{"gene":"FNBP1","run_date":"2026-06-09T23:54:44","timeline":{"discoveries":[{"year":2018,"finding":"FBP17 and CIP4 prime the plasma membrane for fast endophilin-mediated endocytosis (FEME) by recruiting the 5'-lipid phosphatase SHIP2 and lamellipodin to mediate local production of phosphatidylinositol-3,4-bisphosphate and endophilin pre-enrichment. Membrane-bound GTP-loaded Cdc42 recruits FBP17 and CIP4, which are then locally deactivated by RICH1 and SH3BP1 GAPs, generating transient assembly and disassembly of endophilin spots.","method":"Colocalization screens of BAR domain proteins with endophilin, Co-IP, lipid phosphatase recruitment assays, live imaging of endophilin foci dynamics","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal functional assays with multiple orthogonal methods (colocalization, Co-IP, receptor activation, GAP pathway genetics) in a high-quality study","pmids":["30061681"],"is_preprint":false},{"year":2001,"finding":"FBP17 interacts with sorting nexin SNX2 as identified by yeast two-hybrid screening of a human kidney library, providing a link between the EGF receptor pathway and FBP17. FBP17 contains a C-terminal SH3 domain, an N-terminal region homologous to cdc15 (an actin cytoskeleton regulator in S. pombe), and a consensus Rho-binding motif; however, none of the Rho family proteins tested interacted with FBP17 in yeast two-hybrid assays.","method":"Yeast two-hybrid screen, domain analysis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — yeast two-hybrid identification of SNX2 interaction; negative Rho-binding result experimentally established; single lab, single method for positive interaction","pmids":["11438682"],"is_preprint":false},{"year":2009,"finding":"FBP17 recruits WASP, WIP (WASP-interacting protein), and dynamin-2 to the plasma membrane, and this recruitment is necessary for the formation of podosomes and phagocytic cups in macrophages. The N-terminal EFC/F-BAR domain of FBP17 mediates membrane binding and deformation, enabling simultaneous membrane deformation and actin polymerization at the same sites.","method":"FBP17 knockdown/overexpression, fluorescence microscopy, domain deletion constructs, podosome and phagocytic cup formation assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined cellular phenotypes, domain dissection with multiple functional readouts, single lab but multiple orthogonal methods","pmids":["19155218"],"is_preprint":false},{"year":2019,"finding":"FBP17 is recruited to caveolae to induce formation of caveolar rosettes and buffer plasma membrane tension. c-Abl tyrosine kinase directly phosphorylates the FBP17 F-BAR domain in response to mechanical tension, which inhibits FBP17 membrane-bending activity and releases FBP17-controlled inhibition of mDia1-dependent stress fibers, allowing membrane adaptation to increased mechanical tension.","method":"FBP17 knockout cells, osmotic shock assays, phosphorylation assays with c-Abl, live imaging, caveolar rosette quantification, stress fiber analysis","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (KO phenotyping, direct phosphorylation assay, functional rescue, structural domain analysis, live imaging) in a single rigorous study","pmids":["31862885"],"is_preprint":false},{"year":2011,"finding":"FBP17 localizes to invadopodia in invasive bladder tumor cells, and its knockdown decreases invadopodia formation to 13–14% of control and decreases invasive capacity to 14–16%. Both the EFC/F-BAR domain (membrane deformation) and the SH3 domain (dynamin-2 recruitment) of FBP17 are necessary for invadopodia formation and invasion.","method":"FBP17 knockdown, phalloidin staining for invadopodia, Transwell invasion assay, domain mutant constructs","journal":"The Journal of urology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined cellular phenotypes and domain dissection, single lab, multiple methods","pmids":["21421245"],"is_preprint":false},{"year":2003,"finding":"FBP17 binds to tankyrase (TNKS), an ADP-ribose polymerase involved in telomere maintenance and MAPK signaling, via a specific TNKS-binding motif in FBP17. This interaction was identified by yeast two-hybrid assay and confirmed by co-immunoprecipitation of endogenous proteins in 293T cells.","method":"Yeast two-hybrid assay, co-immunoprecipitation of endogenous proteins in 293T cells","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — binding confirmed by both yeast two-hybrid and endogenous co-IP, single lab, two complementary methods","pmids":["14596906"],"is_preprint":false},{"year":2009,"finding":"FBP17-induced membrane tubulation directs actin polymerization toward membrane tubules, suggesting that actin polymerization occurs toward the neck of endocytic vesicles during clathrin-dependent endocytosis to facilitate vesicle fission.","method":"Fluorescence imaging of actin dynamics at FBP17-induced membrane tubules","journal":"FEBS letters","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single imaging study, single lab, no mutagenesis or reconstitution; mechanistic model is largely interpretive","pmids":["19835875"],"is_preprint":false},{"year":2020,"finding":"The F-BAR domain of FBP17 alone displays minimal curvature-sensing activity in vitro. Instead, an alternatively spliced intrinsically disordered region (IDR) adjacent to the F-BAR domain has curvature-sensing ability greatly exceeding that of the F-BAR domain alone. In living cells, presence of the IDR delayed FBP17 recruitment in curvature-coupled cortical waves.","method":"Nanobar-supported lipid bilayer system for in vitro curvature sensing, live cell imaging of cortical waves","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — reconstituted in vitro curvature assay with domain mutants validated in live cells, single lab, two orthogonal methods","pmids":["33205024"],"is_preprint":false},{"year":2021,"finding":"FBP17 accumulates at the interface between RasV12-transformed and normal cells and promotes formation of finger-like membrane protrusions that mediate cell competition. Cdc42 acts upstream of FBP17 in this process. FBP17 plays a positive role in apical elimination of RasV12 cells from the epithelium.","method":"Electron microscopy of cell interfaces, FBP17 knockdown/overexpression, fluorescence imaging, Cdc42 epistasis experiments","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined cellular phenotype and epistasis placing Cdc42 upstream, single lab, multiple methods","pmids":["34485872"],"is_preprint":false},{"year":2024,"finding":"FNBP17 interacts with Daam1 formin, co-localizes with it in an actin cytoskeletal complex responsive to Wnt stimulation, and is required for vertebrate gastrulation in Xenopus. FNBP1 and Daam1 function within the same non-canonical Wnt signaling pathway, as suboptimal doses of both synergize to produce severe gastrulation defects. FNBP1 can induce intracellular tubule-like structures and localizes to focal adhesions.","method":"Co-IP/domain interaction mapping, immunofluorescence co-localization, Xenopus loss-of-function (morpholino knockdown), genetic epistasis (synergy between FNBP1 and Daam1)","journal":"Developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP interaction mapping, Xenopus in vivo loss-of-function, epistasis, and localization studies; single lab, multiple orthogonal methods","pmids":["38945423"],"is_preprint":false},{"year":2018,"finding":"FBP17 associates with dynamin and cortactin in invasive breast cancer cells (MDA-MB-231), and its stable knockdown compromises ECM