Abl interactor 1 (ABI1, also known as E3B1 or Hssh3bp1) is a multidomain signaling adaptor protein and core structural subunit of the heteropentameric WAVE regulatory complex (WRC; WAVE1/2/3, ABI1/2/3, NCKAP1/NCKAP1L, CYFIP1/2, and BRK1) that couples Rac GTPase, phospholipid, and tyrosine kinase signals to Arp2/3-mediated branched actin filament nucleation at lamellipodia and filopodia tips. Its conserved N-terminal WAVE-binding (WAB) coiled-coil region assembles the WAVE:ABI:BRK1 trimer and stabilizes WRC subunits in the cytosol, whereas its central proline-rich/PxxDY region and C-terminal SH3 domain bridge non-receptor tyrosine kinases (ABL1, ABL2), Ena/VASP proteins, N-WASP, spectrin, TOCA-1, and the EPS8-ABI1-SOS1-PI3K(p85) Rac-GEF complex. ABI1 both promotes c-Abl-dependent phosphorylation of WAVE2 and ENAH/Mena via its linker-SH3 region and allosterically restrains nonmyristoylated c-Abl in trans via phospho-Tyr213 and a proximal PXXP motif, while phosphorylation at Ser88, Tyr213, and Ser216 and PTEN-dependent dephosphorylation gate WRC stability, endocytosis, macropinocytosis, and postsynaptic spine maturation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001764 neuron migration | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA annotation from Eumetazoa node PTN000825624 seeded by mouse Abi2 and C. elegans abi-1. Reason: ABI family members participate in neuronal migration via WAVE regulatory complex (WRC)-dependent actin remodeling, established genetically for mouse Abi2 (PMID:15572692) and C. elegans abi-1 (PMID:19168673). Because neuronal migration is a downstream tissue-specific developmental outcome of core WRC adaptor activity, it is retained as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000825624 · Eumetazoa ABI node SUPPORTS TRANSFER Conserved WRC role in eumetazoan neuron migration MGI:MGI:106913 · Abi2 SUPPORTS TRANSFER Abi2 KO causes neocortical and hippocampal neuron migration defects (PMID:15572692) WB:WBGene00015146 · abi-1 SUPPORTS TRANSFER abi-1 mutants show mechanosensory and motoneuron migration defects (PMID:19168673) 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:19168673 ABI-1 and UNC-53 have an overlapping expression pattern, and display similar cell migration phenotypes in the excretory cell, and in mechanosensory and motoneurons. |
| GO:0005515 protein binding | IPI PMID:11418237 Isolation of hNap1BP which interacts with human Nap1 (NCKAP1... | MODIFY | Summary: ABI1 (hNap1BP) binds the SH3/SH2 domains of the non-receptor tyrosine kinase ABL1 (UniProtKB:P00519). Reason: Bare GO:0005515 is uninformative per the protein-binding policy; ABL1 is a non-receptor tyrosine kinase bound directly by ABI1 proline-rich/pY213 and SH3/linker regions, warranting refinement to GO:0019901 (protein kinase binding). Proposed replacements: protein kinase binding Supporting Evidence: PMID:11418237 As a result of screening, we discovered a protein designated hNap1BP (human Nap1 binding protein) which is a member of the tyrosine kinase-binding protein family. In addition, hNap1BP bound to the SH3 domain of c-Abl and Nck. PMID:18328268 The mechanism, which is pertinent to the nonmyristoylated c-Abl kinase, involves high affinity concurrent binding of the phosphotyrosine pY213 to the Abl SH2 domain and binding of a proximal PXXP motif to the Abl SH3 domain. |
| GO:0005515 protein binding | IPI PMID:11418237 Isolation of hNap1BP which interacts with human Nap1 (NCKAP1... | MODIFY | Summary: ABI1 (hNap1BP) binds the SH3 domain of the adaptor protein NCK1 (UniProtKB:P16333). Reason: Bare GO:0005515 is uninformative; PMID:11418237 explicitly maps binding of ABI1/hNap1BP to the SH3 domain of Nck, supporting refinement to GO:0017124 (SH3 domain binding). Proposed replacements: SH3 domain binding Supporting Evidence: PMID:11418237 As a result of screening, we discovered a protein designated hNap1BP (human Nap1 binding protein) which is a member of the tyrosine kinase-binding protein family. In addition, hNap1BP bound to the SH3 domain of c-Abl and Nck. |
| GO:0005515 protein binding | IPI PMID:11418237 Isolation of hNap1BP which interacts with human Nap1 (NCKAP1... | REMOVE | Summary: ABI1 interacts with WRC subunit NCKAP1/NAP1 (UniProtKB:Q9Y2A7) in PMID:11418237. Reason: Bare GO:0005515 is uninformative per the protein-binding policy; association with NCKAP1 reflects stoichiometric WAVE regulatory complex assembly already captured by GO:0031209 (SCAR complex) and GO:0035591 (signaling adaptor activity). Supporting Evidence: PMID:11418237 As a result of screening, we discovered a protein designated hNap1BP (human Nap1 binding protein) which is a member of the tyrosine kinase-binding protein family. In addition, hNap1BP bound to the SH3 domain of c-Abl and Nck. |
| GO:0005515 protein binding | IPI PMID:12681507 Induction of colonic epithelial cell apoptosis by p47-depend... | MODIFY | Summary: ABI1 co-immunoprecipitates with NADPH oxidase organizer NCF1/p47phox (UniProtKB:P14598) and c-Abl. Reason: Bare GO:0005515 is uninformative; in PMID:12681507 ABI1 functions as a signaling adaptor bridging p47phox and c-Abl, warranting refinement to GO:0035591 (signaling adaptor activity). Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:12681507 p47(phox) was found to interact with the c-Abl adapter Abl interactor-1 (ABI-1), and p47(phox) coprecipitated with both ABI-1 and c-Abl. |
| GO:0005515 protein binding | IPI PMID:14565974 The eps8 family of proteins links growth factor stimulation ... | MODIFY | Summary: ABI1 interacts with EPS8L3 (UniProtKB:Q8TE67) and SOS1 in PMID:14565974. Reason: Bare GO:0005515 is uninformative; PMID:14565974 reports that EPS8L3 interacts with ABI1 and SOS1 as part of an EPS8L-ABI1-SOS1 signaling scaffold without directly mapping an SH3 domain contact on EPS8L3, supporting refinement to GO:0035591 (signaling adaptor activity) alone rather than extrapolating GO:0017124 from paralog EPS8. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:14565974 Similarly to eps8, eps8Ls interact with Abi1 and Sos-1; however, only eps8L1 and eps8L2 activate the Rac-GEF activity of Sos-1, and bind to actin in vivo. |
| GO:0005515 protein binding | IPI PMID:14565974 The eps8 family of proteins links growth factor stimulation ... | MODIFY | Summary: ABI1 interacts with EPS8L1 (UniProtKB:Q8TE68) and SOS1 to activate SOS1 Rac-GEF activity in PMID:14565974. Reason: Bare GO:0005515 is uninformative; PMID:14565974 reports that EPS8L1 interacts with ABI1 and SOS1 to activate SOS1 Rac-GEF activity without directly mapping an SH3 domain contact on EPS8L1, supporting refinement to GO:0035591 (signaling adaptor activity) alone rather than extrapolating GO:0017124 from paralog EPS8. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:14565974 Similarly to eps8, eps8Ls interact with Abi1 and Sos-1; however, only eps8L1 and eps8L2 activate the Rac-GEF activity of Sos-1, and bind to actin in vivo. |
| GO:0005515 protein binding | IPI PMID:14565974 The eps8 family of proteins links growth factor stimulation ... | MODIFY | Summary: ABI1 interacts with EPS8L2 (UniProtKB:Q9H6S3) and SOS1 to activate SOS1 Rac-GEF activity in PMID:14565974. Reason: Bare GO:0005515 is uninformative; PMID:14565974 reports that EPS8L2 interacts with ABI1 and SOS1 to activate SOS1 Rac-GEF activity without directly mapping an SH3 domain contact on EPS8L2, supporting refinement to GO:0035591 (signaling adaptor activity) alone rather than extrapolating GO:0017124 from paralog EPS8. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:14565974 Similarly to eps8, eps8Ls interact with Abi1 and Sos-1; however, only eps8L1 and eps8L2 activate the Rac-GEF activity of Sos-1, and bind to actin in vivo. |
| GO:0005515 protein binding | IPI PMID:15289329 IRSp53/Eps8 complex is important for positive regulation of ... | MODIFY | Summary: ABI1 interacts with EPS8 (UniProtKB:Q08509) in the IRSp53/EPS8/ABI1/SOS1 Rac-activating complex. Reason: Bare GO:0005515 is uninformative; ABI1 binds the EPS8 SH3 domain and scaffolds the EPS8-ABI1-SOS1 complex, supporting refinement to GO:0017124 (SH3 domain binding) and GO:0035591 (signaling adaptor activity). Proposed replacements: SH3 domain binding signaling adaptor activity Supporting Evidence: PMID:15289329 This complex synergistically activates Rac by reinforcing the formation of the Eps8/Abi-1/Sos-1 Rac-guanine nucleotide exchange factor complex, which mediates positive regulation of Rac activity. PMID:9010225 E3B1 binds to the SH3 domain of eps8 and Abl in vitro. We also demonstrated that e3B1 associates with eps8 in vivo. file:human/ABI1/ABI1-deep-research-affinage.md In parallel, ABI1 acts as the scaffold of an EPS8-ABI1-SOS1 tri-complex (SH3 domain binding SOS1, proline-rich/PxxDY region binding EPS8) that, upon recruitment of the PI3K p85 subunit and PIP3, exhibits Rac-specific GEF activity downstream of Ras to drive actin remodeling |
