{"gene":"SRGAP3","run_date":"2026-06-10T07:46:41","timeline":{"discoveries":[{"year":2002,"finding":"WRP (SRGAP3) was identified as a component of the WAVE-1 signaling complex via tandem mass spectrometry. WRP binds directly to WAVE-1 through its SH3 domain and functions as a Rac-selective GTPase-activating protein that attenuates Rac signaling, acting as a signal termination factor for Rac within the WAVE-1 complex.","method":"Tandem mass spectrometry, direct binding assay (SH3 domain interaction), in vivo Rac activity assay","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct binding demonstrated, in vivo functional inhibition shown, replicated in subsequent studies","pmids":["12447388"],"is_preprint":false},{"year":2002,"finding":"MEGAP/srGAP3 (isoforms a and b) functions as a GTPase-activating protein (GAP) in vitro, as demonstrated by in vitro GAP assay, and acts downstream of the Slit-Robo pathway to regulate neuronal migration and axonal branching.","method":"In vitro GAP assay, FISH, LOH analysis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — in vitro GAP activity established biochemically; pathway placement (Slit-Robo) cited from prior work rather than directly demonstrated in this paper","pmids":["12195014"],"is_preprint":false},{"year":2006,"finding":"MEGAP/srGAP3 negatively regulates cell migration by perturbing actin and microtubule cytoskeleton dynamics and hindering focal complex formation. The GAP domain (residue R542) is required for this function, as R542I missense mutation abolishes effects on actin, microtubule remodeling, and cell migration. Constitutively active Rac1 and Cdc42 rescue the loss of filopodia/lamellipodia caused by MEGAP overexpression.","method":"Inducible expression in SH-SY5Y neuroblastoma cells, time-lapse microscopy, active-site mutagenesis (R542I), epistasis with constitutively active Rac1/Cdc42","journal":"Experimental cell research","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — GAP domain mutagenesis with functional rescue, quantitative migration/protrusion assays, orthogonal methods in single lab","pmids":["16730001"],"is_preprint":false},{"year":2007,"finding":"WRP (SRGAP3) anchoring to WAVE-1 is required for normal dendritic spine density, synaptic plasticity, and cognitive behavior. Gene targeting in mice disrupting WRP-WAVE-1 interaction demonstrated that this complex is a homeostatic mechanism for neuronal development and synaptic connectivity.","method":"Neuronal time-lapse imaging, behavioral analyses, electrophysiological recordings, gene targeting in mice","journal":"The Journal of neuroscience","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic loss-of-function in vivo with multiple orthogonal readouts (morphology, electrophysiology, behavior)","pmids":["17215396"],"is_preprint":false},{"year":2011,"finding":"srGAP3 interacts with lamellipodin at the leading edge of cellular protrusions. The F-BAR domain localizes srGAP3 to the leading edge while the SH3 domain targets srGAP3 to focal adhesions. srGAP3 inhibits lamellipodin-evoked lamellipodial dynamics, and knockout fibroblasts display increased cell area and lamellipodia formation rescued by lamellipodin knockdown.","method":"Co-immunoprecipitation, live-cell imaging, domain localization studies, srGAP3 knockout MEFs, shRNA knockdown of lamellipodin","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction demonstrated, domain-function mapping, KO phenotype with genetic rescue, multiple methods in single lab","pmids":["22159416"],"is_preprint":false},{"year":2011,"finding":"srGAP3 interacts with Robo1 and Robo2 (Slit receptors), co-localizing with Robo1 in the ventral/lateral funiculus and Robo2 in the lateral funiculus of the spinal cord. Loss of srGAP3 in KO mice causes thickening of the ventral funiculus and thinning of the lateral funiculus, indicating a role in lateral positioning of post-crossing commissural axons.","method":"Co-immunoprecipitation, immunohistochemistry, axon tracing in KO mice","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP of endogenous proteins confirmed, KO phenotype with anatomical readout, single lab","pmids":["21655271"],"is_preprint":false},{"year":2011,"finding":"srGAP3 selectively binds to the activated (GTP-bound) form of Rac1 via RhoGAP domain pulldown. Overexpression of srGAP3 inhibits neuronal differentiation in a Rac1-dependent and GAP domain-dependent manner (R542A mutation abolishes effect), and constitutively active Rac1 rescues srGAP3-mediated inhibition of differentiation.","method":"RhoGAP pulldown assay, overexpression/knockdown in Neuro2A cells, active-site mutagenesis (R542A), epistasis with CA-Rac1","journal":"Cellular and molecular neurobiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical Rac1-GTP binding, mutagenesis, and genetic epistasis in single lab","pmids":["21350945"],"is_preprint":false},{"year":2012,"finding":"The F-BAR domain of srGAP3 (F-BAR3) induces filopodia formation in COS7 cells and cortical neurons, though less potently than srGAP2. F-BAR domains of srGAP1, 2, and 3 can heterodimerize. F-BAR3 displays slower molecular dynamics at the plasma membrane than F-BAR2 as measured by FRAP, correlating with reduced filopodia induction potency.","method":"Live-cell imaging in COS7 and cortical neurons, FRAP, heterodimerization assay","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct membrane dynamics measurement by FRAP, functional filopodia assay, domain-level analysis in single lab","pmids":["22467852"],"is_preprint":false},{"year":2012,"finding":"Loss of