PMID:15572692). Reason: Same basis as the IDA row. Non-core. Supporting Evidence: PMID:15572692 Here we showed that Abi2 is enriched at adherens junctions and that as adherens junctions mature, Abi2 accumulation diminishes at these sites. |
| GO:0005912 adherens junction | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Adherens junction, from human ABI2. Reason: Consistent with the mouse IDA data (PMID:15572692). Non-core. Supporting Evidence: PMID:15572692 Here we showed that Abi2 is enriched at adherens junctions and that as adherens junctions mature, Abi2 accumulation diminishes at these sites. |
| GO:0005912 adherens junction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Adherens junction, from human ABI2 by curator judgment. Reason: Consistent with the mouse IDA data (PMID:15572692). Non-core. Supporting Evidence: PMID:15572692 Here we showed that Abi2 is enriched at adherens junctions and that as adherens junctions mature, Abi2 accumulation diminishes at these sites. |
| GO:0007611 learning or memory | IMP PMID:15572692 ABI2-deficient mice exhibit defective cell migration, aberra... | KEEP AS NON CORE | Summary: Learning or memory, from behavioral testing of Abi2-deficient mice. Reason: Abi2 knockout mice have severe short- and long-term memory deficits, accompanied by abnormal dendritic spine morphology and density. The deficit is a distant organism-level consequence of disrupted actin remodeling in spines; the annotation is acceptable with the acts_upstream_of_or_within qualifier but is not a core function. Supporting Evidence: PMID:15572692 These mice exhibited highly penetrant and profound impairments in short- and long-term memory. PMID:15572692 We showed that basal dendrites of layer III pyramidal neurons of Abi2-deficient mice exhibited a significant decrease in the relative proportion of mushroom-shaped spines and a corresponding increase in the proportion of stubby spines. |
| GO:0010592 positive regulation of lamellipodium assembly | ISO GO_REF:0000119 | ACCEPT | Summary: Positive regulation of lamellipodium assembly, from human ABI2. Reason: Lamellipodium formation is the main cellular output of the WRC, and ABI2 is a structural subunit of the WAVE1:ABI2:HSPC300 trimer. Abi proteins sit at lamellipodium tips, and knocking down Abi lowers WAVE levels (PMID:15572692). Core. Supporting Evidence: PMID:21107423 MiniWRC can be delineated into two subcomplexes: an Sra1:Nap1 dimer and a WAVE1:Abi2:HSPC300 trimer PMID:11516653 We show that Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited to the tips of lamellipodia and filopodia. PMID:15572692 Downregulation of Abi expression by RNA interference impaired adherens junction formation and correlated with downregulation of the Wave actin-nucleation promoting factor. |
| GO:0016358 dendrite development | IMP PMID:15572692 ABI2-deficient mice exhibit defective cell migration, aberra... | MARK AS OVER ANNOTATED | Summary: Dendrite development, from the Abi2 knockout. Reason: The knockout phenotype that was actually measured concerns dendritic spines (fewer mushroom spines, more stubby spines, lower spine density), not dendrite arborization or dendrite outgrowth in general. The more specific annotation, regulation of dendritic spine morphogenesis (GO:0061001), from the same paper captures the finding better; the broad dendrite development term overstates it. Supporting Evidence: PMID:15572692 We showed that basal dendrites of layer III pyramidal neurons of Abi2-deficient mice exhibited a significant decrease in the relative proportion of mushroom-shaped spines and a corresponding increase in the proportion of stubby spines. PMID:15572692 Moreover, spine density on apical dendritic branches of layer V pyramidal cells and in the CA1 region of the hippocampus was significantly reduced in Abi2-deficient mice compared to wild-type mice. |