degradation, demonstrating a role in invadopodia-mediated invasion.","method":"Co-immunoprecipitation, stable shRNA knockdown, ECM degradation assay","journal":"Medical oncology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, Co-IP for association and knockdown phenotype without domain dissection or mechanistic depth","pmids":["29651632"],"is_preprint":false},{"year":2024,"finding":"Membrane curvature triggers condensation and activation of N-WASP orchestrated by FBP17: FBP17 senses curvature via its BAR domain and induces hierarchical assembly of FBP17/N-WASP clusters that activate N-WASP in synergy with Cdc42. The stoichiometry of FBP17 to N-WASP within multivalent assemblies is modulated by local curvature radius to tune actin nucleation.","method":"Nanolithography-controlled curvature substrates, reconstituted Cdc42/FBP17/N-WASP system in vitro, quantitative imaging of condensate formation and actin polymerization","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — reconstitution of tri-component system with precise geometric control, quantitative stoichiometry analysis, mechanistic mutagenesis-equivalent domain dissection across curvature range; peer-reviewed publication","pmids":["41484371"],"is_preprint":false},{"year":2023,"finding":"FNBP1 promotes cervical cancer cell survival through constitutive activation of the FAK/PI3K/AKT/mTOR signaling pathway. FNBP1 knockdown reduces cell adhesion, attenuates FAK/PI3K/AKT signaling, and leads to apoptosis. EGF treatment rescues all FNBP1 knockdown effects except the cell adhesion decrease, indicating FNBP1 maintains FAK activity by promoting cell adhesion.","method":"siRNA knockdown, phospho-signaling assays (FAK, PI3K, AKT, mTOR), apoptosis assays, EGF rescue experiments, cell adhesion assays","journal":"Cells","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined signaling pathway readouts and rescue experiment, single lab, multiple orthogonal methods","pmids":["37566043"],"is_preprint":false},{"year":2025,"finding":"FNBP1 interacts with LASP1, upregulates LASP1 protein expression, and subsequently activates the Smad3 signaling pathway to promote glycolysis in glioblastoma cells. FNBP1 mRNA stability is enhanced by RBM15B-mediated m6A modification recognized by IGF2BP2.","method":"Co-IP (FNBP1-LASP1 interaction), m6A modification assays (RBM15B, IGF2BP2), shRNA knockdown, glycolysis assays, xenograft mouse models","journal":"Drug development research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP interaction, m6A modification pathway, in vivo xenograft validation, single lab, multiple orthogonal methods","pmids":["41086050"],"is_preprint":false},{"year":2025,"finding":"FBP17 overexpression induces premature neurite outgrowth in cortical neurons in culture, and either knockdown or overexpression of FBP17 disrupts radial neuron migration and neurite dynamics in vivo in the developing mouse cortex, demonstrating FBP17 is essential for proper cortical neuron migration.","method":"In utero electroporation with Double UP technique for concurrent knockdown/overexpression comparison, in vivo mouse cortex migration assays","journal":"The Journal of neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo loss- and gain-of-function with defined migration phenotype using rigorous Double UP comparison method, single lab","pmids":["40721321"],"is_preprint":false},{"year":2021,"finding":"Sp1 transcription factor drives FNBP1 expression in EMT-type gastric cancer cells; pharmacological inhibition and knockdown of Sp1 reduced FNBP1 promoter activity and transcription. Loss of FNBP1 results in loss of 3D invasive ability and reduced actin dynamics.","method":"Promoter analysis, Sp1 inhibitor/knockdown experiments, FNBP1 knockdown, 3D invasion assay, live imaging of actin dynamics","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — promoter binding, transcriptional regulation, and functional loss-of-function phenotype; single lab, multiple methods","pmids":["34202606"],"is_preprint":false},{"year":2022,"finding":"Wild-type p53 suppresses FBP17 expression; cell lines with mutant p53 express higher FBP17, and stabilization of wild-type p53 reduces FBP17 levels. Double knockdown of p53 and FBP17 showed FBP17 contributes to invasion when p53 loses regulatory control, placing FBP17 downstream of p53 in an invasion-regulatory axis.","method":"p53 stabilization experiments, FBP17 expression measurement, double knockdown epistasis, invasion assays, IHC of breast cancer tissue microarrays","journal":"Carcinogenesis","confidence":"Low","confidence_rationale":"Tier 3 / Weak — epistasis experiment establishes p53-FBP17 regulatory axis but mechanistic detail is limited; IHC component is correlative; single lab","pmids":["35134126"],"is_preprint":false}],"current_model":"FNBP1/FBP17 is an F-BAR domain protein that senses and generates plasma membrane curvature through its F-BAR domain (with curvature-sensing capacity enhanced by an adjacent intrinsically disordered region), recruits WASP/WIP/dynamin-2 to promote actin polymerization at curved membranes, facilitates clathrin-independent (FEME) endocytosis by recruiting SHIP2 and lamellipodin downstream of Cdc42, serves as a mechanosensitive adaptor phosphorylated by c-Abl to couple membrane tension to mDia1-dependent stress fiber remodeling, and activates N-WASP in a curvature radius-dependent manner via hierarchical Cdc42/FBP17/N-WASP condensate assembly; collectively these activities underlie roles in podosome/phagocytic cup formation, invadopodia-driven invasion, cortical neuron migration, non-canonical Wnt signaling during gastrulation, and cell competition."},"narrative":{"mechanistic_narrative":"FNBP1/FBP17 is an F-BAR domain protein that couples plasma membrane curvature sensing and generation to actin cytoskeleton remodeling at sites of membrane deformation [PMID:19155218, PMID:33205024]. Its N-terminal EFC/F-BAR domain binds and deforms membrane while recruiting WASP, WIP, and dynamin-2 to drive localized actin polymerization, an activity required for podosome and phagocytic cup formation in macrophages [PMID:19155218]. Membrane curvature itself triggers hierarchical co-assembly of FBP17/N-WASP clusters that activate N-WASP in synergy with Cdc42, with the FBP17:N-WASP stoichiometry tuned by local curvature radius to set actin nucleation output [PMID:41484371]; an alternatively spliced intrinsically disordered region adjacent to the F-BAR domain provides curvature-sensing capacity exceeding that of the F-BAR domain alone [PMID:33205024]. Acting downstream of GTP-loaded Cdc42, FBP17 primes membranes for fast endophilin-mediated endocytosis by recruiting SHIP2 and lamellipodin to generate phosphatidylinositol-3,4-bisphosphate, with transient assembly and disassembly controlled by RICH1/SH3BP1 GAPs [PMID:30061681]. FBP17 also functions as a mechanosensitive adaptor: c-Abl directly phosphorylates its F-BAR domain under membrane tension, inhibiting membrane bending and releasing FBP17-imposed restraint on mDia1-dependent stress fibers [PMID:31862885]. Through these membrane-and-actin coupling activities, FBP17 supports invadopodia-driven tumor cell invasion [PMID:21421245], cortical neuron migration [PMID:40721321], non-canonical Wnt signaling via Daam1 during Xenopus gastrulation [PMID:38945423], and Cdc42-dependent cell competition [PMID:34485872].","teleology":[{"year":2001,"claim":"Established the earliest physical interactions and domain architecture of FBP17, linking it to membrane