| GO:0005515 protein binding | IPI PMID:15289329 IRSp53/Eps8 complex is important for positive regulation of ... | MODIFY | Summary: ABI1 associates with BAIAP2/IRSp53 (UniProtKB:Q9UQB8) to reinforce EPS8/ABI1/SOS1 Rac-GEF complex assembly. Reason: Bare GO:0005515 is uninformative; this interaction reflects ABI1's scaffold/adaptor role in assembling the Rac-activating complex, warranting refinement to GO:0035591 (signaling adaptor activity). Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:15289329 This complex synergistically activates Rac by reinforcing the formation of the Eps8/Abi-1/Sos-1 Rac-guanine nucleotide exchange factor complex, which mediates positive regulation of Rac activity. |
| GO:0005515 protein binding | IPI PMID:16417406 Hem-1 complexes are essential for Rac activation, actin poly... | REMOVE | Summary: ABI1 co-purifies with hematopoietic WRC subunit NCKAP1L/Hem-1 (UniProtKB:P55160) in neutrophils. Reason: Bare GO:0005515 is uninformative per the protein-binding policy; NCKAP1L/Hem-1 association represents hematopoietic WAVE regulatory complex membership already captured by GO:0031209 (SCAR complex). Supporting Evidence: PMID:16417406 Here we characterize a family of complexes (which we term leading edge complexes), scaffolded by hematopoietic protein 1 (Hem-1), that organize the neutrophil's leading edge. |
| GO:0005515 protein binding | IPI PMID:17101133 NESH (Abi-3) is present in the Abi/WAVE complex but does not... | MODIFY | Summary: ABI1 directly binds c-Abl tyrosine kinase (ABL1, UniProtKB:P00519) and promotes WAVE2/Mena phosphorylation. Reason: Bare GO:0005515 is uninformative; ABL1 is a non-receptor protein tyrosine kinase bound by ABI1—with the C-terminal SH3 domain required for binding to Abl proteins in 99%-identical mouse ortholog Abi-1 (PMID:7590237), while chimera/domain-swap assays on the 451-aa human ABI1/AblBP4 construct in 293T cells show that human ABI1's SH3 domain alone is insufficient for c-Abl binding (and interchangeable with ABI3's SH3 domain) without its upstream central inter-domain spacer/linker region between the proline-rich regions and SH3 domain (amino acids 270–336), which is crucial for c-Abl interaction and c-Abl-mediated WAVE2 phosphorylation (PMID:26428302) alongside cellular c-Abl-mediated Mena and WAVE2 phosphorylation (PMID:17101133)—warranting refinement to GO:0019901 (protein kinase binding). Proposed replacements: protein kinase binding Supporting Evidence: PMID:7590237 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. 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:26428302 This finding showed that the SH3 domain of Abi-1 was functionally replaced by the SH3 domain of NESH/Abi-3, and that the SH3 domain of Abi-1 alone was insufficient for the binding to c-Abl. PMID:26428302 Structural studies showed that a linker region between the proline-rich regions and the Src homology 3 (SH3) domain of Abi-1 is crucial for its interaction with c-Abl and c-Abl-mediated phosphorylation of WAVE2. |
| GO:0005515 protein binding | IPI PMID:18328268 Allosteric inhibition of the nonMyristoylated c-Abl tyrosine... | MODIFY | Summary: ABI1 phosphotyrosine Tyr213 and proximal PXXP motif bind the c-Abl SH2 and SH3 domains (ABL1, UniProtKB:P00519). Reason: Bare GO:0005515 is uninformative; PMID:18328268 demonstrates concurrent binding of ABI1 pY213 and PXXP motifs to the SH2 and SH3 domains of the ABL1 kinase, supporting GO:0019901 (protein kinase binding), GO:0042169 (SH2 domain binding), and GO:0017124 (SH3 domain binding). Supporting Evidence: PMID:18328268 The mechanism, which is pertinent to the nonmyristoylated c-Abl kinase, involves high affinity concurrent binding of the phosphotyrosine pY213 to the Abl SH2 domain and binding of a proximal PXXP motif to the Abl SH3 domain. |
| GO:0005515 protein binding | IPI PMID:20598684 Abi1/Hssh3bp1 pY213 links Abl kinase signaling to p85 regula... | REMOVE | Summary: In vitro human SH2-domain library array hit between ABI1 phosphopeptide and SOCS7 (UniProtKB:O14512) in PMID:20598684. Reason: Bare GO:0005515 is uninformative per the protein-binding policy; SOCS7 (UniProtKB:O14512) was detected in an isolated SH2-domain array screen in PMID:20598684 whereas the study validated PI3K p85 as the physiological pY213 effector in cells. Supporting Evidence: PMID:20598684 Results from screening the human SH2 domain library and mapping the interaction site between Abi1 and the p85 regulatory domain of PI-3 kinase, coupled with data from cells transfected with loss-of-function p85 mutants, support the hypothesis that macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85 |
| GO:0005515 protein binding | IPI PMID:20598684 Abi1/Hssh3bp1 pY213 links Abl kinase signaling to p85 regula... | MODIFY | Summary: ABI1 interacts with ABL1 kinase (UniProtKB:P00519), which phosphorylates ABI1 Tyr213 in PMID:20598684. Reason: Bare GO:0005515 is uninformative; ABL1 is a protein tyrosine kinase that binds and phosphorylates ABI1 at Tyr213, warranting GO:0019901 (protein kinase binding). Proposed replacements: protein kinase binding Supporting Evidence: PMID:20598684 Results from screening the human SH2 domain library and mapping the interaction site between Abi1 and the p85 regulatory domain of PI-3 kinase, coupled with data from cells transfected with loss-of-function p85 mutants, support the hypothesis that macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85 PMID:18328268 The mechanism, which is pertinent to the nonmyristoylated c-Abl kinase, involves high affinity concurrent binding of the phosphotyrosine pY213 to the Abl SH2 domain and binding of a proximal PXXP motif to the Abl SH3 domain. |
| GO:0005515 protein binding | IPI PMID:20598684 Abi1/Hssh3bp1 pY213 links Abl kinase signaling to p85 regula... | REMOVE | Summary: In vitro human SH2-domain library array hit between ABI1 phosphopeptide and VAV1 (UniProtKB:P15498) in PMID:20598684. Reason: Bare GO:0005515 is uninformative per the protein-binding policy; VAV1 (UniProtKB:P15498) was detected in an isolated SH2-domain array screen in PMID:20598684 whereas the study validated PI3K p85 as the physiological pY213 effector in cells. Supporting Evidence: PMID:20598684 Results from screening the human SH2 domain library and mapping the interaction site between Abi1 and the p85 regulatory domain of PI-3 kinase, coupled with data from cells transfected with loss-of-function p85 mutants, support the hypothesis that macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85 |
| GO:0005515 protein binding | IPI PMID:20598684 Abi1/Hssh3bp1 pY213 links Abl kinase signaling to p85 regula... | REMOVE | Summary: In vitro human SH2-domain library array hit between ABI1 phosphopeptide and RASA1 (UniProtKB:P20936) in PMID:20598684. Reason: Bare GO:0005515 is uninformative per the protein-binding policy; RASA1 (UniProtKB:P20936) was detected in an isolated SH2-domain array screen in PMID:20598684 whereas the study validated PI3K p85 as the physiological pY213 effector in cells. Supporting Evidence: PMID:20598684 Results from screening the human SH2 domain library and mapping the interaction site between Abi1 and the p85 regulatory domain of PI-3 kinase, coupled with data from cells transfected with loss-of-function p85 mutants, support the hypothesis that macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85 |
| GO:0005515 protein binding | IPI PMID:20598684 Abi1/Hssh3bp1 pY213 links Abl kinase signaling to p85 regula... | MODIFY | Summary: Phosphorylated ABI1 Tyr213 binds the C-terminal SH2 domain of PI3K regulatory subunit mouse Pik3r1/p85alpha (UniProtKB:P26450). Reason: Bare GO:0005515 is uninformative; PMID:20598684 maps direct binding of ABI1 pY213 to the C-terminal SH2 domain of the PI3K regulatory subunit to regulate macropinocytosis, supporting GO:0042169 (SH2 domain binding). Proposed replacements: SH2 domain binding Supporting Evidence: PMID:20598684 Results from screening the human SH2 domain library and mapping the interaction site between Abi1 and the p85 regulatory domain of PI-3 kinase, coupled with data from cells transfected with loss-of-function p85 mutants, support the hypothesis that macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85 |