Wrp/Srgap3 in mice results in abnormal migration of neural progenitor cells from the ventricular niche into the corpus callosum, aberrant astroglial differentiation, periventricular lesions, and obstructive hydrocephalus due to cerebral aqueductal occlusion.","method":"Srgap3 knockout mice, lineage tracing, histology, MRI","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — defined cellular mechanism (abnormal progenitor migration) with lineage tracing in KO mouse, single lab","pmids":["23007397"],"is_preprint":false},{"year":2012,"finding":"Srgap3 knockout mice show increased basal Rac1 activity, enlarged lateral ventricles, abnormal dendritic spines, and complex behavioral deficits (impaired spontaneous alternation, social behavior, prepulse inhibition), establishing srGAP3 as a negative regulator of Rac1 activity in vivo during brain development.","method":"Srgap3 KO mice, Rac1 activity assay, behavioral testing, neuroanatomical analysis","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo KO with Rac1 activity measurement and multiple phenotypic readouts, single lab","pmids":["22820399"],"is_preprint":false},{"year":2012,"finding":"srGAP3 functions as a tumor suppressor in mammary epithelial cells by negatively regulating Rac1. Re-expression of srGAP3 (but not GAP-dead mutant) in breast cancer lines inhibits anchorage-independent growth and invasion, accompanied by increased ERM and MLC2 phosphorylation, and ROCK inhibition restores invasion, placing srGAP3 upstream of Rac1 and downstream Rho/ROCK signaling.","method":"RNAi knockdown, re-expression with GAP-dead mutant, anchorage-independent growth assay, invasion assay, phosphorylation analysis, ROCK inhibition","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mutagenesis (GAP-dead), multiple functional assays, pharmacological epistasis, single lab","pmids":["23108406"],"is_preprint":false},{"year":2013,"finding":"srGAP3 inhibits neuronal differentiation downstream of Slit-Robo signaling; inhibition of Slit-Robo interaction phenocopies srGAP3 loss-of-function, and srGAP3-Rac1 signaling is required for the inhibitory effect of srGAP1 and srGAP2 on neuronal differentiation.","method":"Overexpression/knockdown in Neuro2A cells, Slit-Robo pathway inhibition, GAP-dead mutants (srGAP1 R542A, srGAP2 R527A), epistasis experiments","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with pathway inhibition and domain mutants, single lab","pmids":["23505444"],"is_preprint":false},{"year":2014,"finding":"Nuclear-localized srGAP3 interacts with the SWI/SNF chromatin remodeling factor Brg1. This interaction is mediated by the C-terminal region of srGAP3 and the ATPase motif of Brg1. The interaction influences dendrite complexity in primary cortical neurons and VPA-induced neuronal differentiation in Neuro2A cells. GTP-bound Rac1 and GAP-43 are identified as potential mediators of the nuclear srGAP3-Brg1 interaction.","method":"Co-immunoprecipitation, domain deletion mapping, neuronal morphology analysis, Neuro2A differentiation assay","journal":"Molecular and cellular neurosciences","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — Co-IP with domain mapping, functional neuronal readout, nuclear localization of srGAP3 established, single lab","pmids":["24561795"],"is_preprint":false},{"year":2014,"finding":"srGAP3 interacts with Robo2 and Slit1, and this interaction decreases Rac1-GTP activity in dorsal root ganglion neurons, promoting neurite outgrowth and filopodial growth cone formation.","method":"Co-immunoprecipitation, immunoblotting for Rac1-GTP, anti-srGAP3/Robo2 antibody inhibition of neurite outgrowth","journal":"Asian Pacific journal of tropical medicine","confidence":"Low","confidence_rationale":"Tier 3 / Weak — Co-IP performed but methods less rigorous, single lab, limited orthogonal validation","pmids":["25149377"],"is_preprint":false},{"year":2015,"finding":"The C-terminal region (CTR) of srGAP3 contains a single PXXP proline-rich motif that mediates binding to SH3 domains of endocytic proteins Amphiphysin, Endophilin-A2, Endophilin-A1, and the Ras signaling protein Grb2, potentially linking receptor signaling to the endocytic machinery.","method":"Pulldown assay, mutational analysis of PXXP motif, SH3 domain binding assay","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — single PXXP motif mapped by mutagenesis, multiple binding partners confirmed, single lab","pmids":["25819436"],"is_preprint":false},{"year":2020,"finding":"In spinal cord dorsal horn during neuropathic pain, increased srGAP3 promotes new immature dendritic spine formation in the initiation phase, while decreased srGAP3 in the maintenance phase leads to elevated Rac1-GTP activity, actin polymerization, and dendritic spine maturation. srGAP3 siRNA during initiation phase, and Rac1 inhibitor during maintenance phase, each independently attenuate neuropathic pain, and combined targeting produces optimal analgesia.","method":"srGAP3 siRNA, Rac1 inhibitor, Western blotting for Rac1-GTP, Golgi staining for dendritic spines, behavioral assays in paclitaxel neuropathy model","journal":"The Journal of physiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic knockdown with pharmacological epistasis, multiple phenotypic and biochemical readouts, single lab","pmids":["32237255"],"is_preprint":false}],"current_model":"SRGAP3 (WRP/MEGAP) is a Rac1-selective RhoGAP that terminates Rac signaling by binding WAVE-1 through its SH3 domain to form a signal termination complex; its F-BAR domain drives membrane deformation and filopodia formation while its C-terminal PXXP motif connects it to endocytic machinery; it acts downstream of Slit-Robo signaling to regulate actin cytoskeletal dynamics, dendritic spine morphogenesis, cell migration, neuronal differentiation, and commissural axon positioning, with nuclear pools of srGAP3 additionally interacting with the chromatin remodeler Brg1 to regulate gene expression during neuronal development."