id: A0A8M3AND6 gene_symbol: abi1a product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:7955 label: Danio rerio description: abi1a (abl-interactor 1a) is one of two zebrafish co-orthologs of vertebrate ABI1, retained from the teleost-specific genome duplication; its paralog is abi1b. It encodes an ABI-family adaptor with an N-terminal WAVE-binding and coiled-coil region, a central proline-rich disordered region and a C-terminal SH3 domain. In mammals ABI1 is a core subunit of the WAVE regulatory complex (SCAR complex), which it assembles and activates to drive Arp2/3-dependent actin polymerization in lamellipodia, and its SH3 domain binds Abl kinases and other signalling partners. The zebrafish protein conserves the WAVE-binding N-terminus, the coiled-coil domain and the SH3 domain. abi1a is expressed at low levels maternally and becomes the predominant ABI1 copy from mid-gastrulation onward, with broad expression across larval and adult tissues. A mosaic F0 CRISPR knockdown did not disturb heart development; no other functional data exist for this copy. existing_annotations: - term: id: GO:0001764 label: neuron migration evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in supporting_entities: - MGI:MGI:106913 - PANTHER:PTN000825624 - WB:WBGene00015146 review: summary: Neuron migration propagated from PANTHER node PTN000825624, seeded by mouse Abi2 (MGI:106913) and a C. elegans ABI member. action: KEEP_AS_NON_CORE reason: The mouse evidence is for Abi2, whose knockout disturbs neuronal migration in neocortex and hippocampus. WAVE-complex-driven protrusion is a plausible general contributor to neuronal migration, and both zebrafish copies descend from the node, so the IBA is not wrong. It is not a core function of ABI1 (whose mouse knockout phenotype is embryonic heart and brain malformation), and nothing in zebrafish tests it. Kept as non-core; the same action is applied to abi1b. supported_by: - reference_id: PMID:15572692 supporting_text: 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. - reference_id: PMID:21482783 supporting_text: Thus, Abi1-signaling events are not required for gastrulation but are critical during brain and heart development. - term: id: GO:0005856 label: cytoskeleton evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0090 review: summary: Cytoskeleton location mapped from the UniProt subcellular-location vocabulary (ARBA rule). action: ACCEPT reason: ABI1 acts at the cortical actin cytoskeleton of protruding membranes as part of the WAVE complex. The term is general but correct; the more informative location is lamellipodium. supported_by: - reference_id: PMID:15048123 supporting_text: The WAVE2-Abi1-Nap1-PIR121 complex is as active as the WAVE2-Abi1 sub-complex in stimulating Arp2/3, and after Rac activation it is re-localized to the leading edge of ruffles in vivo. - term: id: GO:0030027 label: lamellipodium evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in supporting_entities: - FB:FBgn0020510 - MGI:MGI:104913 - MGI:MGI:1913860 - PANTHER:PTN000048906 - UniProtKB:Q8IZP0 - UniProtKB:Q9NYB9 - UniProtKB:Q9P2A4 review: summary: Lamellipodium (IBA) from the ABI family node PTN000048906, seeded by fly, mouse and human ABI proteins. action: ACCEPT reason: The WAVE complex, of which ABI1 is a core subunit, is recruited to the lamellipodial leading edge, and ABI1 is required for Rac-dependent lamellipodia. The zebrafish protein keeps the WAVE-binding N-terminus and coiled coil, so it is inside the clade that inherited this location; nothing argues for loss. supported_by: - reference_id: PMID:15048123 supporting_text: Consistently, inhibition of Abi1 by RNA interference (RNAi) abrogates Rac-dependent lamellipodia protrusion. - reference_id: file:DANRE/abi1a/abi1a-bioinformatics/RESULTS.md supporting_text: The N-terminal WAVE-binding region, the coiled-coil domain and the SH3 domain are conserved in both copies - term: id: GO:0030027 label: lamellipodium evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0291 review: summary: Lamellipodium from the UniProt subcellular-location mapping. action: ACCEPT reason: Same location as the IBA row, from an independent electronic source; consistent with the mammalian data on WAVE-complex relocalization to the leading edge. supported_by: - reference_id: PMID:15048123 supporting_text: The