| GO:0005515 protein binding | IPI PMID:20598684 Abi1/Hssh3bp1 pY213 links Abl kinase signaling to p85 regula... | MODIFY | Summary: Phosphorylated ABI1 Tyr213 binds the C-terminal SH2 domain of PI3K regulatory subunit human PIK3R1/p85alpha (UniProtKB:P27986). Reason: Bare GO:0005515 is uninformative; PMID:20598684 maps direct binding of ABI1 pY213 to the C-terminal SH2 domain of the PI3K regulatory subunit to regulate macropinocytosis, supporting GO:0042169 (SH2 domain binding). Proposed replacements: SH2 domain binding Supporting Evidence: PMID:20598684 Results from screening the human SH2 domain library and mapping the interaction site between Abi1 and the p85 regulatory domain of PI-3 kinase, coupled with data from cells transfected with loss-of-function p85 mutants, support the hypothesis that macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85 |
| GO:0005515 protein binding | IPI PMID:20598684 Abi1/Hssh3bp1 pY213 links Abl kinase signaling to p85 regula... | MODIFY | Summary: ABI1 interacts with Abl-related tyrosine kinase ABL2/Arg (UniProtKB:P42684) in PMID:20598684. Reason: Bare GO:0005515 is uninformative; ABL2 (Arg) is a non-receptor protein tyrosine kinase of the Abl family bound by ABI1 in the human SH2-domain interaction screen (PMID:20598684, consistent with Abl-family binding first established for 99%-identical mouse ortholog Abi-1 in PMID:7590237), warranting GO:0019901 (protein kinase binding). Proposed replacements: protein kinase binding Supporting Evidence: PMID:20598684 Results from screening the human SH2 domain library and mapping the interaction site between Abi1 and the p85 regulatory domain of PI-3 kinase, coupled with data from cells transfected with loss-of-function p85 mutants, support the hypothesis that macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85 PMID:7590237 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. |
| GO:0005515 protein binding | IPI PMID:20598684 Abi1/Hssh3bp1 pY213 links Abl kinase signaling to p85 regula... | REMOVE | Summary: In vitro human SH2-domain library array hit between ABI1 phosphopeptide and VAV2 (UniProtKB:P52735) in PMID:20598684. Reason: Bare GO:0005515 is uninformative per the protein-binding policy; VAV2 (UniProtKB:P52735) was detected in an isolated SH2-domain array screen in PMID:20598684 whereas the study validated PI3K p85 as the physiological pY213 effector in cells. Supporting Evidence: PMID:20598684 Results from screening the human SH2 domain library and mapping the interaction site between Abi1 and the p85 regulatory domain of PI-3 kinase, coupled with data from cells transfected with loss-of-function p85 mutants, support the hypothesis that macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85 |
| GO:0005515 protein binding | IPI PMID:20598684 Abi1/Hssh3bp1 pY213 links Abl kinase signaling to p85 regula... | REMOVE | Summary: In vitro human SH2-domain library array hit between ABI1 phosphopeptide and CBLB (UniProtKB:Q13191) in PMID:20598684. Reason: Bare GO:0005515 is uninformative per the protein-binding policy; CBLB (UniProtKB:Q13191) was detected in an isolated SH2-domain array screen in PMID:20598684 whereas the study validated PI3K p85 as the physiological pY213 effector in cells. Supporting Evidence: PMID:20598684 Results from screening the human SH2 domain library and mapping the interaction site between Abi1 and the p85 regulatory domain of PI-3 kinase, coupled with data from cells transfected with loss-of-function p85 mutants, support the hypothesis that macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85 |
| GO:0005515 protein binding | IPI PMID:20598684 Abi1/Hssh3bp1 pY213 links Abl kinase signaling to p85 regula... | MODIFY | Summary: Phosphorylated ABI1 Tyr213 binds the C-terminal SH2 domain of PI3K regulatory subunit human PIK3R3/p55gamma (UniProtKB:Q92569). Reason: Bare GO:0005515 is uninformative; PMID:20598684 maps direct binding of ABI1 pY213 to the C-terminal SH2 domain of the PI3K regulatory subunit to regulate macropinocytosis, supporting GO:0042169 (SH2 domain binding). Proposed replacements: SH2 domain binding Supporting Evidence: PMID:20598684 Results from screening the human SH2 domain library and mapping the interaction site between Abi1 and the p85 regulatory domain of PI-3 kinase, coupled with data from cells transfected with loss-of-function p85 mutants, support the hypothesis that macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85 |
| GO:0005515 protein binding | IPI PMID:21078624 Comparison of an expanded ataxia interactome with patient me... | REMOVE | Summary: Yeast two-hybrid ataxia interactome hit with CACNA1A (UniProtKB:O00555) in PMID:21078624. Reason: Bare GO:0005515 from a high-throughput yeast two-hybrid screen (PMID:21078624) is uninformative per the protein-binding policy and lacks domain-specific or physiological validation. Supporting Evidence: PMID:21078624 We identified 118 protein interactions for CACNA1A and ATXN7 linking them to other ataxia-causing proteins and the ataxia network. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: High-throughput affinity-purification mass spectrometry co-complex detection with NCKAP1 (UniProtKB:Q9Y2A7) in HeLa GFP-AP-MS (PMID:26496610). Reason: Bare GO:0005515 from proteome-scale AP-MS co-purification is uninformative per the protein-binding policy; WRC membership is captured by GO:0031209 (SCAR complex) and specific SH3/adaptor functions are already annotated from direct biochemical studies. Supporting Evidence: PMID:26496610 Here, we have generated a library of HeLa cell lines expressing 1,125 GFP-tagged proteins under near-endogenous control, which we used as input for a next-generation interaction survey. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: High-throughput affinity-purification mass spectrometry co-complex detection with NCKAP1 (UniProtKB:Q9Y2A7) in colorectal AP-MS (PMID:31980649). Reason: Bare GO:0005515 from proteome-scale AP-MS co-purification is uninformative per the protein-binding policy; WRC membership is captured by GO:0031209 (SCAR complex) and specific SH3/adaptor functions are already annotated from direct biochemical studies. Supporting Evidence: PMID:31980649 Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput affinity-purification mass spectrometry co-complex detection with NCK1 (UniProtKB:P16333) in BioPlex AP-MS (PMID:33961781). Reason: Bare GO:0005515 from proteome-scale AP-MS co-purification is uninformative per the protein-binding policy; WRC membership is captured by GO:0031209 (SCAR complex) and specific SH3/adaptor functions are already annotated from direct biochemical studies. Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput affinity-purification mass spectrometry co-complex detection with BAIAP2 (UniProtKB:Q9UQB8) in BioPlex AP-MS (PMID:33961781). Reason: Bare GO:0005515 from proteome-scale AP-MS co-purification is uninformative per the protein-binding policy; WRC membership is captured by GO:0031209 (SCAR complex) and specific SH3/adaptor functions are already annotated from direct biochemical studies. Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput affinity-purification mass spectrometry co-complex detection with NCKAP1 (UniProtKB:Q9Y2A7) in BioPlex AP-MS (PMID:33961781). Reason: Bare GO:0005515 from proteome-scale AP-MS co-purification is uninformative per the protein-binding policy; WRC membership is captured by GO:0031209 (SCAR complex) and specific SH3/adaptor functions are already annotated from direct biochemical studies. Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: High-throughput affinity-purification mass spectrometry co-complex detection with BAIAP2 (UniProtKB:Q9UQB8) in OpenCell AP-MS (PMID:35271311). Reason: Bare GO:0005515 from proteome-scale AP-MS co-purification is uninformative per the protein-binding policy; WRC membership is captured by GO:0031209 (SCAR complex) and specific SH3/adaptor functions are already annotated from direct biochemical studies. Supporting Evidence: PMID:35271311 We combined genome engineering, confocal live-cell imaging, mass spectrometry, and data science to systematically map the localization and interactions of human proteins. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: High-throughput affinity-purification mass spectrometry co-complex detection with NCKAP1 (UniProtKB:Q9Y2A7) in OpenCell AP-MS (PMID:35271311). Reason: Bare GO:0005515 from proteome-scale AP-MS co-purification is uninformative per the protein-binding policy; WRC membership is captured by GO:0031209 (SCAR complex) and specific SH3/adaptor functions are already annotated from direct biochemical studies. Supporting Evidence: PMID:35271311 We combined genome engineering, confocal live-cell imaging, mass spectrometry, and data science to systematically map the localization and interactions of human proteins. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: High-throughput affinity-purification mass spectrometry co-complex detection with NCK1 (UniProtKB:P16333) in U2OS AP-MS (PMID:40205054). Reason: Bare GO:0005515 from proteome-scale AP-MS co-purification is uninformative per the protein-binding policy; WRC membership is captured by GO:0031209 (SCAR complex) and specific SH3/adaptor functions are already annotated from direct biochemical studies. Supporting Evidence: PMID:40205054 Here we construct a global map of human subcellular architecture through joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins in U2OS osteosarcoma cells. |
| GO:0005515 protein binding | IPI PMID:9010225 Isolation and characterization of e3B1, an eps8 binding prot... | MODIFY | Summary: ABI1 (E3B1) binds the SH3 domain of EPS8 (UniProtKB:Q08509) in vitro and associates with EPS8 in vivo. Reason: Bare GO:0005515 is uninformative; PMID:9010225 directly demonstrates binding of E3B1/ABI1 to the SH3 domain of EPS8, warranting refinement to GO:0017124 (SH3 domain binding). Proposed replacements: SH3 domain binding Supporting Evidence: PMID:9010225 E3B1 binds to the SH3 domain of eps8 and Abl in vitro. We also demonstrated that e3B1 associates with eps8 in vivo. |
| GO:0005515 protein binding | IPI PMID:9593709 Identification of a candidate human spectrin Src homology 3 ... | MODIFY | Summary: ABI1 (Hssh3bp1) binds the Abl SH3 domain of ABL1 tyrosine kinase (UniProtKB:P00519) in PMID:9593709. Reason: Bare GO:0005515 is uninformative; PMID:9593709 maps a dedicated Abl-SH3 binding region in ABI1 that binds the ABL1 kinase, supporting GO:0019901 (protein kinase binding) and GO:0017124 (SH3 domain binding). Proposed replacements: protein kinase binding SH3 domain binding Supporting Evidence: PMID:9593709 Mapping of SH3 binding regions revealed the presence of two alphaI SH3 domain binding regions and one Abl-SH3 domain binding region. |
| GO:0005515 protein binding | IPI PMID:9593709 Identification of a candidate human spectrin Src homology 3 ... | MODIFY | Summary: ABI1 (Hssh3bp1) binds the SH3 domain of erythroid alpha-I spectrin SPTA1 (UniProtKB:P02549) via two SH3-binding regions. Reason: Bare GO:0005515 is uninformative; PMID:9593709 maps two alpha-I spectrin SH3 domain-binding regions in ABI1, warranting refinement to GO:0030507 (spectrin binding) and GO:0017124 (SH3 domain binding). Proposed replacements: spectrin binding SH3 domain binding Supporting Evidence: PMID:9593709 Mapping of SH3 binding regions revealed the presence of two alphaI SH3 domain binding regions and one Abl-SH3 domain binding region. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping for nuclear localization of ABI1. Reason: ABI1 undergoes leptomycin B-sensitive nucleocytoplasmic shuttling (PMID:15143189) and Abl-dependent nuclear translocation following synaptic NMDA stimulation (PMID:17304222), making nuclear localization real but secondary to its cytoplasmic/leading-edge WRC function. Supporting Evidence: PMID:15143189 Further, we demonstrated that Abi-1 shuttles in and out of the nucleus in a leptomycin B (LMB)-dependent manner and that complete nuclear translocation of Abi-1 in the absence of LMB requires the combined inactivation of the SNARE, WAB, and SH3 domains of Abi-1. PMID:17304222 Abi-1 translocates upon NMDA application from PSDs to nuclei. Nuclear entry depends on abelson kinase activity. Abi-1 co-immunoprecipitates with the transcription factor complex of Myc/Max proteins and enhances E-box-regulated gene transcription. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | MODIFY | Summary: UniProt subcellular-location mapping to the cytoplasm, refined to the more specific accepted term GO:0005829 (cytosol). Reason: GO:0005737 (cytoplasm) is not one of the five root organelle terms and is broader than warranted because the more specific descendant GO:0005829 (cytosol) is directly supported for cytosolic e3B1/ABI1 (PMID:9010225) and already ACCEPTED on human ABI1. Proposed replacements: cytosol Supporting Evidence: PMID:9010225 We show that anti-e3B1 antibodies detect three cytosolic protein species of 65, 68 and 72 kDa in cell lysate isolated from asynchronously growing NIH3T3 cells. |
| GO:0005783 endoplasmic reticulum | TAS PMID:9593709 Identification of a candidate human spectrin Src homology 3 ... | MARK AS OVER ANNOTATED | Summary: TAS annotation to endoplasmic reticulum from overexpressed GFP-Hssh3bp1 puncta in NIH3T3 cells (PMID:9593709). Reason: Per organelle curation policy, GO:0005783 is not supported as a native residence for ABI1: PMID:9593709 only observed cytoplasmic punctate fluorescence of an overexpressed GFP fusion that resembled a reticulovesicular pattern without ER marker co-localization, whereas endogenous ABI1 is a soluble cytosolic/cortical actin-regulatory scaffold. Supporting Evidence: PMID:9593709 Overexpression of the green fluorescent protein fusion of the SH3 domain-binding protein in NIH3T3 cells resulted in cytoplasmic punctate fluorescence characteristic of the reticulovesicular system. |
| GO:0005829 cytosol | TAS PMID:9010225 Isolation and characterization of e3B1, an eps8 binding prot... | ACCEPT | Summary: Cytosolic localization of ABI1 (E3B1) demonstrated by biochemical fractionation in PMID:9010225. Reason: Anti-E3B1/ABI1 antibodies detect cytosolic 65, 68, and 72 kDa species in cell lysates, and the basal WRC resides in the cytosol prior to Rac1/PIP3-mediated membrane recruitment. Supporting Evidence: PMID:9010225 We show that anti-e3B1 antibodies detect three cytosolic protein species of 65, 68 and 72 kDa in cell lysate isolated from asynchronously growing NIH3T3 cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2029465 | ACCEPT | Summary: Cytosolic localization of ABI1 as part of the WAVE regulatory complex in Reactome WRC activation reaction R-HSA-2029465. Reason: ABI1 is a core subunit of the cytosolic WAVE regulatory complex that is recruited to the plasma membrane cytosolic face upon GTP-Rac and kinase activation. Supporting Evidence: Reactome:R-HSA-2029465 The WRC consists of a WAVE family protein (WASF1, WASF2 or WASF3 - commonly known as WAVE1, WAVE2 or WAVE3), ABI (Abelson-interacting protein), NCKAP1 (NAP1, p125NAP1), CYFIP1 (SRA1) or the closely related CYFIP2 (PIR121), and BRK1 (HSPC300, BRICK). PMID:9010225 We show that anti-e3B1 antibodies detect three cytosolic protein species of 65, 68 and 72 kDa in cell lysate isolated from asynchronously growing NIH3T3 cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2029466 | ACCEPT | Summary: Cytosolic localization of ABI1 as part of the WAVE regulatory complex in Reactome Arp2/3 F-actin nucleation reaction R-HSA-2029466. Reason: ABI1 is a core subunit of the cytosolic WAVE regulatory complex that is recruited to the plasma membrane cytosolic face upon GTP-Rac and kinase activation. Supporting Evidence: Reactome:R-HSA-2029466 Once activated, the ARP2/3 complex nucleates new actin filaments that extend from the sides of pre-existing mother actin filaments at a 70-degree angle to form Y-branched networks (Firat-Karalar & Welch 2010). PMID:9010225 We show that anti-e3B1 antibodies detect three cytosolic protein species of 65, 68 and 72 kDa in cell lysate isolated from asynchronously growing NIH3T3 cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2029469 | ACCEPT | Summary: Cytosolic localization of ABI1 as part of the WAVE regulatory complex in Reactome ERK phosphorylation of WAVE2 and ABI1 R-HSA-2029469. Reason: ABI1 is a core subunit of the cytosolic WAVE regulatory complex that is recruited to the plasma membrane cytosolic face upon GTP-Rac and