| GO:0016477 cell migration | IMP PMID:15572692 ABI2-deficient mice exhibit defective cell migration, aberra... | ACCEPT | Summary: Cell migration, from the Abi2 knockout (lens fiber and neuronal migration defects). Reason: Abi2-null mice have defective migration of secondary lens fibers and of neocortical and hippocampal neurons. As a WRC subunit ABI2 contributes directly to the lamellipodial protrusion that drives migration. This is a central process for the gene. Supporting Evidence: PMID:15572692 In the absence of Abi2, secondary lens fiber orientation and migration were defective in the eye, without detectable defects in proliferation, differentiation, or apoptosis. PMID:15572692 Loss of Abi2 also resulted in cell migration defects in the neocortex and hippocampus, abnormal dendritic spine morphology and density, and severe deficits in short- and long-term memory. |
| GO:0016601 Rac protein signal transduction | ISO GO_REF:0000119 | ACCEPT | Summary: Rac protein signal transduction, from human ABI2. Reason: The WRC is the principal Rac1 effector for Arp2/3 activation. Rac1-GTP binds CYFIP/SRA1 and releases the WAVE VCA region, and ABI2 is an integral subunit of the trimer that carries WAVE. ABI2 is part of the effector machinery of this pathway. Core. Supporting Evidence: PMID:21107423 MiniWRC can be delineated into two subcomplexes: an Sra1:Nap1 dimer and a WAVE1:Abi2:HSPC300 trimer PMID:15572692 We propose that the absence of Abi2 results in defects in Rac-dependent pathways involved in the regulation of actin dynamics, producing deficits in spine morphology and density. |
| GO:0030027 lamellipodium | IBA GO_REF:0000033 | ACCEPT | Summary: Lamellipodium, phylogenetic inference across the ABI family. Reason: Abi-2 fused to EYFP is recruited to the tips of lamellipodia, and the ABI family localization is conserved from Dictyostelium and Drosophila to mammals. Core localization. Supporting Evidence: PMID:11516653 We show that Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited to the tips of lamellipodia and filopodia. |
| GO:0030027 lamellipodium | IEA GO_REF:0000044 | ACCEPT | Summary: Lamellipodium, mapped from the UniProt subcellular location. Reason: Supported by direct localization of EYFP-Abi-2b at lamellipodium tips. Supporting Evidence: PMID:11516653 We show that Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited to the tips of lamellipodia and filopodia. |
| GO:0030027 lamellipodium | ISO GO_REF:0000119 | ACCEPT | Summary: Lamellipodium, from human ABI2. Reason: Supported by direct localization of EYFP-Abi-2b at lamellipodium tips. Supporting Evidence: PMID:11516653 We show that Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited to the tips of lamellipodia and filopodia. |
| GO:0030175 filopodium | IEA GO_REF:0000044 | ACCEPT | Summary: Filopodium, mapped from the UniProt subcellular location. Reason: EYFP-Abi-2b is recruited to filopodium tips. Supporting Evidence: PMID:11516653 We show that Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited to the tips of lamellipodia and filopodia. |
| GO:0030425 dendrite | IDA PMID:15572692 ABI2-deficient mice exhibit defective cell migration, aberra... | KEEP AS NON CORE | Summary: Dendrite, from immunolocalization in mouse brain. Reason: Abi2 is detected in dendritic spines (and axons) of mouse neurons. The dendrite localization is correct but neuron-specific, and the more specific dendritic spine annotation captures it better. Non-core. Supporting Evidence: PMID:15572692 Abi2 was expressed in both axons and dendritic spines. |
| GO:0031209 SCAR complex | IBA GO_REF:0000033 | ACCEPT | Summary: SCAR complex, phylogenetic inference across ABI/SCAR-complex orthologs from Dictyostelium to mammals. Reason: ABI2 is a structural subunit of the WAVE regulatory complex. The WRC crystal structure was solved with Abi2 as the ABI subunit, forming a four-helix bundle with WAVE1 and HSPC300. Core. Supporting Evidence: PMID:21107423 MiniWRC can be delineated into two subcomplexes: an Sra1:Nap1 dimer and a WAVE1:Abi2:HSPC300 trimer 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:0031209 SCAR complex | ISO GO_REF:0000119 | ACCEPT | Summary: SCAR complex, from human ABI2. Reason: Structurally established WRC subunit. Supporting Evidence: PMID:21107423 MiniWRC can be delineated into two subcomplexes: an Sra1:Nap1 dimer and a WAVE1:Abi2:HSPC300 trimer PMID:17101133 Our results suggest that NESH (Abi-3), like Abi-1 and Abi-2, is a component of the Abi/WAVE complex, but likely plays a different role in the regulation of c-Abl. |