},"narrative":{"mechanistic_narrative":"SRGAP3 (WRP/MEGAP) is a Rac1-selective RhoGAP that couples Slit-Robo guidance signaling to actin cytoskeletal remodeling, governing neuronal migration, dendritic spine morphogenesis, neuronal differentiation, and cell migration [PMID:12447388, PMID:12195014, PMID:22820399]. It binds the activated GTP-bound form of Rac1 through its RhoGAP domain and accelerates GTP hydrolysis; the catalytic arginine (R542) is essential, as its mutation abolishes effects on actin and microtubule dynamics, cell migration, and neuronal differentiation [PMID:16730001, PMID:21350945]. Through its SH3 domain SRGAP3 binds WAVE-1 to form a Rac signal-termination complex, an anchoring that is required in vivo for normal dendritic spine density, synaptic plasticity, and cognitive behavior [PMID:12447388, PMID:17215396]. Its F-BAR domain deforms membrane to localize the protein to the leading edge and induce filopodia, while the SH3 domain targets it to focal adhesions, and a C-terminal PXXP motif links it to endocytic SH3 proteins (Amphiphysin, Endophilin-A1/A2) and Grb2 [PMID:22159416, PMID:22467852, PMID:25819436]. SRGAP3 acts downstream of Slit-Robo, interacting with Robo1/Robo2 to position post-crossing commissural axons and to suppress neuronal differentiation through Rac1 [PMID:21655271, PMID:23505444], and a nuclear pool engages the SWI/SNF ATPase Brg1 to influence dendrite complexity and differentiation [PMID:24561795]. Loss of Srgap3 in mice elevates basal Rac1 activity and produces aberrant neural progenitor migration, hydrocephalus, abnormal spines, and behavioral deficits [PMID:23007397, PMID:22820399]. Beyond these neural roles it acts as a Rac1-suppressing tumor suppressor in mammary epithelium, restraining anchorage-independent growth and invasion via downstream Rho/ROCK signaling [PMID:23108406].","teleology":[{"year":2002,"claim":"Established SRGAP3 as a Rac-selective GAP and defined its molecular context by placing it within the WAVE-1 complex as a Rac signal-termination factor, answering how Rac signaling is locally attenuated.","evidence":"Tandem mass spectrometry, SH3-domain direct binding assay, and in vivo Rac activity assay identifying WRP in the WAVE-1 complex; parallel in vitro GAP assay for MEGAP/srGAP3","pmids":["12447388","12195014"],"confidence":"High","gaps":["Slit-Robo pathway placement cited from prior work rather than directly demonstrated","structural basis of SH3-WAVE-1 binding not resolved"]},{"year":2006,"claim":"Demonstrated that catalytic GAP activity is required for SRGAP3's control of cytoskeletal dynamics and migration, linking enzymatic function to phenotype through the R542 active-site residue.","evidence":"Inducible expression in SH-SY5Y cells, time-lapse microscopy, R542I active-site mutagenesis, and epistasis rescue with constitutively active Rac1/Cdc42","pmids":["16730001"],"confidence":"High","gaps":["mechanism of microtubule and focal-complex effects relative to direct Rac GAP activity not separated","single cell-line context"]},{"year":2007,"claim":"Showed in vivo that the SRGAP3-WAVE-1 interaction is a homeostatic requirement for synaptic connectivity and cognition, elevating the biochemical complex to a developmental mechanism.","evidence":"Gene targeting in mice disrupting WRP-WAVE-1 binding with imaging, electrophysiology, and behavioral readouts","pmids":["17215396"],"confidence":"High","gaps":["does not isolate WAVE-1-dependent from WAVE-1-independent SRGAP3 functions in vivo"]},{"year":2011,"claim":"Resolved domain-level division of labor — F-BAR targets the leading edge and SH3 targets focal adhesions — and identified lamellipodin and Robo1/Robo2 as physical partners controlling protrusion and axon positioning.","evidence":"Co-immunoprecipitation, live-cell imaging, domain localization, srGAP3 KO MEFs with lamellipodin rescue, immunohistochemistry, and axon tracing in KO mice","pmids":["22159416","21655271","21350945"],"confidence":"Medium","gaps":["how F-BAR and SH3 localizations are coordinated in a single molecule unresolved","direct Robo-to-Rac signaling chain not reconstituted"]},{"year":2012,"claim":"Established SRGAP3 as a negative regulator of Rac1 in vivo during brain development and as a tumor suppressor, broadening its role from neurons to epithelial growth control, and characterized F-BAR-driven filopodia induction.","evidence":"Srgap3 KO mice with Rac1 activity assays, lineage tracing, histology/MRI; breast cancer re-expression with GAP-dead mutant and ROCK inhibition; F-BAR FRAP and heterodimerization assays","pmids":["23007397","22820399","23108406","22467852"],"confidence":"Medium","gaps":["tumor suppressor mechanism (Rac1 vs Rho/ROCK balance) not fully dissected","F-BAR filopodia potency differences mechanistically unexplained"]},{"year":2013,"claim":"Placed SRGAP3-Rac1 signaling downstream of Slit-Robo as an inhibitor of neuronal differentiation, integrating the GAP into a defined guidance pathway shared with srGAP1/2.","evidence":"Overexpression/knockdown in Neuro2A cells, Slit-Robo pathway inhibition, and GAP-dead mutant epistasis","pmids":["23505444"],"confidence":"Medium","gaps":["direct