kinase activation. Supporting Evidence: Reactome:R-HSA-2029469 Active ERK (Mitogen activated protein kinase 3) phosphorylates the WAVE regulatory complex (WRC) on multiple serine/threonine sites within the proline-rich domains (PRDs) of WAVE2 and ABI1. PMID:9010225 We show that anti-e3B1 antibodies detect three cytosolic protein species of 65, 68 and 72 kDa in cell lysate isolated from asynchronously growing NIH3T3 cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2130194 | ACCEPT | Summary: Cytosolic localization of ABI1 as part of the WAVE regulatory complex in Reactome ABL phosphorylation of WAVE complex R-HSA-2130194. Reason: ABI1 is a core subunit of the cytosolic WAVE regulatory complex that is recruited to the plasma membrane cytosolic face upon GTP-Rac and kinase activation. Supporting Evidence: Reactome:R-HSA-2130194 Abelson interactor-1 (ABL) tyrosine kinase phosphorylates the strictly conserved tyrosine 150 in WAVE2 (Y151 in WAVE1 and WAVE3) (Leng et al. 2003, Chen et al. 2010). PMID:9010225 We show that anti-e3B1 antibodies detect three cytosolic protein species of 65, 68 and 72 kDa in cell lysate isolated from asynchronously growing NIH3T3 cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2197690 | ACCEPT | Summary: Cytosolic localization of ABI1 as part of the WAVE regulatory complex in Reactome detachment of WASP/WAVE from actin branch R-HSA-2197690. Reason: ABI1 is a core subunit of the cytosolic WAVE regulatory complex that is recruited to the plasma membrane cytosolic face upon GTP-Rac and kinase activation. Supporting Evidence: Reactome:R-HSA-2197690 After incorporation at the branch, the actin bound to VCA domain of WASP/WAVE undergoes ATP hydrolysis and this destabilizes its interaction with WASP/WAVE. PMID:9010225 We show that anti-e3B1 antibodies detect three cytosolic protein species of 65, 68 and 72 kDa in cell lysate isolated from asynchronously growing NIH3T3 cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013145 | ACCEPT | Summary: Cytosolic localization of ABI1 as part of the WAVE regulatory complex in Reactome RAC1 effector binding reaction R-HSA-9013145. Reason: ABI1 is a core subunit of the cytosolic WAVE regulatory complex that is recruited to the plasma membrane cytosolic face upon GTP-Rac and kinase activation. Supporting Evidence: Reactome:R-HSA-9013145 In its GTP bound active form, plasma membrane associated RAC1 binds to the following cytosolic and plasma membrane effectors: PMID:9010225 We show that anti-e3B1 antibodies detect three cytosolic protein species of 65, 68 and 72 kDa in cell lysate isolated from asynchronously growing NIH3T3 cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9018808 | ACCEPT | Summary: Cytosolic localization of ABI1 as part of the WAVE regulatory complex in Reactome RAC3 effector binding reaction R-HSA-9018808. Reason: ABI1 is a core subunit of the cytosolic WAVE regulatory complex that is recruited to the plasma membrane cytosolic face upon GTP-Rac and kinase activation. Supporting Evidence: Reactome:R-HSA-9018808 In its active form, plasma membrane associated RAC3 binds to the following effectors: PMID:9010225 We show that anti-e3B1 antibodies detect three cytosolic protein species of 65, 68 and 72 kDa in cell lysate isolated from asynchronously growing NIH3T3 cells. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to the cytoskeleton, accepted at the broad organelle/network level for a dynamically recruited cytoskeletal regulatory adaptor. Reason: Broad GO:0005856 is deliberately accepted as-is because ABI1 is a cytosolic signaling adaptor and WAVE regulatory complex subunit dynamically recruited across multiple cytoskeletal remodeling and cortical spectrin-scaffolded sites rather than an intrinsic structural subunit of a single filament polymer (PMID:9593709, PMID:15048123). Supporting Evidence: PMID:9593709 Mapping of SH3 binding regions revealed the presence of two alphaI SH3 domain binding regions and one Abl-SH3 domain binding region. PMID:15048123 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. |
| GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway | TAS PMID:9010225 Isolation and characterization of e3B1, an eps8 binding prot... | MODIFY | Summary: TAS annotation from PMID:9010225 describing EGF-induced hyperphosphorylation of E3B1/ABI1 and EPS8 complex formation. Reason: GO:0007169 is broader than warranted by PMID:9010225, which specifically characterizes E3B1/ABI1 phosphorylation and EPS8-SOS1 signaling downstream of epidermal growth factor receptor (EGFR) stimulation; refine to GO:0007173. Proposed replacements: epidermal growth factor receptor signaling pathway Supporting Evidence: PMID:9010225 Time course studies initiated by the addition of epidermal growth factor (EGF) revealed that the p72e3B1 started to accumulate at 4 h, peaked at 8 h and remained high until 24 h. PMID:10499589 We also show that Eps8, E3b1 and Sos-1 form a tri-complex in vivo that exhibits Rac-specific GEF activity in vitro. |
| GO:0008092 cytoskeletal protein binding | TAS PMID:9593709 Identification of a candidate human spectrin Src homology 3 ... | MODIFY | Summary: TAS annotation from PMID:9593709 for binding of Hssh3bp1/ABI1 to erythroid alpha-I spectrin. Reason: GO:0008092 (cytoskeletal protein binding) is more general than the specific alpha-I spectrin SH3 interaction demonstrated in PMID:9593709; refine to GO:0030507 (spectrin binding). Proposed replacements: spectrin binding Supporting Evidence: PMID:9593709 Mapping of SH3 binding regions revealed the presence of two alphaI SH3 domain binding regions and one Abl-SH3 domain binding region. |
| GO:0008154 actin polymerization or depolymerization | NAS PMID:11516653 The Abl interactor proteins localize to sites of actin polym... | MODIFY | Summary: NAS annotation from PMID:11516653 based on recruitment of EYFP-ABI1 to sites of actin polymerization at lamellipodia and filopodia tips. Reason: ABI1 does not directly polymerize or depolymerize actin filaments; as an essential subunit of the WAVE regulatory complex, it positively regulates WAVE- and Arp2/3-mediated branched actin nucleation (harmonized with ABI2). Proposed replacements: positive regulation of Arp2/3 complex-mediated actin nucleation 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. PMID:15048123 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. |
| GO:0008285 negative regulation of cell population proliferation | TAS PMID:9010225 Isolation and characterization of e3B1, an eps8 binding prot... | MARK AS OVER ANNOTATED | Summary: TAS annotation from PMID:9010225 based on slower growth of NIH/EGFR fibroblasts ectopically overexpressing E3B1/ABI1. Reason: Reduced growth upon ectopic overexpression in NIH/EGFR fibroblasts reflects sequestration of mitogenic SH3/Ras-Rac adaptors rather than an evolved antiproliferative core function; genetic loss of Abi1 instead causes embryonic lethality at E11.5 (PMID:21482783). Supporting Evidence: PMID:9010225 Finally, we demonstrate that NIH/EGFR fibroblasts overexpressing e3B1 grow more slowly relative to matched controls. PMID:21482783 The essential function of Abi1 in WAVE complexes and their regulation might explain the observed embryonic lethality of Abi1-deficient embryos, which survived until approximately embryonic day 11.5 and displayed malformations in the developing heart and brain. |
| GO:0014069 postsynaptic density | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping to the postsynaptic density. Reason: Supported by direct biochemical and super-resolution imaging in mammalian neurons showing ABI1 enrichment in dendritic spine postsynaptic densities with Shank3 and the WRC (PMID:17304222, PMID:25293574); retained as a specialized neuronal localization. Supporting Evidence: PMID:17304222 During early neuronal development, Abi-1 is localized in neurites and growth cones; at later stages, the protein is enriched in dendritic spines and PSDs, as are components of a trimeric complex consisting of Abi-1, Eps8 and Sos-1. PMID:25293574 The PSD is a persistent confinement zone for IRSp53 and the WAVE complex, an activator of the Arp2/3 complex. |