trafficking machinery and an actin-regulatory protein family while ruling out direct Rho binding despite a candidate motif.","evidence":"Yeast two-hybrid screen of a human kidney library and domain analysis identifying SNX2 interaction","pmids":["11438682"],"confidence":"Medium","gaps":["Functional consequence of the SNX2 interaction not defined","No demonstration of membrane or actin activity at this stage"]},{"year":2003,"claim":"Identified a TNKS-binding motif in FBP17 connecting it to tankyrase, broadening the candidate interactome beyond trafficking.","evidence":"Yeast two-hybrid plus endogenous co-immunoprecipitation in 293T cells","pmids":["14596906"],"confidence":"Medium","gaps":["Cellular role of FBP17-tankyrase interaction not established","No link to FBP17 membrane or actin functions"]},{"year":2009,"claim":"Defined FBP17's core mechanism: the F-BAR domain simultaneously deforms membrane and recruits WASP/WIP/dynamin-2 to polymerize actin at the same site, explaining its requirement in podosome and phagocytic cup formation.","evidence":"Knockdown/overexpression, domain deletion constructs, and podosome/phagocytic cup assays in macrophages","pmids":["19155218"],"confidence":"High","gaps":["Curvature-sensing versus curvature-generating contributions not separated","Quantitative coupling between membrane deformation and actin output not measured"]},{"year":2009,"claim":"Proposed that FBP17-induced tubulation orients actin polymerization toward endocytic vesicle necks to aid fission, extending its role to clathrin-dependent endocytosis.","evidence":"Fluorescence imaging of actin at FBP17-induced membrane tubules","pmids":["19835875"],"confidence":"Low","gaps":["Single imaging study without mutagenesis or reconstitution; model is interpretive","Direct contribution to fission not demonstrated"]},{"year":2011,"claim":"Showed FBP17 is required for invadopodia formation and invasion, with both the F-BAR (deformation) and SH3 (dynamin-2 recruitment) domains necessary, translating its membrane/actin activity to cancer cell invasion.","evidence":"Knockdown, phalloidin staining, Transwell invasion, and domain-mutant rescue in bladder tumor cells","pmids":["21421245"],"confidence":"Medium","gaps":["Upstream signals driving FBP17 to invadopodia not defined here","Single cancer cell context"]},{"year":2018,"claim":"Placed FBP17 in fast endophilin-mediated endocytosis downstream of Cdc42, recruiting SHIP2 and lamellipodin to generate PI(3,4)P2 and pre-enrich endophilin, with GAP-driven transient assembly.","evidence":"Colocalization screens, Co-IP, lipid phosphatase recruitment assays, live imaging of endophilin foci","pmids":["30061681"],"confidence":"High","gaps":["Selectivity for FEME versus other endocytic routes not fully resolved","How GAP-mediated deactivation timing is set is unclear"]},{"year":2018,"claim":"Associated FBP17 with dynamin and cortactin in breast cancer cells and linked it to ECM degradation, reinforcing an invadopodia role.","evidence":"Co-IP and stable shRNA knockdown with ECM degradation assay in MDA-MB-231 cells","pmids":["29651632"],"confidence":"Low","gaps":["Co-IP for association without domain dissection or reciprocal validation","No mechanistic depth beyond correlation"]},{"year":2019,"claim":"Revealed FBP17 as a mechanosensitive node: c-Abl directly phosphorylates its F-BAR domain under tension, inhibiting membrane bending and de-repressing mDia1-dependent stress fibers, coupling membrane tension to actin adaptation.","evidence":"Knockout cells, osmotic shock, direct c-Abl phosphorylation assays, caveolar rosette and stress fiber analysis, live imaging","pmids":["31862885"],"confidence":"High","gaps":["Phosphosite-resolved structural mechanism of bending inhibition not fully defined","How FBP17 restrains mDia1 prior to phosphorylation unclear"]},{"year":2020,"claim":"Reassigned curvature-sensing capacity to an alternatively spliced IDR adjacent to the F-BAR domain rather than the F-BAR domain itself, refining how FBP17 reads membrane geometry.","evidence":"Nanobar-supported lipid bilayer in vitro curvature assay with domain mutants and live-cell cortical wave imaging","pmids":["33205024"],"confidence":"Medium","gaps":["Physiological splice-isoform distribution not mapped","How IDR sensing integrates with F-BAR deformation in vivo unresolved"]},{"year":2021,"claim":"Extended FBP17 function to tissue-level cell competition, where it acts downstream of Cdc42 to form finger-like protrusions promoting apical elimination of RasV12 cells.","evidence":"Electron microscopy, knockdown/overexpression, fluorescence imaging, and Cdc42 epistasis in mixed epithelia","pmids":["34485872"],"confidence":"Medium","gaps":["Molecular link between protrusions and elimination signaling not defined","Single epithelial competition model"]},{"year":2021,"claim":"Defined Sp1 as a transcriptional driver of FNBP1 in EMT-type gastric cancer, with FNBP1 loss abolishing 3D invasion and reducing actin dynamics.","evidence":"Promoter analysis, Sp1 inhibition/knockdown, FNBP1 knockdown, 3D invasion and actin live imaging","pmids":["34202606"],"confidence":"Medium","gaps":["Direct Sp1 occupancy of the FNBP1 promoter not resolved at base-pair level","Restricted to gastric cancer context"]},{"year":2022,"claim":"Placed FBP17 downstream of p53 in an invasion axis, with wild-type p53 suppressing FBP17 and FBP17 driving invasion when p53 regulation is lost.","evidence":"p53 stabilization, double-knockdown epistasis, invasion assays, and breast cancer tissue IHC","pmids":["35134126"],"confidence":"Low","gaps":["Mechanism of p53-mediated repression not defined; IHC component correlative","Whether repression is direct or indirect unknown"]},{"year":2023,"claim":"Linked FNBP1 to cell survival via FAK/PI3K/AKT/mTOR signaling in cervical cancer, with adhesion maintenance as the upstream node sustaining FAK activity.","evidence":"siRNA knockdown, phospho-signaling and apoptosis assays, EGF rescue, and adhesion assays","pmids":["37566043"],"confidence":"Medium","gaps":["Molecular basis by which FNBP1 promotes adhesion not defined","Connection to its membrane/actin machinery not mechanistically linked"]},{"year":2024,"claim":"Established FNBP1 in non-canonical Wnt signaling, interacting with and synergizing with Daam1 formin to control gastrulation, broadening its actin-regulatory role to vertebrate morphogenesis.","evidence":"Co-IP/domain mapping, immunofluorescence, Xenopus morpholino knockdown, and FNBP1-Daam1 genetic synergy","pmids":["38945423"],"confidence":"Medium","gaps":["Whether the FNBP1-Daam1 actin complex acts through curvature sensing not addressed","Direct downstream effectors in gastrulation undefined"]},{"year":2024,"claim":"Provided the most mechanistic reconstitution to date: membrane curvature triggers condensation of FBP17/N-WASP clusters that activate N-WASP with Cdc42, and curvature radius tunes FBP17:N-WASP stoichiometry to set actin nucleation.","evidence":"Nanolithography-controlled curvature substrates and reconstituted Cdc42/FBP17/N-WASP system with quantitative condensate and actin imaging","pmids":["41484371"],"confidence":"High","gaps":["In vivo validation of stoichiometry tuning across physiological curvatures incomplete","Role of the curvature-sensing IDR within condensates not integrated"]},{"year":2025,"claim":"Demonstrated FBP17 is essential for cortical neuron migration, with both loss and gain of function disrupting radial migration and neurite dynamics in vivo.","evidence":"In utero