| GO:0031267 small GTPase binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Small GTPase binding (contributes_to), from human ABI2. Reason: Rac1-GTP binds the WRC mainly through CYFIP/SRA1, not ABI2 directly. The contributes_to qualifier correctly frames this as a complex-level activity to which ABI2 contributes structurally, as part of the WAVE:ABI:HSPC300 trimer that packs against SRA1. The complex-level claim is acceptable; it is not ABI2's own activity and is kept as non-core. 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:0031625 ubiquitin protein ligase binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Ubiquitin protein ligase binding, from human ABI2 (TRIM32 interaction). Reason: The E3 ligase TRIM32 binds and ubiquitinates ABI2, leading to its degradation. This binding reflects ABI2 being a ligase substrate (regulation of ABI2 turnover) rather than a function ABI2 performs. It is correct as an interaction, but it is not a core function. Supporting Evidence: PMID:18632609 we found by using yeast two-hybrid screening that TRIM32 binds to Abl-interactor 2 (Abi2), which is known as a tumor suppressor and a cell migration inhibitor, and we showed that TRIM32 mediates the ubiquitination of Abi2. |
| GO:0032433 filopodium tip | ISO GO_REF:0000119 | ACCEPT | Summary: Filopodium tip, from human ABI2. Reason: EYFP-Abi-2b is recruited to the tips of filopodia, the sites of actin assembly. Supporting Evidence: PMID:11516653 We show that 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 | IBA GO_REF:0000033 | ACCEPT | Summary: Signaling adaptor activity, phylogenetic inference within the ABI family. Reason: ABI2 has no catalytic activity. It uses its N-terminal helical/HHR region to assemble into the WRC and its C-terminal SH3 domain to bind Abl-family kinases, coupling upstream signals (Rac, Abl, membrane receptors) to WAVE-driven Arp2/3 activation. Abi-2 promotes c-Abl-mediated phosphorylation of Mena and WAVE2, consistent with an adaptor role. This is the best available MF term for ABI2. Supporting Evidence: PMID:17101133 Although Abi-2, like Abi-1, promoted the c-Abl-mediated phosphorylation of Mena and WAVE2, NESH (Abi-3) had no such effect. 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 file:mouse/Abi2/Abi2-deep-research-falcon.md Abi2 functions as a **non-enzymatic adaptor and scaffold protein** within the WAVE regulatory complex (WRC). |
| GO:0035591 signaling adaptor activity | ISO GO_REF:0000119 | ACCEPT | Summary: Signaling adaptor activity, from human ABI2. Reason: Same basis as the IBA row. Supporting Evidence: PMID:17101133 Although Abi-2, like Abi-1, promoted the c-Abl-mediated phosphorylation of Mena and WAVE2, NESH (Abi-3) had no such effect. PMID:21107423 MiniWRC can be delineated into two subcomplexes: an Sra1:Nap1 dimer and a WAVE1:Abi2:HSPC300 trimer |
| GO:0042802 identical protein binding | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Identical protein binding, from human ABI2 high-throughput interactome data. Reason: Human ABI2 self-association comes only from high-throughput interaction screens. In the WRC, ABI2 is present as a single subunit within the WAVE:ABI:HSPC300 trimer, and no functional homo-oligomerization of ABI2 has been characterized. The annotation says nothing about function and overstates what screening data supports. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q9NYB9 Β· ABI2 SOURCE WEAK OR INFERRED Human ABI2 self-binding rests on high-throughput interactome IPI rows (PMID:25416956, PMID:29892012), with no characterized ABI2 homo-oligomer. Supporting Evidence: PMID:21107423 MiniWRC can be delineated into two subcomplexes: an Sra1:Nap1 dimer and a WAVE1:Abi2:HSPC300 trimer |
| GO:0043010 camera-type eye development | IMP PMID:15572692 ABI2-deficient mice exhibit defective cell migration, aberra... | KEEP AS NON CORE | Summary: Camera-type eye development, from the Abi2 knockout lens phenotype. Reason: Abi2-null mice have defective orientation and migration of secondary lens fibers, giving an anterior lens gap. This is a real phenotype. The more specific lens fiber cell morphogenesis term from the same paper captures it better, and eye development is a tissue-level consequence of the WRC role. Non-core. Supporting Evidence: PMID:15572692 In the absence of Abi2, secondary lens fiber orientation and migration were defective in the eye, without detectable defects in proliferation, differentiation, or apoptosis. |