| GO:0017124 SH3 domain binding | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA electronic annotation for SH3 domain binding. Reason: ABI1 contains C-terminal polyproline and PxxDY motifs that directly bind the SH3 domains of c-Abl, EPS8, NCK1, spectrin, and TOCA-1 (PMID:9010225, PMID:18328268, PMID:19798448). Supporting Evidence: PMID:9010225 E3B1 binds to the SH3 domain of eps8 and Abl in vitro. We also demonstrated that e3B1 associates with eps8 in vivo. PMID:18328268 The mechanism, which is pertinent to the nonmyristoylated c-Abl kinase, involves high affinity concurrent binding of the phosphotyrosine pY213 to the Abl SH2 domain and binding of a proximal PXXP motif to the Abl SH3 domain. PMID:19798448 To this end, we utilized the SH3 domain of TOCA-1 to search for novel interactors, employing phage display libraries of human polypeptides [47]. We found ABI-1 among the most represented interactors (not shown). We validated this interaction by showing that endogenous and ectopically expressed TOCA-1 and ABI-1 coimmunoprecipitated (Figure 7A and 7B), and interacted in in vitro binding experiments using immobilized SH3 domain of TOCA-1 (Figure S7C). |
| GO:0017124 SH3 domain binding | IPI PMID:19798448 Requirements for F-BAR proteins TOCA-1 and TOCA-2 in actin d... | ACCEPT | Summary: IPI annotation from PMID:19798448 showing ABI1 binding to the SH3 domain of F-BAR protein FNBP1L/TOCA-1 (UniProtKB:Q5T0N5). Reason: Direct biochemical evidence in PMID:19798448 demonstrates that human ABI1 directly binds the immobilized SH3 domain of TOCA-1 and bridges WAVE2 to TOCA-1. Supporting Evidence: PMID:19798448 To this end, we utilized the SH3 domain of TOCA-1 to search for novel interactors, employing phage display libraries of human polypeptides [47]. We found ABI-1 among the most represented interactors (not shown). We validated this interaction by showing that endogenous and ectopically expressed TOCA-1 and ABI-1 coimmunoprecipitated (Figure 7A and 7B), and interacted in in vitro binding experiments using immobilized SH3 domain of TOCA-1 (Figure S7C). |
| GO:0030027 lamellipodium | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation from ancestral node PTN000048906 for active localization at the lamellipodium. Reason: Directly supported on human ABI1 itself (a PAINT seed) by live-cell imaging and biochemical WRC reconstitution (PMID:11516653, PMID:15048123, PMID:17101133). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000048906 · Ancestral ABI family node SUPPORTS TRANSFER Seeded directly by human ABI1, ABI2, ABI3, mouse Abi1/Abi2, and Drosophila Abi UniProtKB:Q8IZP0 · ABI1 SUPPORTS TRANSFER Self-seed with IDA evidence at lamellipodia tips (PMID:11516653) 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. PMID:15048123 Consistently, inhibition of Abi1 by RNA interference (RNAi) abrogates Rac-dependent lamellipodia protrusion. |
| GO:0030027 lamellipodium | IDA PMID:11516653 The Abl interactor proteins localize to sites of actin polym... | ACCEPT | Summary: IDA annotation from PMID:11516653 showing EYFP-ABI1 recruitment to the tips of protruding lamellipodia. Reason: Landmark live-cell microscopy study demonstrating ABI1 localization precisely at the leading edge of lamellipodia during active actin polymerization. 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 | IDA PMID:17101133 NESH (Abi-3) is present in the Abi/WAVE complex but does not... | ACCEPT | Summary: IDA annotation from PMID:17101133 (abstract-only in local cache) for ABI1 localization at lamellipodia, corroborated by direct live-cell microscopy in PMID:11516653. Reason: PMID:17101133 is abstract-only in our local publication cache and its abstract summarizes Abi-1/Abi-2/Abi-3 WAVE complex co-immunoprecipitation and c-Abl phosphorylation rather than fluorescence microscopy, so we defer to the curator's full-text IDA reading while citing PMID:11516653 for direct verbatim lamellipodia-tip recruitment evidence. 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. 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:0000120 | ACCEPT | Summary: Combined IEA annotation for lamellipodium localization. Reason: Consistent with direct live-cell EYFP-Abi1 recruitment at lamellipodia tips (PMID:11516653) and the curator-deferred IDA annotation on human ABI1 (PMID:17101133, abstract-only locally). 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: UniProt subcellular-location mapping to the filopodium. Reason: Supported by direct live-cell imaging in PMID:11516653 showing ABI1 recruitment to filopodial 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:0030296 protein tyrosine kinase activator activity | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara IEA orthology transfer from mouse Abi1 (UniProtKB:Q8CBW3) for c-Abl protein tyrosine kinase activator activity. Reason: Ensembl Compara orthology transfer (GO_REF:0000107) from 99%-identical 1:1 mouse ortholog Abi1 (UniProtKB:Q8CBW3), where MGI curates GO:0030296 (IDA) from PMID:12672821. In mouse Abi-1, the C-terminal SH3 domain is required for binding to Abl proteins (PMID:7590237), while chimera/domain-swap assays on the 451-aa human ABI1/AblBP4 construct in 293T cells show that human ABI1's SH3 domain alone is insufficient for c-Abl binding without its upstream central inter-domain spacer/linker region between the proline-rich regions and SH3 domain (amino acids 270–336; PMID:26428302), enabling ABI1 to promote c-Abl-mediated tyrosine phosphorylation of Mena and WAVE2 (PMID:12672821, PMID:17101133, PMID:26428302), matching the PTHR10460 family review (abl_pndy_py213_s216 contributing to GO:0061098 and SUBFAMILY_ONLY scope across ABI1, ABI2, and metazoan SF0, in contrast to vertebrate ABI3/Abi3's loss of c-Abl co-activation in PMID:17101133), whereas coexpressed full-length wild-type human ABI1 (unlike the Y213F mutant) can also mediate Y213-dependent allosteric inhibition of nonmyristoylated c-Abl pY412 phosphorylation and pervanadate-induced kinase activity in human LNCaP cells via concurrent pY213-SH2 and PXXP-SH3 engagement in trans (PMID:18328268). Although Mena-selective enhancement over c-Cbl in PMID:12672821 ('promoted c-Abl-mediated tyrosine phosphorylation of Mena but not other substrates such as c-Cbl') is also compatible with adaptor-mediated substrate presentation (GO:0035591, the reading adopted for GO:0061098 KEEP_AS_NON_CORE in mouse Abi2), ACCEPT is retained here by curator deference to the donor mouse IDA annotation (PMID:12672821, abstract-only locally) alongside human ABI1's own abstract-only IDA annotation on GO:0061098 (PMID:17101133), noting mouse Abi2 for future family-level harmonization. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8CBW3 · Abi1 SUPPORTS TRANSFER 1:1 mammalian ortholog shown in PMID:12672821 and PMID:17101133 to promote c-Abl substrate phosphorylation Supporting Evidence: PMID:7590237 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. PMID:12672821 Importantly, Abi-1 dramatically promoted c-Abl-mediated tyrosine phosphorylation of Mena but not other substrates such as c-Cbl. 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:26428302 This finding showed that the SH3 domain of Abi-1 was functionally replaced by the SH3 domain of NESH/Abi-3, and that the SH3 domain of Abi-1 alone was insufficient for the binding to c-Abl. PMID:26428302 Structural studies showed that a linker region between the proline-rich regions and the Src homology 3 (SH3) domain of Abi-1 is crucial for its interaction with c-Abl and c-Abl-mediated phosphorylation of WAVE2. |