electroporation with Double UP concurrent knockdown/overexpression in developing mouse cortex","pmids":["40721321"],"confidence":"Medium","gaps":["Molecular effectors of FBP17 in migrating neurons not identified","Whether curvature/actin coupling underlies the migration phenotype not tested"]},{"year":2025,"claim":"Identified an FNBP1-LASP1-Smad3 axis driving glioblastoma glycolysis, with FNBP1 mRNA stabilized by m6A modification, adding a metabolic dimension to FNBP1 biology.","evidence":"Co-IP, m6A assays (RBM15B, IGF2BP2), shRNA knockdown, glycolysis assays, and xenografts","pmids":["41086050"],"confidence":"Medium","gaps":["How a membrane/actin adaptor regulates LASP1 and Smad3 mechanistically unclear","Relationship to FNBP1's curvature/actin functions undefined"]},{"year":null,"claim":"How FNBP1's well-characterized membrane-curvature and actin-coupling machinery mechanistically connects to its reported metabolic (LASP1/Smad3) and survival (FAK/PI3K/AKT) signaling roles remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unifying mechanism linking curvature/actin function to signaling-axis roles","Splice-isoform-specific functions not systematically mapped","Direct structural model of curvature-tuned condensate assembly incomplete"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[2,11,9]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[2,7]},{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[3,7]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,2,11]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,2,3,7]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[2,9,15]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,6]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[8,9,12]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[9,14]}],"complexes":[],"partners":["WASP","WIP","DNM2","CDC42","INPPL1","DAAM1","CTTN","LASP1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96RU3","full_name":"Formin-binding protein 1","aliases":["Formin-binding protein 17","hFBP17"],"length_aa":617,"mass_kda":71.3,"function":"May act as a link between RND2 signaling and regulation of the actin cytoskeleton (By similarity). Required to coordinate membrane tubulation with reorganization of the actin cytoskeleton during the late stage of clathrin-mediated endocytosis. Binds to lipids such as phosphatidylinositol 4,5-bisphosphate and phosphatidylserine and promotes membrane invagination and the formation of tubules. Also enhances actin polymerization via the recruitment of WASL/N-WASP, which in turn activates the Arp2/3 complex. Actin polymerization may promote the fission of membrane tubules to form endocytic vesicles. May be required for the lysosomal retention of FASLG/FASL","subcellular_location":"Cytoplasm; Cytoplasm, cytoskeleton; Cytoplasm, cell cortex; Lysosome; Cytoplasmic vesicle; Cell membrane; Membrane, clathrin-coated pit","url":"https://www.uniprot.org/uniprotkb/Q96RU3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/FNBP1","classification":"Not Classified","n_dependent_lines":5,"n_total_lines":1208,"dependency_fraction":0.0041390728476821195},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000187239","cell_line_id":"CID000528","localizations":[{"compartment":"cell_contact","grade":3},{"compartment":"membrane","grade":3},{"compartment":"cytoplasmic","grade":1}],"interactors":[{"gene":"RAD50","stoichiometry":0.2},{"gene":"H1FX","stoichiometry":0.2},{"gene":"FNBP1L","stoichiometry":0.2},{"gene":"HIST2H2AA3;HIST2H2AC","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000528","total_profiled":1310},"omim":[{"mim_id":"606191","title":"FORMIN-BINDING PROTEIN 1; FNBP1","url":"https://www.omim.org/entry/606191"},{"mim_id":"194521","title":"ZINC FINGER PROTEIN 33A; ZNF33A","url":"https://www.omim.org/entry/194521"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Plasma membrane","reliability":"Supported"},{"location":"Vesicles","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"lymphoid tissue","ntpm":101.9}],"url":"https://www.proteinatlas.org/search/FNBP1"},"hgnc":{"alias_symbol":["FBP17","KIAA0554"],"prev_symbol":[]},"alphafold":{"accession":"Q96RU3","domains":[{"cath_id":"1.20.1270.60","chopping":"4-268","consensus_level":"high","plddt":95.7063,"start":4,"end":268},{"cath_id":"2.30.30.40","chopping":"554-611","consensus_level":"high","plddt":93.2357,"start":554,"end":611},{"cath_id":"1.10.287","chopping":"408-484","consensus_level":"high","plddt":94.0094,"start":408,"end":484}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96RU3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96RU3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96RU3-F1-predicted_aligned_error_v6.png","plddt_mean":78.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=FNBP1","jax_strain_url":"https://www.jax.org/strain/search?query=FNBP1"},"sequence":{"accession":"Q96RU3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96RU3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96RU3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96RU3"}},"corpus_meta":[{"pmid":"30061681","id":"PMC_30061681","title":"FBP17 and CIP4 recruit SHIP2 and lamellipodin to prime the plasma membrane for fast endophilin-mediated endocytosis.","date":"2018","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/30061681","citation_count":78,"is_preprint":false},{"pmid":"11438682","id":"PMC_11438682","title":"The human formin-binding protein 17 (FBP17) interacts with sorting nexin, SNX2, and is an MLL-fusion partner in acute myelogeneous leukemia.","date":"2001","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/11438682","citation_count":71,"is_preprint":false},{"pmid":"19155218","id":"PMC_19155218","title":"FBP17 Mediates a Common Molecular Step in the Formation of Podosomes and Phagocytic Cups in Macrophages.","date":"2009","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19155218","citation_count":58,"is_preprint":false},{"pmid":"31862885","id":"PMC_31862885","title":"An Abl-FBP17 mechanosensing system couples local plasma membrane curvature and stress fiber remodeling during mechanoadaptation.","date":"2019","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/31862885","citation_count":48,"is_preprint":false},{"pmid":"21421245","id":"PMC_21421245","title":"Requirement for FBP17 in invadopodia formation by invasive bladder tumor cells.","date":"2011","source":"The Journal of urology","url":"https://pubmed.ncbi.nlm.nih.gov/21421245","citation_count":43,"is_preprint":false},{"pmid":"33205024","id":"PMC_33205024","title":"Comparative Study of Curvature Sensing Mediated by F-BAR and an Intrinsically Disordered Region of FBP17.","date":"2020","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/33205024","citation_count":23,"is_preprint":false},{"pmid":"29651632","id":"PMC_29651632","title":"High expression of FBP17 in invasive breast cancer cells promotes invadopodia formation.","date":"2018","source":"Medical oncology (Northwood, London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/29651632","citation_count":19,"is_preprint":false},{"pmid":"19835875","id":"PMC_19835875","title":"The direction of actin polymerization for vesicle fission suggested from membranes tubulated by the EFC/F-BAR domain protein FBP17.","date":"2009","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/19835875","citation_count":19,"is_preprint":false},{"pmid":"14596906","id":"PMC_14596906","title":"The formin-binding protein 17, FBP17, binds via a TNKS binding motif to tankyrase, a protein involved in telomere maintenance.","date":"2003","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/14596906","citation_count":16,"is_preprint":false},{"pmid":"34202606","id":"PMC_34202606","title":"Sp1-Induced FNBP1 Drives Rigorous 3D Cell Motility in EMT-Type Gastric Cancer Cells.","date":"2021","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/34202606","citation_count":13,"is_preprint":false},{"pmid":"32665637","id":"PMC_32665637","title":"High formin binding protein 17 (FBP17) expression indicates poor differentiation and invasiveness of ductal carcinomas.