| GO:0043197 dendritic spine | IDA PMID:15572692 ABI2-deficient mice exhibit defective cell migration, aberra... | KEEP AS NON CORE | Summary: Dendritic spine, from immunolocalization in mouse brain. Reason: Abi2 is detected in dendritic spines, consistent with the spine morphology phenotype in knockouts. This is a correct but neuron-specific localization of the WRC; non-core. Supporting Evidence: PMID:15572692 Abi2 was expressed in both axons and dendritic spines. |
| GO:0043197 dendritic spine | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Dendritic spine, mapped from the UniProt subcellular location (based on PMID:15572692). Reason: Same basis as the IDA row. Supporting Evidence: PMID:15572692 Abi2 was expressed in both axons and dendritic spines. |
| GO:0045186 zonula adherens assembly | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Zonula adherens assembly, from human ABI2. Reason: RNAi depletion of Abi proteins impairs formation of nascent adherens junctions, and Abi2 accumulates at forming (not mature) junctions, consistent with WRC-driven lamellipodia helping to form junctions. ABI2 plausibly does part of the work by supplying WRC activity at the contact. Non-core. Note that the RNAi reduced Abi proteins in general, not only ABI2. Supporting Evidence: PMID:15572692 Downregulation of Abi expression by RNA interference impaired adherens junction formation and correlated with downregulation of the Wave actin-nucleation promoting factor. PMID:15572692 Here we showed that Abi2 is enriched at adherens junctions and that as adherens junctions mature, Abi2 accumulation diminishes at these sites. |
| GO:0045186 zonula adherens assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Zonula adherens assembly, from human ABI2 by curator judgment. Reason: Same basis as the ISO row. Supporting Evidence: PMID:15572692 Downregulation of Abi expression by RNA interference impaired adherens junction formation and correlated with downregulation of the Wave actin-nucleation promoting factor. PMID:15572692 Here we showed that Abi2 is enriched at adherens junctions and that as adherens junctions mature, Abi2 accumulation diminishes at these sites. |
| GO:0061001 regulation of dendritic spine morphogenesis | IMP PMID:15572692 ABI2-deficient mice exhibit defective cell migration, aberra... | KEEP AS NON CORE | Summary: Regulation of dendritic spine morphogenesis, from the Abi2 knockout. Reason: Abi2-null (and heterozygous) mice have fewer mushroom spines, more stubby spines and lower spine density. This is the best-supported neuronal process annotation for Abi2 and reflects WRC-driven actin remodeling in spines. It is neuron-specific, so it is non-core. Supporting Evidence: PMID:15572692 We showed that basal dendrites of layer III pyramidal neurons of Abi2-deficient mice exhibited a significant decrease in the relative proportion of mushroom-shaped spines and a corresponding increase in the proportion of stubby spines. PMID:15572692 Moreover, spine density on apical dendritic branches of layer V pyramidal cells and in the CA1 region of the hippocampus was significantly reduced in Abi2-deficient mice compared to wild-type mice. |
| GO:0061098 positive regulation of protein tyrosine kinase activity | ISO PMID:17101133 NESH (Abi-3) is present in the Abi/WAVE complex but does not... | KEEP AS NON CORE | Summary: Positive regulation of protein tyrosine kinase activity, from the human study comparing Abi family proteins. Reason: Abi-2, like Abi-1, promotes c-Abl-mediated phosphorylation of Mena and WAVE2, so ABI2 increases the substrate-directed output of ABL1. It is unclear whether this reflects stimulation of intrinsic kinase activity or adaptor-mediated substrate presentation, which fits the signaling adaptor MF better. Retained as non-core. Supporting Evidence: PMID:17101133 Although Abi-2, like Abi-1, promoted the c-Abl-mediated phosphorylation of Mena and WAVE2, NESH (Abi-3) had no such effect. |