Robo-to-srGAP3 activation step not biochemically demonstrated"]},{"year":2014,"claim":"Identified a nuclear function for SRGAP3 through interaction with the SWI/SNF ATPase Brg1, suggesting a route by which a cytoskeletal GAP influences gene-regulatory programs.","evidence":"Co-immunoprecipitation, domain deletion mapping (C-terminus / Brg1 ATPase motif), neuronal morphology and Neuro2A differentiation assays","pmids":["24561795"],"confidence":"Medium","gaps":["target genes regulated by nuclear srGAP3-Brg1 not identified","Rac1/GAP-43 as mediators only proposed, not mechanistically established"]},{"year":2015,"claim":"Mapped a single C-terminal PXXP motif that links SRGAP3 to endocytic SH3 proteins and Grb2, providing a candidate connection between receptor signaling and membrane trafficking.","evidence":"Pulldown and PXXP mutational analysis against SH3 domains of Amphiphysin, Endophilin-A1/A2, and Grb2","pmids":["25819436"],"confidence":"Medium","gaps":["functional consequence of endocytic coupling in cells not demonstrated","no in vivo validation"]},{"year":2020,"claim":"Demonstrated phase-specific regulation of dendritic spines by SRGAP3 in neuropathic pain, showing that its level dynamically tunes Rac1 activity to control spine maturation and pain behavior.","evidence":"srGAP3 siRNA and Rac1 inhibitor with Rac1-GTP Western blotting, Golgi spine staining, and behavioral assays in a paclitaxel neuropathy model","pmids":["32237255"],"confidence":"Medium","gaps":["upstream control of srGAP3 level across pain phases unknown","single model and lab"]},{"year":null,"claim":"It remains unresolved how SRGAP3's distinct domain activities (F-BAR membrane deformation, GAP catalysis, SH3/PXXP partner binding, and nuclear Brg1 engagement) are spatially and temporally coordinated within a single signaling event, and what gene-regulatory targets the nuclear pool controls.","evidence":"","pmids":[],"confidence":"Low","gaps":["no integrated structural/regulatory model across domains","nuclear transcriptional targets uncharacterized","regulation of SRGAP3 abundance and localization not defined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0,2,6,10]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,9,6]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[2,4,7]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[4,7]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,14]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[4,7]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[12]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[2,4]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,5,11]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[3,8,5]},{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[3,9,15]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[10]}],"complexes":["WAVE-1 complex"],"partners":["WASF1","ROBO1","ROBO2","RAC1","RAPH1","SMARCA4","GRB2","AMPH"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O43295","full_name":"SLIT-ROBO Rho GTPase-activating protein 3","aliases":["Mental disorder-associated GAP","Rho GTPase-activating protein 14","WAVE-associated Rac GTPase-activating protein","WRP"],"length_aa":1099,"mass_kda":124.5,"function":"GTPase-activating protein for RAC1 and perhaps Cdc42, but not for RhoA small GTPase. May attenuate RAC1 signaling in neurons","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/O43295/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SRGAP3","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CALD1","stoichiometry":0.2},{"gene":"CALM3","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/SRGAP3","total_profiled":1310},"omim":[{"mim_id":"613792","title":"CHROMOSOME 3pter-p25 DELETION SYNDROME","url":"https://www.omim.org/entry/613792"},{"mim_id":"606525","title":"SLIT-ROBO RHO GTPase-ACTIVATING PROTEIN 3; SRGAP3","url":"https://www.omim.org/entry/606525"},{"mim_id":"606524","title":"SLIT-ROBO RHO GTPase-ACTIVATING PROTEIN 2; SRGAP2","url":"https://www.omim.org/entry/606524"},{"mim_id":"606523","title":"SLIT-ROBO RHO GTPase-ACTIVATING PROTEIN 1; SRGAP1","url":"https://www.omim.org/entry/606523"},{"mim_id":"168600","title":"PARKINSON DISEASE, LATE-ONSET; PD","url":"https://www.omim.org/entry/168600"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cytosol","reliability":"Approved"},{"location":"Centrosome","reliability":"Additional"},{"location":"Basal body","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"brain","ntpm":35.0}],"url":"https://www.proteinatlas.org/search/SRGAP3"},"hgnc":{"alias_symbol":["KIAA0411","MEGAP","WRP","ARHGAP14"],"prev_symbol":["SRGAP2"]},"alphafold":{"accession":"O43295","domains":[{"cath_id":"-","chopping":"9-83_90-161_270-295","consensus_level":"high","plddt":93.9606,"start":9,"end":295},{"cath_id":"1.10.555.10","chopping":"507-692","consensus_level":"high","plddt":91.0461,"start":507,"end":692},{"cath_id":"2.30.30.40","chopping":"746-799","consensus_level":"high","plddt":91.1656,"start":746,"end":799},{"cath_id":"1.20.20","chopping":"348-391_426-467","consensus_level":"medium","plddt":94.43,"start":348,"end":467}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O43295","model_url":"https://alphafold.ebi.ac.uk/files/AF-O43295-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O43295-F1-predicted_aligned_error_v6.png","plddt_mean":71.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SRGAP3","jax_strain_url":"https://www.jax.org/strain/search?query=SRGAP3"},"sequence":{"accession":"O43295","fasta_url":"https://rest.uniprot.org/uniprotkb/O43295.