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32665637","citation_count":9,"is_preprint":false},{"pmid":"37566043","id":"PMC_37566043","title":"FNBP1 Facilitates Cervical Cancer Cell Survival by the Constitutive Activation of FAK/PI3K/AKT/mTOR Signaling.","date":"2023","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/37566043","citation_count":9,"is_preprint":false},{"pmid":"34485872","id":"PMC_34485872","title":"FBP17-mediated finger-like membrane protrusions in cell competition between normal and RasV12-transformed cells.","date":"2021","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/34485872","citation_count":6,"is_preprint":false},{"pmid":"35201476","id":"PMC_35201476","title":"Silencing long intergenic non-protein coding RNA 00987 inhibits proliferation, migration, and invasion of osteosarcoma cells by sponging miR-376a-5p to regulate FNBP1 expression.","date":"2021","source":"Discover oncology","url":"https://pubmed.ncbi.nlm.nih.gov/35201476","citation_count":6,"is_preprint":false},{"pmid":"26102599","id":"PMC_26102599","title":"Translating Membrane Tension into Cytoskeletal Action by FBP17.","date":"2015","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/26102599","citation_count":6,"is_preprint":false},{"pmid":"35134126","id":"PMC_35134126","title":"Wild-type p53 suppresses formin-binding protein-17 (FBP17) to reduce invasion.","date":"2022","source":"Carcinogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/35134126","citation_count":5,"is_preprint":false},{"pmid":"38712166","id":"PMC_38712166","title":"Membrane curvature catalyzes actin nucleation through nano-scale condensation of N-WASP-FBP17.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/38712166","citation_count":5,"is_preprint":false},{"pmid":"37010470","id":"PMC_37010470","title":"GxcM-Fbp17/RacC-WASP signaling regulates polarized cortex assembly in migrating cells via Arp2/3.","date":"2023","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/37010470","citation_count":4,"is_preprint":false},{"pmid":"38945423","id":"PMC_38945423","title":"Formin Binding Protein 1 (FNBP1) regulates non-canonical Wnt signaling and vertebrate gastrulation.","date":"2024","source":"Developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/38945423","citation_count":3,"is_preprint":false},{"pmid":"39484544","id":"PMC_39484544","title":"F-BAR proteins CIP4 and FBP17 function in cortical neuron radial migration and process outgrowth.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/39484544","citation_count":1,"is_preprint":false},{"pmid":"41484371","id":"PMC_41484371","title":"Membrane curvature initiates Cdc42-FBP17-N-WASP clustering and actin nucleation.","date":"2026","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/41484371","citation_count":1,"is_preprint":false},{"pmid":"40721321","id":"PMC_40721321","title":"F-BAR Proteins CIP4 and FBP17 Function in Cortical Neuron Radial Migration and Process Outgrowth.","date":"2025","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/40721321","citation_count":0,"is_preprint":false},{"pmid":"41086050","id":"PMC_41086050","title":"RBM15B/IGF2BP2-m6A Mediated Upregulation of FNBP1 Promotes the Progression of Glioblastoma by Promoting Smad3-Mediated Glycolysis.","date":"2025","source":"Drug development research","url":"https://pubmed.ncbi.nlm.nih.gov/41086050","citation_count":0,"is_preprint":false},{"pmid":"41717845","id":"PMC_41717845","title":"PM10 Impairs CD56dim NK Cell Cytotoxicity via FNBP1 Suppression to Exacerbate Rheumatoid Arthritis: Insights from Multimodal Multi-Omics.","date":"2026","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/41717845","citation_count":0,"is_preprint":false},{"pmid":"28255515","id":"PMC_28255515","title":"Microarrays-Enabled Hypothesis Generation: The Suspect Role of FNBP-1 in Neuropsychiatric Pathogenesis Associated with HIV and/or HCV Infection.","date":"2016","source":"Journal of AIDS & clinical research","url":"https://pubmed.ncbi.nlm.nih.gov/28255515","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":13211,"output_tokens":4440,"usd":0.053116,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":12407,"output_tokens":5465,"usd":0.09933,"stage2_stop_reason":"end_turn"},"total_usd":0.152446,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"FBP17 and CIP4 prime the plasma membrane for fast endophilin-mediated endocytosis (FEME) by recruiting the 5'-lipid phosphatase SHIP2 and lamellipodin to mediate local production of phosphatidylinositol-3,4-bisphosphate and endophilin pre-enrichment. Membrane-bound GTP-loaded Cdc42 recruits FBP17 and CIP4, which are then locally deactivated by RICH1 and SH3BP1 GAPs, generating transient assembly and disassembly of endophilin spots.\",\n      \"method\": \"Colocalization screens of BAR domain proteins with endophilin, Co-IP, lipid phosphatase recruitment assays, live imaging of endophilin foci dynamics\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal functional assays with multiple orthogonal methods (colocalization, Co-IP, receptor activation, GAP pathway genetics) in a high-quality study\",\n      \"pmids\": [\"30061681\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"FBP17 interacts with sorting nexin SNX2 as identified by yeast two-hybrid screening of a human kidney library, providing a link between the EGF receptor pathway and FBP17. FBP17 contains a C-terminal SH3 domain, an N-terminal region homologous to cdc15 (an actin cytoskeleton regulator in S. pombe), and a consensus Rho-binding motif; however, none of the Rho family proteins tested interacted with FBP17 in yeast two-hybrid assays.\",\n      \"method\": \"Yeast two-hybrid screen, domain analysis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — yeast two-hybrid identification of SNX2 interaction; negative Rho-binding result experimentally established; single lab, single method for positive interaction\",\n      \"pmids\": [\"11438682\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"FBP17 recruits WASP, WIP (WASP-interacting protein), and dynamin-2 to the plasma membrane, and this recruitment is necessary for the formation of podosomes and phagocytic cups in macrophages. The N-terminal EFC/F-BAR domain of FBP17 mediates membrane binding and deformation, enabling simultaneous membrane deformation and actin polymerization at the same sites.\",\n      \"method\": \"FBP17 knockdown/overexpression, fluorescence microscopy, domain deletion constructs, podosome and phagocytic cup formation assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined cellular phenotypes, domain dissection with multiple functional readouts, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"19155218\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"FBP17 is recruited to caveolae to induce formation of caveolar rosettes and buffer plasma membrane tension. c-Abl tyrosine kinase directly phosphorylates the FBP17 F-BAR domain in response to mechanical tension, which inhibits FBP17 membrane-bending activity and releases FBP17-controlled inhibition of mDia1-dependent stress fibers, allowing membrane adaptation to increased mechanical tension.