| GO:0070309 lens fiber cell morphogenesis | IMP PMID:15572692 ABI2-deficient mice exhibit defective cell migration, aberra... | KEEP AS NON CORE | Summary: Lens fiber cell morphogenesis, from the Abi2 knockout. Reason: The most penetrant Abi2-null phenotype is incorrect orientation and migration of secondary lens fibers, with no change in proliferation, differentiation or survival. Abi2 localizes to the adherens junctions at the fiber tips. This is a specific, well-supported tissue role, but a deployment of the general WRC function; non-core. Supporting Evidence: PMID:15572692 In the absence of Abi2, secondary lens fiber orientation and migration were defective in the eye, without detectable defects in proliferation, differentiation, or apoptosis. PMID:15572692 Here we showed that Abi2 is enriched at adherens junctions and that as adherens junctions mature, Abi2 accumulation diminishes at these sites. |
| GO:0098858 actin-based cell projection | IBA GO_REF:0000033 | ACCEPT | Summary: Actin-based cell projection, phylogenetic inference. Reason: ABI2 localizes to the tips of lamellipodia and filopodia. Supporting Evidence: PMID:11516653 We show that Abi-1 and Abi-2b fused to enhanced yellow fluorescent protein (EYFP) are recruited to the tips of lamellipodia and filopodia. |
| GO:0098871 postsynaptic actin cytoskeleton | IDA PMID:15572692 ABI2-deficient mice exhibit defective cell migration, aberra... | KEEP AS NON CORE | Summary: Postsynaptic actin cytoskeleton (SynGO-style annotation), from localization of Abi2 in dendritic spines. Reason: Abi2 is present in dendritic spines, and loss of Abi2 alters spine morphology, consistent with action on the spine actin cytoskeleton. This is plausible but inferred largely from spine localization rather than fractionation of the postsynaptic cytoskeleton. Neuron-specific; non-core. Supporting Evidence: PMID:15572692 Abi2 was expressed in both axons and dendritic spines. PMID:15572692 We propose that the absence of Abi2 results in defects in Rac-dependent pathways involved in the regulation of actin dynamics, producing deficits in spine morphology and density. |
| GO:0098871 postsynaptic actin cytoskeleton | IMP PMID:15572692 ABI2-deficient mice exhibit defective cell migration, aberra... | KEEP AS NON CORE | Summary: Postsynaptic actin cytoskeleton, from the Abi2 knockout spine phenotype. Reason: A mutant phenotype is indirect evidence for a location, but the spine phenotype together with spine localization supports that Abi2 acts at the postsynaptic actin cytoskeleton. Non-core. Supporting Evidence: PMID:15572692 We showed that basal dendrites of layer III pyramidal neurons of Abi2-deficient mice exhibited a significant decrease in the relative proportion of mushroom-shaped spines and a corresponding increase in the proportion of stubby spines. PMID:15572692 Abi2 was expressed in both axons and dendritic spines. |
| GO:0098974 postsynaptic actin cytoskeleton organization | IDA PMID:15572692 ABI2-deficient mice exhibit defective cell migration, aberra... | KEEP AS NON CORE | Summary: Postsynaptic actin cytoskeleton organization, from the Abi2 knockout spine study. Reason: The authors propose that loss of Abi2 disrupts Rac-dependent actin dynamics in spines, giving the altered morphology and density. As a WRC subunit, Abi2 plausibly contributes Arp2/3 activation to spine actin organization. Neuron-specific; non-core. Supporting Evidence: PMID:15572692 We propose that the absence of Abi2 results in defects in Rac-dependent pathways involved in the regulation of actin dynamics, producing deficits in spine morphology and density. PMID:15572692 We showed that basal dendrites of layer III pyramidal neurons of Abi2-deficient mice exhibited a significant decrease in the relative proportion of mushroom-shaped spines and a corresponding increase in the proportion of stubby spines. |
| GO:0098974 postsynaptic actin cytoskeleton organization | IMP PMID:15572692 ABI2-deficient mice exhibit defective cell migration, aberra... | KEEP AS NON CORE | Summary: Postsynaptic actin cytoskeleton organization, from the Abi2 knockout. Reason: Same basis as the IDA row. Supporting Evidence: PMID:15572692 We propose that the absence of Abi2 results in defects in Rac-dependent pathways involved in the regulation of actin dynamics, producing deficits in spine morphology and density. PMID:15572692 Moreover, spine density on apical dendritic branches of layer V pyramidal cells and in the CA1 region of the hippocampus was significantly reduced in Abi2-deficient mice compared to wild-type mice. |