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O43295/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O43295"}},"corpus_meta":[{"pmid":"17215396","id":"PMC_17215396","title":"A WAVE-1 and WRP signaling complex regulates spine density, synaptic plasticity, and memory.","date":"2007","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/17215396","citation_count":178,"is_preprint":false},{"pmid":"12195014","id":"PMC_12195014","title":"The novel Rho-GTPase activating gene MEGAP/ srGAP3 has a putative role in severe mental retardation.","date":"2002","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/12195014","citation_count":174,"is_preprint":false},{"pmid":"12447388","id":"PMC_12447388","title":"The WRP component of the WAVE-1 complex attenuates Rac-mediated signalling.","date":"2002","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/12447388","citation_count":166,"is_preprint":false},{"pmid":"22467852","id":"PMC_22467852","title":"The F-BAR domains from srGAP1, srGAP2 and srGAP3 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medicine","url":"https://pubmed.ncbi.nlm.nih.gov/25149377","citation_count":7,"is_preprint":false},{"pmid":"37211600","id":"PMC_37211600","title":"Electroacupuncture inhibits dendritic spine remodeling through the srGAP3-Rac1 signaling pathway in rats with SNL.","date":"2023","source":"Biological research","url":"https://pubmed.ncbi.nlm.nih.gov/37211600","citation_count":4,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.05.15.654213","title":"Explainable AI-Driven Diagnosis Model for Early Glaucoma Detection Using Grey-Wolf Optimized Extreme Learning Machine 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WRP binds directly to WAVE-1 through its SH3 domain and functions as a Rac-selective GTPase-activating protein that attenuates Rac signaling, acting as a signal termination factor for Rac within the WAVE-1 complex.\",\n      \"method\": \"Tandem mass spectrometry, direct binding assay (SH3 domain interaction), in vivo Rac activity assay\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct binding demonstrated, in vivo functional inhibition shown, replicated in subsequent studies\",\n      \"pmids\": [\"12447388\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"MEGAP/srGAP3 (isoforms a and b) functions as a GTPase-activating protein (GAP) in vitro, as demonstrated by in vitro GAP assay, and acts downstream of the Slit-Robo pathway to regulate neuronal migration and axonal branching.\",\n      \"method\": \"In vitro GAP assay, FISH, LOH analysis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro GAP activity established biochemically; pathway placement (Slit-Robo) cited from prior work rather than directly demonstrated in this paper\",\n      \"pmids\": [\"12195014\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"MEGAP/srGAP3 negatively regulates cell migration by perturbing actin and microtubule cytoskeleton dynamics and hindering focal complex formation. The GAP domain (residue R542) is required for this function, as R542I missense mutation abolishes effects on actin, microtubule remodeling, and cell migration. Constitutively active Rac1 and Cdc42 rescue the loss of filopodia/lamellipodia caused by MEGAP overexpression.\",\n      \"method\": \"Inducible expression in SH-SY5Y neuroblastoma cells, time-lapse microscopy, active-site mutagenesis (R542I), epistasis with constitutively active Rac1/Cdc42\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — GAP domain mutagenesis with functional rescue, quantitative migration/protrusion assays, orthogonal methods in single lab\",\n      \"pmids\": [\"16730001\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"WRP (SRGAP3) anchoring to WAVE-1 is required for normal dendritic spine density, synaptic plasticity, and cognitive behavior. Gene targeting in mice disrupting WRP-WAVE-1 interaction demonstrated that this complex is a homeostatic mechanism for neuronal development and synaptic connectivity.\",\n      \"method\": \"Neuronal time-lapse imaging, behavioral analyses, electrophysiological recordings, gene targeting in mice\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic loss-of-function in vivo with multiple orthogonal readouts (morphology, electrophysiology, behavior)\",\n      \"pmids\": [\"17215396\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"srGAP3 interacts with lamellipodin at the leading edge of cellular protrusions. The F-BAR domain localizes srGAP3 to the leading edge while the SH3 domain targets srGAP3 to focal adhesions. srGAP3 inhibits lamellipodin-evoked lamellipodial dynamics, and knockout fibroblasts display increased cell area and lamellipodia formation rescued by lamellipodin knockdown.\",\n      \"method\": \"Co-immunoprecipitation, live-cell imaging, domain localization studies, srGAP3 knockout MEFs, shRNA knockdown of lamellipodin\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction demonstrated, domain-function mapping, KO phenotype with genetic rescue, multiple methods in single lab\",\n      \"pmids\": [\"22159416\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"srGAP3 interacts with Robo1 and Robo2 (Slit receptors), co-localizing with Robo1 in the ventral/lateral funiculus and Robo2 in the lateral funiculus of the spinal cord. Loss of srGAP3 in KO mice causes thickening of the ventral funiculus and thinning of the lateral funiculus, indicating a role in lateral positioning of post-crossing commissural axons.