\",\n      \"method\": \"FBP17 knockout cells, osmotic shock assays, phosphorylation assays with c-Abl, live imaging, caveolar rosette quantification, stress fiber analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (KO phenotyping, direct phosphorylation assay, functional rescue, structural domain analysis, live imaging) in a single rigorous study\",\n      \"pmids\": [\"31862885\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"FBP17 localizes to invadopodia in invasive bladder tumor cells, and its knockdown decreases invadopodia formation to 13–14% of control and decreases invasive capacity to 14–16%. Both the EFC/F-BAR domain (membrane deformation) and the SH3 domain (dynamin-2 recruitment) of FBP17 are necessary for invadopodia formation and invasion.\",\n      \"method\": \"FBP17 knockdown, phalloidin staining for invadopodia, Transwell invasion assay, domain mutant constructs\",\n      \"journal\": \"The Journal of urology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined cellular phenotypes and domain dissection, single lab, multiple methods\",\n      \"pmids\": [\"21421245\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"FBP17 binds to tankyrase (TNKS), an ADP-ribose polymerase involved in telomere maintenance and MAPK signaling, via a specific TNKS-binding motif in FBP17. This interaction was identified by yeast two-hybrid assay and confirmed by co-immunoprecipitation of endogenous proteins in 293T cells.\",\n      \"method\": \"Yeast two-hybrid assay, co-immunoprecipitation of endogenous proteins in 293T cells\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — binding confirmed by both yeast two-hybrid and endogenous co-IP, single lab, two complementary methods\",\n      \"pmids\": [\"14596906\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"FBP17-induced membrane tubulation directs actin polymerization toward membrane tubules, suggesting that actin polymerization occurs toward the neck of endocytic vesicles during clathrin-dependent endocytosis to facilitate vesicle fission.\",\n      \"method\": \"Fluorescence imaging of actin dynamics at FBP17-induced membrane tubules\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single imaging study, single lab, no mutagenesis or reconstitution; mechanistic model is largely interpretive\",\n      \"pmids\": [\"19835875\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The F-BAR domain of FBP17 alone displays minimal curvature-sensing activity in vitro. Instead, an alternatively spliced intrinsically disordered region (IDR) adjacent to the F-BAR domain has curvature-sensing ability greatly exceeding that of the F-BAR domain alone. In living cells, presence of the IDR delayed FBP17 recruitment in curvature-coupled cortical waves.\",\n      \"method\": \"Nanobar-supported lipid bilayer system for in vitro curvature sensing, live cell imaging of cortical waves\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — reconstituted in vitro curvature assay with domain mutants validated in live cells, single lab, two orthogonal methods\",\n      \"pmids\": [\"33205024\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"FBP17 accumulates at the interface between RasV12-transformed and normal cells and promotes formation of finger-like membrane protrusions that mediate cell competition. Cdc42 acts upstream of FBP17 in this process. FBP17 plays a positive role in apical elimination of RasV12 cells from the epithelium.\",\n      \"method\": \"Electron microscopy of cell interfaces, FBP17 knockdown/overexpression, fluorescence imaging, Cdc42 epistasis experiments\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined cellular phenotype and epistasis placing Cdc42 upstream, single lab, multiple methods\",\n      \"pmids\": [\"34485872\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"FNBP17 interacts with Daam1 formin, co-localizes with it in an actin cytoskeletal complex responsive to Wnt stimulation, and is required for vertebrate gastrulation in Xenopus. FNBP1 and Daam1 function within the same non-canonical Wnt signaling pathway, as suboptimal doses of both synergize to produce severe gastrulation defects. FNBP1 can induce intracellular tubule-like structures and localizes to focal adhesions.\",\n      \"method\": \"Co-IP/domain interaction mapping, immunofluorescence co-localization, Xenopus loss-of-function (morpholino knockdown), genetic epistasis (synergy between FNBP1 and Daam1)\",\n      \"journal\": \"Developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP interaction mapping, Xenopus in vivo loss-of-function, epistasis, and localization studies; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"38945423\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"FBP17 associates with dynamin and cortactin in invasive breast cancer cells (MDA-MB-231), and its stable knockdown compromises ECM degradation, demonstrating a role in invadopodia-mediated invasion.\",\n      \"method\": \"Co-immunoprecipitation, stable shRNA knockdown, ECM degradation assay\",\n      \"journal\": \"Medical oncology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, Co-IP for association and knockdown phenotype without domain dissection or mechanistic depth\",\n      \"pmids\": [\"29651632\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Membrane curvature triggers condensation and activation of N-WASP orchestrated by FBP17: FBP17 senses curvature via its BAR domain and induces hierarchical assembly of FBP17/N-WASP clusters that activate N-WASP in synergy with Cdc42. The stoichiometry of FBP17 to N-WASP within multivalent assemblies is modulated by local curvature radius to tune actin nucleation.\",\n      \"method\": \"Nanolithography-controlled curvature substrates, reconstituted Cdc42/FBP17/N-WASP system in vitro, quantitative imaging of condensate formation and actin polymerization\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — reconstitution of tri-component system with precise geometric control, quantitative stoichiometry analysis, mechanistic mutagenesis-equivalent domain dissection across curvature range; peer-reviewed publication\",\n      \"pmids\": [\"41484371\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"FNBP1 promotes cervical cancer cell survival through constitutive activation of the FAK/PI3K/AKT/mTOR signaling pathway. FNBP1 knockdown reduces cell adhesion, attenuates FAK/PI3K/AKT signaling, and leads to apoptosis. EGF treatment rescues all FNBP1 knockdown effects except the cell adhesion decrease, indicating FNBP1 maintains FAK activity by promoting cell adhesion.\",\n      \"method\": \"siRNA knockdown, phospho-signaling assays (FAK, PI3K, AKT, mTOR), apoptosis assays, EGF rescue experiments, cell adhesion assays\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined signaling pathway readouts and rescue experiment, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"37566043\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"FNBP1 interacts with LASP1, upregulates LASP1 protein expression, and subsequently activates the Smad3 signaling pathway to promote glycolysis in glioblastoma cells. FNBP1 mRNA stability is enhanced by RBM15B-mediated m6A modification recognized by IGF2BP2.