WAVE2-Abi1-Nap1-PIR121 complex is as active as the WAVE2-Abi1 sub-complex in stimulating Arp2/3, and after Rac activation it is re-localized to the leading edge of ruffles in vivo. - term: id: GO:0030175 label: filopodium evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0286 review: summary: Filopodium from the UniProt subcellular-location mapping (ARBA rule). action: KEEP_AS_NON_CORE reason: A family-level location transferred by ARBA. The cached literature places ABI1 mainly at lamellipodia and ruffles; I found no cached evidence specific to filopodia and none from zebrafish. Plausible for an adaptor of actin-based protrusions, so kept as a non-core location rather than removed. supported_by: - reference_id: PMID:15572692 supporting_text: Abi proteins localize to sites of actin polymerization in protrusive membrane structures and regulate actin dynamics in vitro. - term: id: GO:0031209 label: SCAR complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of supporting_entities: - FB:FBgn0020510 - MGI:MGI:104913 - MGI:MGI:1913860 - PANTHER:PTN000048906 - UniProtKB:Q8IZP0 - UniProtKB:Q9NYB9 - UniProtKB:Q9P2A4 - dictyBase:DDB_G0267956 review: summary: Membership of the SCAR/WAVE regulatory complex, propagated from the ABI family node (fly, mouse, human, Dictyostelium donors). action: ACCEPT reason: This is the defining function of ABI proteins. ABI1 binds the WAVE WHD domain and assembles the pentameric complex, and in the crystal structure the Abi N-terminal helices form a four-helix bundle with WAVE and HSPC300. The WAVE-binding N-terminus is 95% identical between human ABI1 and abi1a, and the coiled-coil domain is fully identical, so the zebrafish copy retains the complex-forming surface. supported_by: - reference_id: PMID:15048123 supporting_text: Abi1 interacts directly with the WHD domain of WAVE2, increases WAVE2 actin polymerization activity and mediates the assembly of a WAVE2-Abi1-Nap1-PIR121 complex. - 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 - reference_id: file:DANRE/abi1a/abi1a-bioinformatics/RESULTS.md supporting_text: The N-terminal WAVE-binding region, the coiled-coil domain and the SH3 domain are conserved in both copies - term: id: GO:0035591 label: signaling adaptor activity evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables supporting_entities: - MGI:MGI:104913 - PANTHER:PTN000048906 - UniProtKB:Q8IZP0 - UniProtKB:Q9NYB9 review: summary: Signaling adaptor activity propagated from mouse Abi1 and human ABI1/ABI2. action: ACCEPT reason: ABI1 has no enzymatic activity; it bridges upstream signalling proteins (Abl kinases via its SH3 domain, membrane receptors through the WIRS-binding surface it forms with Sra1) to the WAVE complex and Arp2/3-driven actin assembly. Signaling adaptor activity is the most informative molecular function available and matches the conserved domain architecture of abi1a. supported_by: - reference_id: PMID:7590237 supporting_text: The protein exhibits sequence similarity to homeotic genes, contains several polyproline stretches, and includes a src homology 3 (SH3) domain at its very carboxyl terminus that is required for binding to Abl proteins. - reference_id: PMID:24439376 supporting_text: Structural, biochemical, and cellular studies reveal that a sequence motif that defines these ligands binds to a highly conserved interaction surface of the WRC formed by the Sra and Abi subunits. - term: id: GO:0098858 label: actin-based cell projection evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in supporting_entities: - FB:FBgn0020510 - PANTHER:PTN000048906 - UniProtKB:Q8IZP0 - UniProtKB:Q9NYB9 review: summary: Actin-based cell projection (IBA), the parent of lamellipodium and filopodium. action: ACCEPT reason: Correct at a general level, consistent with the lamellipodium annotation; ABI proteins act at protrusive actin structures. supported_by: - reference_id: PMID:15572692 supporting_text: Abi proteins localize to sites of actin polymerization in protrusive membrane structures and regulate actin dynamics in vitro. core_functions: - description: Adaptor subunit of the WAVE regulatory (SCAR) complex that couples upstream signals to Arp2/3-dependent actin polymerization at the lamellipodial leading edge; inferred from mammalian ABI1 and the conserved WAVE-binding N-terminus and SH3 domain. Molecular function shared with