\",\n      \"method\": \"Co-immunoprecipitation, immunohistochemistry, axon tracing in KO mice\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP of endogenous proteins confirmed, KO phenotype with anatomical readout, single lab\",\n      \"pmids\": [\"21655271\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"srGAP3 selectively binds to the activated (GTP-bound) form of Rac1 via RhoGAP domain pulldown. Overexpression of srGAP3 inhibits neuronal differentiation in a Rac1-dependent and GAP domain-dependent manner (R542A mutation abolishes effect), and constitutively active Rac1 rescues srGAP3-mediated inhibition of differentiation.\",\n      \"method\": \"RhoGAP pulldown assay, overexpression/knockdown in Neuro2A cells, active-site mutagenesis (R542A), epistasis with CA-Rac1\",\n      \"journal\": \"Cellular and molecular neurobiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical Rac1-GTP binding, mutagenesis, and genetic epistasis in single lab\",\n      \"pmids\": [\"21350945\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"The F-BAR domain of srGAP3 (F-BAR3) induces filopodia formation in COS7 cells and cortical neurons, though less potently than srGAP2. F-BAR domains of srGAP1, 2, and 3 can heterodimerize. F-BAR3 displays slower molecular dynamics at the plasma membrane than F-BAR2 as measured by FRAP, correlating with reduced filopodia induction potency.\",\n      \"method\": \"Live-cell imaging in COS7 and cortical neurons, FRAP, heterodimerization assay\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct membrane dynamics measurement by FRAP, functional filopodia assay, domain-level analysis in single lab\",\n      \"pmids\": [\"22467852\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Loss of Wrp/Srgap3 in mice results in abnormal migration of neural progenitor cells from the ventricular niche into the corpus callosum, aberrant astroglial differentiation, periventricular lesions, and obstructive hydrocephalus due to cerebral aqueductal occlusion.\",\n      \"method\": \"Srgap3 knockout mice, lineage tracing, histology, MRI\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — defined cellular mechanism (abnormal progenitor migration) with lineage tracing in KO mouse, single lab\",\n      \"pmids\": [\"23007397\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Srgap3 knockout mice show increased basal Rac1 activity, enlarged lateral ventricles, abnormal dendritic spines, and complex behavioral deficits (impaired spontaneous alternation, social behavior, prepulse inhibition), establishing srGAP3 as a negative regulator of Rac1 activity in vivo during brain development.\",\n      \"method\": \"Srgap3 KO mice, Rac1 activity assay, behavioral testing, neuroanatomical analysis\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo KO with Rac1 activity measurement and multiple phenotypic readouts, single lab\",\n      \"pmids\": [\"22820399\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"srGAP3 functions as a tumor suppressor in mammary epithelial cells by negatively regulating Rac1. Re-expression of srGAP3 (but not GAP-dead mutant) in breast cancer lines inhibits anchorage-independent growth and invasion, accompanied by increased ERM and MLC2 phosphorylation, and ROCK inhibition restores invasion, placing srGAP3 upstream of Rac1 and downstream Rho/ROCK signaling.\",\n      \"method\": \"RNAi knockdown, re-expression with GAP-dead mutant, anchorage-independent growth assay, invasion assay, phosphorylation analysis, ROCK inhibition\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutagenesis (GAP-dead), multiple functional assays, pharmacological epistasis, single lab\",\n      \"pmids\": [\"23108406\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"srGAP3 inhibits neuronal differentiation downstream of Slit-Robo signaling; inhibition of Slit-Robo interaction phenocopies srGAP3 loss-of-function, and srGAP3-Rac1 signaling is required for the inhibitory effect of srGAP1 and srGAP2 on neuronal differentiation.\",\n      \"method\": \"Overexpression/knockdown in Neuro2A cells, Slit-Robo pathway inhibition, GAP-dead mutants (srGAP1 R542A, srGAP2 R527A), epistasis experiments\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with pathway inhibition and domain mutants, single lab\",\n      \"pmids\": [\"23505444\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Nuclear-localized srGAP3 interacts with the SWI/SNF chromatin remodeling factor Brg1. This interaction is mediated by the C-terminal region of srGAP3 and the ATPase motif of Brg1. The interaction influences dendrite complexity in primary cortical neurons and VPA-induced neuronal differentiation in Neuro2A cells. GTP-bound Rac1 and GAP-43 are identified as potential mediators of the nuclear srGAP3-Brg1 interaction.\",\n      \"method\": \"Co-immunoprecipitation, domain deletion mapping, neuronal morphology analysis, Neuro2A differentiation assay\",\n      \"journal\": \"Molecular and cellular neurosciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — Co-IP with domain mapping, functional neuronal readout, nuclear localization of srGAP3 established, single lab\",\n      \"pmids\": [\"24561795\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"srGAP3 interacts with Robo2 and Slit1, and this interaction decreases Rac1-GTP activity in dorsal root ganglion neurons, promoting neurite outgrowth and filopodial growth cone formation.