\",\n      \"method\": \"Co-IP (FNBP1-LASP1 interaction), m6A modification assays (RBM15B, IGF2BP2), shRNA knockdown, glycolysis assays, xenograft mouse models\",\n      \"journal\": \"Drug development research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP interaction, m6A modification pathway, in vivo xenograft validation, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"41086050\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"FBP17 overexpression induces premature neurite outgrowth in cortical neurons in culture, and either knockdown or overexpression of FBP17 disrupts radial neuron migration and neurite dynamics in vivo in the developing mouse cortex, demonstrating FBP17 is essential for proper cortical neuron migration.\",\n      \"method\": \"In utero electroporation with Double UP technique for concurrent knockdown/overexpression comparison, in vivo mouse cortex migration assays\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo loss- and gain-of-function with defined migration phenotype using rigorous Double UP comparison method, single lab\",\n      \"pmids\": [\"40721321\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Sp1 transcription factor drives FNBP1 expression in EMT-type gastric cancer cells; pharmacological inhibition and knockdown of Sp1 reduced FNBP1 promoter activity and transcription. Loss of FNBP1 results in loss of 3D invasive ability and reduced actin dynamics.\",\n      \"method\": \"Promoter analysis, Sp1 inhibitor/knockdown experiments, FNBP1 knockdown, 3D invasion assay, live imaging of actin dynamics\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — promoter binding, transcriptional regulation, and functional loss-of-function phenotype; single lab, multiple methods\",\n      \"pmids\": [\"34202606\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Wild-type p53 suppresses FBP17 expression; cell lines with mutant p53 express higher FBP17, and stabilization of wild-type p53 reduces FBP17 levels. Double knockdown of p53 and FBP17 showed FBP17 contributes to invasion when p53 loses regulatory control, placing FBP17 downstream of p53 in an invasion-regulatory axis.\",\n      \"method\": \"p53 stabilization experiments, FBP17 expression measurement, double knockdown epistasis, invasion assays, IHC of breast cancer tissue microarrays\",\n      \"journal\": \"Carcinogenesis\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — epistasis experiment establishes p53-FBP17 regulatory axis but mechanistic detail is limited; IHC component is correlative; single lab\",\n      \"pmids\": [\"35134126\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"FNBP1/FBP17 is an F-BAR domain protein that senses and generates plasma membrane curvature through its F-BAR domain (with curvature-sensing capacity enhanced by an adjacent intrinsically disordered region), recruits WASP/WIP/dynamin-2 to promote actin polymerization at curved membranes, facilitates clathrin-independent (FEME) endocytosis by recruiting SHIP2 and lamellipodin downstream of Cdc42, serves as a mechanosensitive adaptor phosphorylated by c-Abl to couple membrane tension to mDia1-dependent stress fiber remodeling, and activates N-WASP in a curvature radius-dependent manner via hierarchical Cdc42/FBP17/N-WASP condensate assembly; collectively these activities underlie roles in podosome/phagocytic cup formation, invadopodia-driven invasion, cortical neuron migration, non-canonical Wnt signaling during gastrulation, and cell competition.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"FNBP1/FBP17 is an F-BAR domain protein that couples plasma membrane curvature sensing and generation to actin cytoskeleton remodeling at sites of membrane deformation [#2, #7]. Its N-terminal EFC/F-BAR domain binds and deforms membrane while recruiting WASP, WIP, and dynamin-2 to drive localized actin polymerization, an activity required for podosome and phagocytic cup formation in macrophages [#2]. Membrane curvature itself triggers hierarchical co-assembly of FBP17/N-WASP clusters that activate N-WASP in synergy with Cdc42, with the FBP17:N-WASP stoichiometry tuned by local curvature radius to set actin nucleation output [#11]; an alternatively spliced intrinsically disordered region adjacent to the F-BAR domain provides curvature-sensing capacity exceeding that of the F-BAR domain alone [#7]. Acting downstream of GTP-loaded Cdc42, FBP17 primes membranes for fast endophilin-mediated endocytosis by recruiting SHIP2 and lamellipodin to generate phosphatidylinositol-3,4-bisphosphate, with transient assembly and disassembly controlled by RICH1/SH3BP1 GAPs [#0]. FBP17 also functions as a mechanosensitive adaptor: c-Abl directly phosphorylates its F-BAR domain under membrane tension, inhibiting membrane bending and releasing FBP17-imposed restraint on mDia1-dependent stress fibers [#3]. Through these membrane-and-actin coupling activities, FBP17 supports invadopodia-driven tumor cell invasion [#4], cortical neuron migration [#14], non-canonical Wnt signaling via Daam1 during Xenopus gastrulation [#9], and Cdc42-dependent cell competition [#8].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Established the earliest physical interactions and domain architecture of FBP17, linking it to membrane trafficking machinery and an actin-regulatory protein family while ruling out direct Rho binding despite a candidate motif.\",\n      \"evidence\": \"Yeast two-hybrid screen of a human kidney library and domain analysis identifying SNX2 interaction\",\n      \"pmids\": [\"11438682\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Functional consequence of the SNX2 interaction not defined\", \"No demonstration of membrane or actin activity at this stage\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Identified a TNKS-binding motif in FBP17 connecting it to tankyrase, broadening the candidate interactome beyond trafficking.\",\n      \"evidence\": \"Yeast two-hybrid plus endogenous co-immunoprecipitation in 293T cells\",\n      \"pmids\": [\"14596906\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Cellular role of FBP17-tankyrase interaction not established\", \"No link to FBP17 membrane or actin functions\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Defined FBP17's core mechanism: the F-BAR domain simultaneously deforms membrane and recruits WASP/WIP/dynamin-2 to polymerize actin at the same site, explaining its requirement in podosome and phagocytic cup formation.\",\n      \"evidence\": \"Knockdown/overexpression, domain deletion constructs, and podosome/phagocytic cup assays in macrophages\",\n      \"pmids\": [\"19155218\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Curvature-sensing versus curvature-generating contributions not separated\", \"Quantitative coupling between membrane deformation and actin output not measured\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Proposed that FBP17-induced tubulation orients actin polymerization toward endocytic vesicle necks to aid fission, extending its role to clathrin-dependent endocytosis.\",\n      \"evidence\": \"Fluorescence imaging of actin at FBP17-induced membrane tubules\",\n      \"pmids\": [\"19835875\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Single imaging study without mutagenesis or reconstitution; model is interpretive\", \"Direct contribution to fission not demonstrated\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Showed FBP17 is required for invadopodia formation and invasion, with both the F-BAR (deformation) and SH3 (dynamin-2 recruitment) domains necessary, translating its membrane/actin activity to cancer cell invasion.