| GO:0030296 protein tyrosine kinase activator activity | ISS GO_REF:0000024 | ACCEPT | Summary: Curated ARUK-UCL ISS sequence-similarity transfer from mouse Abi1 (UniProtKB:Q8CBW3) for c-Abl protein tyrosine kinase activator activity. Reason: Curated sequence-similarity transfer (GO_REF:0000024) from 99%-identical mouse ortholog Abi1 (UniProtKB:Q8CBW3, MGI IDA on PMID:12672821) reinforcing the Ensembl Compara IEA row on GO:0030296 and human ABI1's direct GO:0061098 IDA counterpart (PMID:17101133). Whereas 99%-identical mouse Abi-1 requires its C-terminal SH3 domain for binding to Abl proteins (PMID:7590237), chimera/domain-swap assays on the 451-aa human ABI1/AblBP4 construct in 293T cells show that human ABI1's SH3 domain alone is insufficient for c-Abl binding without its upstream central inter-domain spacer/linker region between the proline-rich regions and SH3 domain (amino acids 270–336; PMID:26428302; PTHR10460#abl_pndy_py213_s216, SUBFAMILY_ONLY across ABI1/ABI2/metazoan SF0 and absent in ABI3/Abi3); together these conserved determinants enable ABI1 to promote cellular c-Abl-mediated phosphorylation of Mena and WAVE2 (PMID:12672821, PMID:17101133, PMID:26428302), while coexpressed full-length wild-type human ABI1 (unlike Y213F) can conversely inhibit nonmyristoylated c-Abl pY412 phosphorylation and pervanadate-stimulated kinase activity in human LNCaP cells via pY213-SH2/PXXP-SH3 engagement in trans (PMID:18328268). Despite the Mena-versus-c-Cbl substrate selectivity reported in PMID:12672821 being alternatively interpretable as GO:0035591 substrate scaffolding (as curated for GO:0061098 KEEP_AS_NON_CORE in mouse Abi2), ACCEPT is maintained in deference to the underlying abstract-only IDA curations on donor mouse Abi1 (PMID:12672821) and human ABI1 (PMID:17101133), with mouse Abi2 noted for future family-level harmonization. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8CBW3 · Abi1 SUPPORTS TRANSFER 1:1 mammalian ortholog shown in PMID:12672821 and PMID:17101133 to promote c-Abl substrate phosphorylation Supporting Evidence: PMID:7590237 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. PMID:12672821 Importantly, Abi-1 dramatically promoted c-Abl-mediated tyrosine phosphorylation of Mena but not other substrates such as c-Cbl. 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:26428302 This finding showed that the SH3 domain of Abi-1 was functionally replaced by the SH3 domain of NESH/Abi-3, and that the SH3 domain of Abi-1 alone was insufficient for the binding to c-Abl. PMID:26428302 Structural studies showed that a linker region between the proline-rich regions and the Src homology 3 (SH3) domain of Abi-1 is crucial for its interaction with c-Abl and c-Abl-mediated phosphorylation of WAVE2. |
| GO:0030426 growth cone | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping to the neuronal growth cone. Reason: Supported by biochemical fractionation of growth cone particles and neuronal immunolocalization (PMID:10995551, PMID:17304222); kept as a non-core neuronal compartment. Supporting Evidence: PMID:10995551 Both Abi and Abl proteins are present in synaptosomes and growth cone particles. PMID:17304222 During early neuronal development, Abi-1 is localized in neurites and growth cones; at later stages, the protein is enriched in dendritic spines and PSDs, as are components of a trimeric complex consisting of Abi-1, Eps8 and Sos-1. |
| GO:0031209 SCAR complex | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation from PTN000048906 for membership in the heteropentameric SCAR/WAVE regulatory complex. Reason: Defining conserved core complex of the ABI family across Metazoa, Dictyostelium, and plants, directly seeded by human ABI1-WAVE2 complex assembly (PMID:15048123) and structurally defined by the heteropentameric WRC crystal structure (WAVE1:Abi2:HSPC300; PMID:21107423). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000048906 · Ancestral ABI family node SUPPORTS TRANSFER Conserved WRC/SCAR subunit across eukaryotes UniProtKB:Q8IZP0 · ABI1 SUPPORTS TRANSFER Direct IDA evidence for WRC incorporation (PMID:15048123, PMID:26428302) and conserved WRC heteropentamer crystal structure (PMID:21107423) Supporting Evidence: PMID:15048123 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. PMID:21107423 MiniWRC can be delineated into two subcomplexes: an Sra1:Nap1 dimer and a WAVE1:Abi2:HSPC300 trimer |
| GO:0031209 SCAR complex | IDA PMID:21107423 Structure and control of the actin regulatory WAVE complex. | ACCEPT | Summary: IDA annotation from the crystal structure and biochemical reconstitution of the human WAVE regulatory complex (PMID:21107423). Reason: Definitive structural and biochemical demonstration in PMID:21107423 (crystallized as the WAVE1:Abi2:HSPC300 trimer subcomplex paired with Sra1:Nap1 and validated by HeLa WAVE2 WRC co-immunoprecipitation) defining the conserved Abi subunit position in the heteropentameric WRC. Supporting Evidence: PMID:21107423 MiniWRC can be delineated into two subcomplexes: an Sra1:Nap1 dimer and a WAVE1:Abi2:HSPC300 trimer |
| GO:0031209 SCAR complex | IDA PMID:26428302 The NESH/Abi-3-based WAVE2 complex is functionally distinct ... | ACCEPT | Summary: IDA annotation from PMID:26428302 demonstrating endogenous ABI1-based WAVE2 complex assembly. Reason: Direct co-immunoprecipitation of endogenous human ABI1 (Abi-1) with WAVE2 and PIR121/Sra1 in human HUVEC lysates (alongside tagged ABI1 self-association in human 293T cells and competitive displacement of endogenous mouse Abi-1 upon ectopic NESH/Abi-3 expression in mouse NIH3T3 fibroblasts) in PMID:26428302, reinforcing direct ABI1-WHD binding and WAVE2-Abi1-Nap1-PIR121 complex assembly (PMID:15048123). Supporting Evidence: PMID:26428302 In the HUVEC cells, both Abi-1 and NESH/Abi-3 co-precipitated WAVE2 and PIR121/Sra1 (lanes 7 and 10). PMID:26428302 The expression of NESH/Abi-3 caused degradation of endogenous Abi-1, which led to the formation of a NESH/Abi-3-based WAVE2 complex PMID:15048123 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. |
| GO:0031209 SCAR complex | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA annotation for SCAR/WAVE complex membership. Reason: Reinforces direct ABI1-WAVE2 complex assembly (PMID:15048123) and the conserved heteropentameric WRC crystal structure (WAVE1:Abi2:HSPC300; PMID:21107423) for ABI1's core complex. Supporting Evidence: PMID:15048123 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. PMID:21107423 MiniWRC can be delineated into two subcomplexes: an Sra1:Nap1 dimer and a WAVE1:Abi2:HSPC300 trimer |
| GO:0031252 cell leading edge | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara IEA orthology transfer from mouse Abi1 (UniProtKB:Q8CBW3) for cell leading edge localization. Reason: Ensembl Compara orthology transfer (GO_REF:0000107) from donor mouse Abi1 (UniProtKB:Q8CBW3), where live-cell TIRF imaging tracks Abi1-YFP at the tips of protruding lamellipodia at the leading edge of migrating murine B16F10 cells (PMID:19200726), reinforced by EYFP-ABI1 recruitment to lamellipodia and filopodia tips (PMID:11516653) and leading-edge Hem-1/WAVE complexes in human leukocytes (PMID:16417406). Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8CBW3 · Abi1 SUPPORTS TRANSFER Live-cell TIRF imaging tracks mouse Abi1-YFP at protruding lamellipodia tips at the leading edge of murine B16F10 cells (PMID:19200726; corroborated by PMID:16831833) 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. PMID:16417406 Here we characterize a family of complexes (which we term leading edge complexes), scaffolded by hematopoietic protein 1 (Hem-1), that organize the neutrophil's leading edge. PMID:19200726 the WAVE complex localizes to the tips of protruding lamellipodia in B16F10 murine melanoma cells [13] (Fig. 1A, Movie S1); and this leading edge localization represents rapidly cycling WAVE complex (half life 8.6 s for WAVE in murine melanoma cells compared to 6.4 s for the Hem-1 component of the neutrophil WAVE complex [6, 14]). To determine whether actin assembly is required for WAVE complex recycling in cells other than neutrophils, we depolymerized the actin cytoskeleton in B16F10 cells expressing a fluorescently tagged subunit of the WAVE complex (Abi1). |
| GO:0032433 filopodium tip | IDA PMID:11516653 The Abl interactor proteins localize to sites of actin polym... | ACCEPT | Summary: IDA annotation from PMID:11516653 demonstrating EYFP-ABI1 enrichment at filopodium tips. Reason: Direct live-cell imaging evidence showing recruitment of ABI1 to sites of actin assembly at 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:0032433 filopodium tip | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA electronic annotation for filopodium tip localization. Reason: Supported by direct experimental IDA evidence in PMID:11516653. 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: IBA annotation from PTN000048906 for signaling adaptor activity. Reason: Core conserved molecular function of ABI1 bridging WAVE/NAP1/CYFIP/BRK1, EPS8/SOS1/PI3K-p85, and c-Abl to actin-nucleating machinery. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000048906 · Ancestral ABI family node SUPPORTS TRANSFER Seeded directly by human ABI1, ABI2, and mouse Abi1 UniProtKB:Q8IZP0 · ABI1 SUPPORTS TRANSFER Direct experimental IDA support (PMID:17101133) Supporting Evidence: PMID:10499589 We also show that Eps8, E3b1 and Sos-1 form a tri-complex in vivo that exhibits Rac-specific GEF activity in vitro. PMID:15048123 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. 