\",\n      \"method\": \"Co-immunoprecipitation, immunoblotting for Rac1-GTP, anti-srGAP3/Robo2 antibody inhibition of neurite outgrowth\",\n      \"journal\": \"Asian Pacific journal of tropical medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — Co-IP performed but methods less rigorous, single lab, limited orthogonal validation\",\n      \"pmids\": [\"25149377\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The C-terminal region (CTR) of srGAP3 contains a single PXXP proline-rich motif that mediates binding to SH3 domains of endocytic proteins Amphiphysin, Endophilin-A2, Endophilin-A1, and the Ras signaling protein Grb2, potentially linking receptor signaling to the endocytic machinery.\",\n      \"method\": \"Pulldown assay, mutational analysis of PXXP motif, SH3 domain binding assay\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — single PXXP motif mapped by mutagenesis, multiple binding partners confirmed, single lab\",\n      \"pmids\": [\"25819436\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In spinal cord dorsal horn during neuropathic pain, increased srGAP3 promotes new immature dendritic spine formation in the initiation phase, while decreased srGAP3 in the maintenance phase leads to elevated Rac1-GTP activity, actin polymerization, and dendritic spine maturation. srGAP3 siRNA during initiation phase, and Rac1 inhibitor during maintenance phase, each independently attenuate neuropathic pain, and combined targeting produces optimal analgesia.\",\n      \"method\": \"srGAP3 siRNA, Rac1 inhibitor, Western blotting for Rac1-GTP, Golgi staining for dendritic spines, behavioral assays in paclitaxel neuropathy model\",\n      \"journal\": \"The Journal of physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic knockdown with pharmacological epistasis, multiple phenotypic and biochemical readouts, single lab\",\n      \"pmids\": [\"32237255\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SRGAP3 (WRP/MEGAP) is a Rac1-selective RhoGAP that terminates Rac signaling by binding WAVE-1 through its SH3 domain to form a signal termination complex; its F-BAR domain drives membrane deformation and filopodia formation while its C-terminal PXXP motif connects it to endocytic machinery; it acts downstream of Slit-Robo signaling to regulate actin cytoskeletal dynamics, dendritic spine morphogenesis, cell migration, neuronal differentiation, and commissural axon positioning, with nuclear pools of srGAP3 additionally interacting with the chromatin remodeler Brg1 to regulate gene expression during neuronal development.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SRGAP3 (WRP/MEGAP) is a Rac1-selective RhoGAP that couples Slit-Robo guidance signaling to actin cytoskeletal remodeling, governing neuronal migration, dendritic spine morphogenesis, neuronal differentiation, and cell migration [#0, #1, #9]. It binds the activated GTP-bound form of Rac1 through its RhoGAP domain and accelerates GTP hydrolysis; the catalytic arginine (R542) is essential, as its mutation abolishes effects on actin and microtubule dynamics, cell migration, and neuronal differentiation [#2, #6]. Through its SH3 domain SRGAP3 binds WAVE-1 to form a Rac signal-termination complex, an anchoring that is required in vivo for normal dendritic spine density, synaptic plasticity, and cognitive behavior [#0, #3]. Its F-BAR domain deforms membrane to localize the protein to the leading edge and induce filopodia, while the SH3 domain targets it to focal adhesions, and a C-terminal PXXP motif links it to endocytic SH3 proteins (Amphiphysin, Endophilin-A1/A2) and Grb2 [#4, #7, #14]. SRGAP3 acts downstream of Slit-Robo, interacting with Robo1/Robo2 to position post-crossing commissural axons and to suppress neuronal differentiation through Rac1 [#5, #11], and a nuclear pool engages the SWI/SNF ATPase Brg1 to influence dendrite complexity and differentiation [#12]. Loss of Srgap3 in mice elevates basal Rac1 activity and produces aberrant neural progenitor migration, hydrocephalus, abnormal spines, and behavioral deficits [#8, #9]. Beyond these neural roles it acts as a Rac1-suppressing tumor suppressor in mammary epithelium, restraining anchorage-independent growth and invasion via downstream Rho/ROCK signaling [#10].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Established SRGAP3 as a Rac-selective GAP and defined its molecular context by placing it within the WAVE-1 complex as a Rac signal-termination factor, answering how Rac signaling is locally attenuated.\",\n      \"evidence\": \"Tandem mass spectrometry, SH3-domain direct binding assay, and in vivo Rac activity assay identifying WRP in the WAVE-1 complex; parallel in vitro GAP assay for MEGAP/srGAP3\",\n      \"pmids\": [\"12447388\", \"12195014\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Slit-Robo pathway placement cited from prior work rather than directly demonstrated\", \"structural basis of SH3-WAVE-1 binding not resolved\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Demonstrated that catalytic GAP activity is required for SRGAP3's control of cytoskeletal dynamics and migration, linking enzymatic function to phenotype through the R542 active-site residue.\",\n      \"evidence\": \"Inducible expression in SH-SY5Y cells, time-lapse microscopy, R542I active-site mutagenesis, and epistasis rescue with constitutively active Rac1/Cdc42\",\n      \"pmids\": [\"16730001\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"mechanism of microtubule and focal-complex effects relative to direct Rac GAP activity not separated\", \"single cell-line context\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Showed in vivo that the SRGAP3-WAVE-1 interaction is a homeostatic requirement for synaptic connectivity and cognition, elevating the biochemical complex to a developmental mechanism.