| GO:0098978 glutamatergic synapse | IDA PMID:15572692 ABI2-deficient mice exhibit defective cell migration, aberra... | KEEP AS NON CORE | Summary: Glutamatergic synapse, from localization of Abi2 in dendritic spines of cortical and hippocampal pyramidal neurons. Reason: The spines studied (pyramidal neurons, CA1) are predominantly excitatory glutamatergic synapses, so the annotation is reasonable. Neuron-specific; non-core. Supporting Evidence: PMID:15572692 Abi2 was expressed in both axons and dendritic spines. PMID:15572692 Moreover, spine density on apical dendritic branches of layer V pyramidal cells and in the CA1 region of the hippocampus was significantly reduced in Abi2-deficient mice compared to wild-type mice. |
| GO:0098978 glutamatergic synapse | IMP PMID:15572692 ABI2-deficient mice exhibit defective cell migration, aberra... | KEEP AS NON CORE | Summary: Glutamatergic synapse, from the Abi2 knockout spine phenotype. Reason: Same basis as the IDA row; mutant phenotype evidence for a location is indirect. Supporting Evidence: PMID:15572692 Moreover, spine density on apical dendritic branches of layer V pyramidal cells and in the CA1 region of the hippocampus was significantly reduced in Abi2-deficient mice compared to wild-type mice. |
| GO:0099173 postsynapse organization | IDA PMID:15572692 ABI2-deficient mice exhibit defective cell migration, aberra... | KEEP AS NON CORE | Summary: Postsynapse organization, from the Abi2 knockout spine study. Reason: Altered spine morphology and density in Abi2-deficient mice support a role in organizing postsynaptic structure through actin remodeling. Overlaps with the more specific postsynaptic actin cytoskeleton organization term. Non-core. Supporting Evidence: PMID:15572692 We showed that basal dendrites of layer III pyramidal neurons of Abi2-deficient mice exhibited a significant decrease in the relative proportion of mushroom-shaped spines and a corresponding increase in the proportion of stubby spines. |
| GO:0099173 postsynapse organization | IMP PMID:15572692 ABI2-deficient mice exhibit defective cell migration, aberra... | KEEP AS NON CORE | Summary: Postsynapse organization, from the Abi2 knockout. Reason: Same basis as the IDA row. Supporting Evidence: PMID:15572692 Moreover, spine density on apical dendritic branches of layer V pyramidal cells and in the CA1 region of the hippocampus was significantly reduced in Abi2-deficient mice compared to wild-type mice. |
| GO:2000601 positive regulation of Arp2/3 complex-mediated actin nucleation | ISO GO_REF:0000119 | ACCEPT | Summary: Positive regulation of Arp2/3 complex-mediated actin nucleation, from human ABI2. Reason: Activating Arp2/3 through the WAVE VCA region is the central biochemical output of the WRC, and ABI2 is a structural subunit of the WAVE:ABI:HSPC300 trimer that carries WAVE. Core. Supporting Evidence: PMID:21107423 MiniWRC can be delineated into two subcomplexes: an Sra1:Nap1 dimer and a WAVE1:Abi2:HSPC300 trimer 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 |
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Download this section (compressed HTML)Q: Does Abi2 act in dendritic spines as part of the canonical WRC, or does it have WRC-independent roles (e.g. via Abl kinases) at synapses? Abi1 is also expressed in brain, so how much redundancy is there?
Q: Is the ABI2 effect on ABL1-mediated phosphorylation of Mena/WAVE2 a true stimulation of kinase activity, or adaptor-mediated substrate recruitment? The answer decides whether "positive regulation of protein tyrosine kinase activity" is the right process term.
Experiment: Conditional (neuron-specific) Abi2 deletion combined with Abi1 deletion, with WRC-assembly-deficient versus SH3-deleted Abi2 rescue constructs, to separate WRC-dependent from Abl-dependent functions in spine morphogenesis and memory.
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