abi1b. molecular_function: id: GO:0035591 label: signaling adaptor activity locations: - id: GO:0030027 label: lamellipodium in_complex: id: GO:0031209 label: SCAR complex supported_by: - reference_id: PMID:15048123 supporting_text: Thus, Abi1 orchestrates the proper assembly of the WAVE2 complex and mediates its activation at the leading edge in vivo. - reference_id: file:DANRE/abi1a/abi1a-bioinformatics/RESULTS.md supporting_text: The N-terminal WAVE-binding region, the coiled-coil domain and the SH3 domain are conserved in both copies references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees 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: PMID:7590237 title: Abl-interactor-1, a novel SH3 protein binding to the carboxy-terminal portion of the Abl protein, suppresses v-abl transforming activity. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Abstract only; original identification of mouse Abi-1 as an SH3 protein binding Abl. - id: PMID:15048123 title: Abi1 is essential for the formation and activation of a WAVE2 signalling complex. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Abstract only; establishes Abi1 as the assembly subunit of the WAVE2 complex (mammalian cells). - id: PMID:21107423 title: Structure and control of the actin regulatory WAVE complex. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: WRC crystal structure (with Abi2); defines the Abi N-terminal helices in the four-helix bundle. - id: PMID:24439376 title: The WAVE regulatory complex links diverse receptors to the actin cytoskeleton. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: WIRS-binding surface formed by Sra and Abi subunits. - id: PMID:21482783 title: Essential role for Abi1 in embryonic survival and WAVE2 complex integrity. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Mouse Abi1 knockout; embryonic lethal with heart and brain malformations; Abi2 does not compensate. - id: PMID:21173240 title: Abl-interactor-1 (Abi1) has a role in cardiovascular and placental development and is a binding partner of the alpha4 integrin. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Abstract only; independent mouse Abi1 knockout with cardiovascular and placental defects. - id: PMID:15572692 title: ABI2-deficient mice exhibit defective cell migration, aberrant dendritic spine morphogenesis, and deficits in learning and memory. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: Paralog (Abi2) evidence; the source of the neuron migration IBA. - id: PMID:32368696 title: "Systems Analysis Implicates WAVE2\_Complex in the Pathogenesis of\_Developmental Left-Sided Obstructive\_Heart\ \ Defects." findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Only zebrafish functional test of abi1a; mosaic F0 CRISPR, no heart phenotype; paralog compensation suggested but not tested. - id: file:DANRE/abi1a/abi1a-bioinformatics/RESULTS.md title: abi1a / abi1b protein, expression and synteny comparison reference_review: relevance: HIGH correctness: VERIFIED review_notes: >- Local pair analysis directly supports the ABI1 orthology call and the retained WAVE-binding, coiled-coil, and SH3 regions in both abi1 copies; its expression comparison is useful but appropriately leaves the maternal/zygotic split as a hypothesis rather than a proven ancestral partition. findings: [] suggested_questions: - question: Does the maternal/early (abi1b) versus zygotic (abi1a) temporal split reflect a partition of an ancestral ABI1 expression profile, and is gar ABI1 maternally loaded? - question: Does abi1b upregulate, or compensate, in stable abi1a mutants (PTC versus promoter-less alleles), as the CRISPR F0 study speculated? - question: Do abi1a and abi1b assemble into the same WAVE complexes (with wasf2, nckap1, cyfip1) in zebrafish tissues where both are expressed? suggested_experiments: - hypothesis: abi1a and abi1b are redundant for WAVE-complex function but partitioned in time. description: Generate stable abi1a and abi1b mutants (including maternal-zygotic abi1b) and double mutants; score gastrulation cell migration, heart looping and WAVE-complex protein stability (Wasf2, Nckap1 levels). experiment_type: genetic interaction - hypothesis: The two proteins are interchangeable. description: Rescue abi1a mutant (or double mutant) phenotypes with abi1a versus abi1b coding sequence. experiment_type: cross-rescue