\",\n      \"evidence\": \"Gene targeting in mice disrupting WRP-WAVE-1 binding with imaging, electrophysiology, and behavioral readouts\",\n      \"pmids\": [\"17215396\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"does not isolate WAVE-1-dependent from WAVE-1-independent SRGAP3 functions in vivo\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Resolved domain-level division of labor — F-BAR targets the leading edge and SH3 targets focal adhesions — and identified lamellipodin and Robo1/Robo2 as physical partners controlling protrusion and axon positioning.\",\n      \"evidence\": \"Co-immunoprecipitation, live-cell imaging, domain localization, srGAP3 KO MEFs with lamellipodin rescue, immunohistochemistry, and axon tracing in KO mice\",\n      \"pmids\": [\"22159416\", \"21655271\", \"21350945\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"how F-BAR and SH3 localizations are coordinated in a single molecule unresolved\", \"direct Robo-to-Rac signaling chain not reconstituted\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Established SRGAP3 as a negative regulator of Rac1 in vivo during brain development and as a tumor suppressor, broadening its role from neurons to epithelial growth control, and characterized F-BAR-driven filopodia induction.\",\n      \"evidence\": \"Srgap3 KO mice with Rac1 activity assays, lineage tracing, histology/MRI; breast cancer re-expression with GAP-dead mutant and ROCK inhibition; F-BAR FRAP and heterodimerization assays\",\n      \"pmids\": [\"23007397\", \"22820399\", \"23108406\", \"22467852\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"tumor suppressor mechanism (Rac1 vs Rho/ROCK balance) not fully dissected\", \"F-BAR filopodia potency differences mechanistically unexplained\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Placed SRGAP3-Rac1 signaling downstream of Slit-Robo as an inhibitor of neuronal differentiation, integrating the GAP into a defined guidance pathway shared with srGAP1/2.\",\n      \"evidence\": \"Overexpression/knockdown in Neuro2A cells, Slit-Robo pathway inhibition, and GAP-dead mutant epistasis\",\n      \"pmids\": [\"23505444\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"direct Robo-to-srGAP3 activation step not biochemically demonstrated\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified a nuclear function for SRGAP3 through interaction with the SWI/SNF ATPase Brg1, suggesting a route by which a cytoskeletal GAP influences gene-regulatory programs.\",\n      \"evidence\": \"Co-immunoprecipitation, domain deletion mapping (C-terminus / Brg1 ATPase motif), neuronal morphology and Neuro2A differentiation assays\",\n      \"pmids\": [\"24561795\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"target genes regulated by nuclear srGAP3-Brg1 not identified\", \"Rac1/GAP-43 as mediators only proposed, not mechanistically established\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Mapped a single C-terminal PXXP motif that links SRGAP3 to endocytic SH3 proteins and Grb2, providing a candidate connection between receptor signaling and membrane trafficking.\",\n      \"evidence\": \"Pulldown and PXXP mutational analysis against SH3 domains of Amphiphysin, Endophilin-A1/A2, and Grb2\",\n      \"pmids\": [\"25819436\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"functional consequence of endocytic coupling in cells not demonstrated\", \"no in vivo validation\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Demonstrated phase-specific regulation of dendritic spines by SRGAP3 in neuropathic pain, showing that its level dynamically tunes Rac1 activity to control spine maturation and pain behavior.\",\n      \"evidence\": \"srGAP3 siRNA and Rac1 inhibitor with Rac1-GTP Western blotting, Golgi spine staining, and behavioral assays in a paclitaxel neuropathy model\",\n      \"pmids\": [\"32237255\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"upstream control of srGAP3 level across pain phases unknown\", \"single model and lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how SRGAP3's distinct domain activities (F-BAR membrane deformation, GAP catalysis, SH3/PXXP partner binding, and nuclear Brg1 engagement) are spatially and temporally coordinated within a single signaling event, and what gene-regulatory targets the nuclear pool controls.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"no integrated structural/regulatory model across domains\", \"nuclear transcriptional targets uncharacterized\", \"regulation of SRGAP3 abundance and localization not defined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0, 2, 6, 10]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 9, 6]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [2, 4, 7]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [4, 7]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 14]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [4, 7]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [12]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [2, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 5, 11]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [3, 8, 5]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [3, 9, 15]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"complexes\": [\n      \"WAVE-1 complex\"\n    ],\n    \"partners\": [\n      \"WASF1\",\n      \"ROBO1\",\n      \"ROBO2\",\n      \"RAC1\",\n      \"RAPH1\",\n      \"SMARCA4\",\n      \"GRB2\",\n      \"AMPH\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}