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:0035591 signaling adaptor activity | IDA PMID:17101133 NESH (Abi-3) is present in the Abi/WAVE complex but does not... | ACCEPT | Summary: IDA annotation from PMID:17101133 demonstrating ABI1 adaptor function bridging c-Abl to WAVE2 and Mena in the WAVE complex. Reason: Core molecular function of ABI1. 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: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:0035591 signaling adaptor activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA annotation for signaling adaptor activity. Reason: Consistent with direct IDA evidence on human ABI1. Supporting Evidence: PMID:15048123 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. 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:0035591 signaling adaptor activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS orthology annotation from mouse Abi1 (UniProtKB:Q8CBW3) for signaling adaptor activity. Reason: Curated sequence-similarity transfer (ISS, GO_REF:0000024) from mouse Abi1 reinforcing direct human IDA evidence (PMID:15048123, PMID:17101133) and mouse Abi1 IDA evidence (PMID:12672821). Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8CBW3 · Abi1 SUPPORTS TRANSFER Mouse Abi1 bridges c-Abl to Mena and WAVE2 (PMID:12672821) Supporting Evidence: PMID:12672821 Importantly, Abi-1 dramatically promoted c-Abl-mediated tyrosine phosphorylation of Mena but not other substrates such as c-Cbl. PMID:15048123 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. 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:0043005 neuron projection | IEA GO_REF:0000107 | MODIFY | Summary: IEA orthology transfer from mouse Abi1 (UniProtKB:Q8CBW3) for neuron projection localization, refined to growth cone and dendritic spine. Reason: GO:0043005 (neuron projection) is not a root organelle term and is broader than warranted because PMID:17304222 directly demonstrates localization to the more specific neuron projection descendants GO:0030426 (growth cone, already present as an existing row in this review) and GO:0043197 (dendritic spine), alongside postsynaptic densities (GO:0014069, already carried in this review under postsynapse). Proposed replacements: growth cone dendritic spine Supporting Evidence: PMID:17304222 During early neuronal development, Abi-1 is localized in neurites and growth cones; at later stages, the protein is enriched in dendritic spines and PSDs, as are components of a trimeric complex consisting of Abi-1, Eps8 and Sos-1. |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | MARK AS OVER ANNOTATED | Summary: HDA annotation from an E-cadherin cytoplasmic-tail BioID proximity biotinylation screen (PMID:25468996). Reason: Proximity biotinylation (~10-20 nm radius) identifies proteins in the adherens junction neighborhood, where the WRC regulates cortical actin, rather than demonstrating direct binary cadherin binding by ABI1. Supporting Evidence: PMID:25468996 We used proximity biotinylation and quantitative proteomics to identify 561 proteins in the vicinity of the cytoplasmic tail of E-cadherin. |
| GO:0061098 positive regulation of protein tyrosine kinase activity | IDA PMID:17101133 NESH (Abi-3) is present in the Abi/WAVE complex but does not... | ACCEPT | Summary: IDA annotation from PMID:17101133 (abstract-only in local cache) for ABI1's core role in promoting c-Abl tyrosine kinase phosphorylation of Mena and WAVE2. Reason: PMID:17101133 is abstract-only in the local cache (full_text_available: false), where its abstract reports that Abi-1 and Abi-2, unlike NESH (Abi-3), promote c-Abl-mediated phosphorylation of Mena and WAVE2. As the core Biological Process counterpart of GO:0030296 (protein tyrosine kinase activator activity, ACCEPT), this row aligns with the C-terminal SH3 requirement for Abl binding established in 99%-identical mouse ortholog Abi-1 (PMID:7590237) together with chimera/domain-swap assays on the 451-aa human ABI1/AblBP4 construct in 293T cells showing that human ABI1's SH3 domain alone is insufficient for c-Abl binding without its upstream central inter-domain spacer/linker region between the proline-rich regions and SH3 domain (amino acids 270–336; PMID:26428302), enabling cellular c-Abl-mediated phosphorylation of Mena and WAVE2 (PMID:12672821, PMID:17101133, PMID:26428302), and with the PTHR10460 family review (abl_pndy_py213_s216 contributing to GO:0061098 and SUBFAMILY_ONLY scope across ABI1, ABI2, and metazoan SF0 versus loss in vertebrate ABI3/Abi3), while coexpressed full-length wild-type human ABI1 (unlike Y213F) can also mediate Y213-dependent trans-inhibition of nonmyristoylated c-Abl pY412 phosphorylation and pervanadate-induced kinase activity in human LNCaP cells (PMID:18328268). Although Mena-versus-c-Cbl substrate selectivity in PMID:12672821 ('promoted c-Abl-mediated tyrosine phosphorylation of Mena but not other substrates such as c-Cbl') is also compatible with GO:0035591 adaptor-mediated substrate presentation (the reading adopted for GO:0061098 KEEP_AS_NON_CORE in mouse Abi2), ACCEPT is retained by direct deference to the curator's full-text IDA evaluation of this row's source paper alongside the companion abstract-only mouse GO:0030296 IDA curation on PMID:12672821, noting mouse Abi2 for future family-level harmonization. Supporting Evidence: PMID:7590237 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. PMID:12672821 Importantly, Abi-1 dramatically promoted c-Abl-mediated tyrosine phosphorylation of Mena but not other substrates such as c-Cbl. 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:26428302 This finding showed that the SH3 domain of Abi-1 was functionally replaced by the SH3 domain of NESH/Abi-3, and that the SH3 domain of Abi-1 alone was insufficient for the binding to c-Abl. PMID:26428302 Structural studies showed that a linker region between the proline-rich regions and the Src homology 3 (SH3) domain of Abi-1 is crucial for its interaction with c-Abl and c-Abl-mediated phosphorylation of WAVE2. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | MARK AS OVER ANNOTATED | Summary: HDA annotation from shotgun LC-MS/MS proteomics of human urinary exosomes (PMID:19056867). Reason: Abundant cytosolic and cortical actin-associated proteins are passively captured in shed extracellular vesicles; urinary exosome detection does not represent a functional site of ABI1 action. Supporting Evidence: PMID:19056867 Here, we used LC-MS/MS to profile the proteome of human urinary exosomes. |
| GO:0098858 actin-based cell projection | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation from PTN000048906 for active localization in actin-based cell projections. Reason: Directly supported by human ABI1 localization and function at lamellipodia and filopodia tips (PMID:11516653, PMID:15048123). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000048906 · Ancestral ABI family node SUPPORTS TRANSFER Seeded directly by human ABI1, ABI2, and Drosophila Abi 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. PMID:15048123 Consistently, inhibition of Abi1 by RNA interference (RNAi) abrogates Rac-dependent lamellipodia protrusion. |
Loading supporting content…
Download this section (compressed HTML)Q: How is cellular ABI1 partitioned dynamically between the heteropentameric WRC, the EPS8-ABI1-SOS1 Rac-GEF complex, and N-WASP endocytic assemblies within the same cell?
Q: Under what physiological stimuli does ABI1 switch between linker/SH3-mediated c-Abl substrate co-activation and pY213/PXXP-mediated trans-inhibition of nonmyristoylated c-Abl?
Q: How does alternative splicing of exon 10 remodel Rac1 engagement on intact human ABI1-containing WAVE regulatory complexes structurally?
Experiment: Quantitative endogenous SEC-MS and cross-linking MS in resting versus EGF/PDGF-stimulated human cells to measure stoichiometric partitioning of ABI1 across WRC, EPS8-SOS1, and N-WASP complexes.
Experiment: Cryo-EM reconstruction of full-length human ABI1-WRC bound to c-Abl SH3-SH2-kinase module to resolve simultaneous substrate presentation and pY213 allosteric regulation.
Experiment: Isogenic CRISPR splice-switching of ABI1 exon 10 in human epithelial and myeloid cells paired with live-cell Rac1-FRET, lamellipodial kymography, and dextran macropinocytosis assays.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)