\",\n      \"evidence\": \"Knockdown, phalloidin staining, Transwell invasion, and domain-mutant rescue in bladder tumor cells\",\n      \"pmids\": [\"21421245\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Upstream signals driving FBP17 to invadopodia not defined here\", \"Single cancer cell context\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Placed FBP17 in fast endophilin-mediated endocytosis downstream of Cdc42, recruiting SHIP2 and lamellipodin to generate PI(3,4)P2 and pre-enrich endophilin, with GAP-driven transient assembly.\",\n      \"evidence\": \"Colocalization screens, Co-IP, lipid phosphatase recruitment assays, live imaging of endophilin foci\",\n      \"pmids\": [\"30061681\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Selectivity for FEME versus other endocytic routes not fully resolved\", \"How GAP-mediated deactivation timing is set is unclear\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Associated FBP17 with dynamin and cortactin in breast cancer cells and linked it to ECM degradation, reinforcing an invadopodia role.\",\n      \"evidence\": \"Co-IP and stable shRNA knockdown with ECM degradation assay in MDA-MB-231 cells\",\n      \"pmids\": [\"29651632\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Co-IP for association without domain dissection or reciprocal validation\", \"No mechanistic depth beyond correlation\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Revealed FBP17 as a mechanosensitive node: c-Abl directly phosphorylates its F-BAR domain under tension, inhibiting membrane bending and de-repressing mDia1-dependent stress fibers, coupling membrane tension to actin adaptation.\",\n      \"evidence\": \"Knockout cells, osmotic shock, direct c-Abl phosphorylation assays, caveolar rosette and stress fiber analysis, live imaging\",\n      \"pmids\": [\"31862885\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Phosphosite-resolved structural mechanism of bending inhibition not fully defined\", \"How FBP17 restrains mDia1 prior to phosphorylation unclear\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Reassigned curvature-sensing capacity to an alternatively spliced IDR adjacent to the F-BAR domain rather than the F-BAR domain itself, refining how FBP17 reads membrane geometry.\",\n      \"evidence\": \"Nanobar-supported lipid bilayer in vitro curvature assay with domain mutants and live-cell cortical wave imaging\",\n      \"pmids\": [\"33205024\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Physiological splice-isoform distribution not mapped\", \"How IDR sensing integrates with F-BAR deformation in vivo unresolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Extended FBP17 function to tissue-level cell competition, where it acts downstream of Cdc42 to form finger-like protrusions promoting apical elimination of RasV12 cells.\",\n      \"evidence\": \"Electron microscopy, knockdown/overexpression, fluorescence imaging, and Cdc42 epistasis in mixed epithelia\",\n      \"pmids\": [\"34485872\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Molecular link between protrusions and elimination signaling not defined\", \"Single epithelial competition model\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Defined Sp1 as a transcriptional driver of FNBP1 in EMT-type gastric cancer, with FNBP1 loss abolishing 3D invasion and reducing actin dynamics.\",\n      \"evidence\": \"Promoter analysis, Sp1 inhibition/knockdown, FNBP1 knockdown, 3D invasion and actin live imaging\",\n      \"pmids\": [\"34202606\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Direct Sp1 occupancy of the FNBP1 promoter not resolved at base-pair level\", \"Restricted to gastric cancer context\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Placed FBP17 downstream of p53 in an invasion axis, with wild-type p53 suppressing FBP17 and FBP17 driving invasion when p53 regulation is lost.\",\n      \"evidence\": \"p53 stabilization, double-knockdown epistasis, invasion assays, and breast cancer tissue IHC\",\n      \"pmids\": [\"35134126\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Mechanism of p53-mediated repression not defined; IHC component correlative\", \"Whether repression is direct or indirect unknown\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Linked FNBP1 to cell survival via FAK/PI3K/AKT/mTOR signaling in cervical cancer, with adhesion maintenance as the upstream node sustaining FAK activity.\",\n      \"evidence\": \"siRNA knockdown, phospho-signaling and apoptosis assays, EGF rescue, and adhesion assays\",\n      \"pmids\": [\"37566043\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Molecular basis by which FNBP1 promotes adhesion not defined\", \"Connection to its membrane/actin machinery not mechanistically linked\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Established FNBP1 in non-canonical Wnt signaling, interacting with and synergizing with Daam1 formin to control gastrulation, broadening its actin-regulatory role to vertebrate morphogenesis.\",\n      \"evidence\": \"Co-IP/domain mapping, immunofluorescence, Xenopus morpholino knockdown, and FNBP1-Daam1 genetic synergy\",\n      \"pmids\": [\"38945423\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Whether the FNBP1-Daam1 actin complex acts through curvature sensing not addressed\", \"Direct downstream effectors in gastrulation undefined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Provided the most mechanistic reconstitution to date: membrane curvature triggers condensation of FBP17/N-WASP clusters that activate N-WASP with Cdc42, and curvature radius tunes FBP17:N-WASP stoichiometry to set actin nucleation.\",\n      \"evidence\": \"Nanolithography-controlled curvature substrates and reconstituted Cdc42/FBP17/N-WASP system with quantitative condensate and actin imaging\",\n      \"pmids\": [\"41484371\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"In vivo validation of stoichiometry tuning across physiological curvatures incomplete\", \"Role of the curvature-sensing IDR within condensates not integrated\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrated FBP17 is essential for cortical neuron migration, with both loss and gain of function disrupting radial migration and neurite dynamics in vivo.\",\n      \"evidence\": \"In utero electroporation with Double UP concurrent knockdown/overexpression in developing mouse cortex\",\n      \"pmids\": [\"40721321\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Molecular effectors of FBP17 in migrating neurons not identified\", \"Whether curvature/actin coupling underlies the migration phenotype not tested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identified an FNBP1-LASP1-Smad3 axis driving glioblastoma glycolysis, with FNBP1 mRNA stabilized by m6A modification, adding a metabolic dimension to FNBP1 biology.\",\n      \"evidence\": \"Co-IP, m6A assays (RBM15B, IGF2BP2), shRNA knockdown, glycolysis assays, and xenografts\",\n      \"pmids\": [\"41086050\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"How a membrane/actin adaptor regulates LASP1 and Smad3 mechanistically unclear\", \"Relationship to FNBP1's curvature/actin functions undefined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How FNBP1's well-characterized membrane-curvature and actin-coupling machinery mechanistically connects to its reported metabolic (LASP1/Smad3) and survival (FAK/PI3K/AKT) signaling roles remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No unifying mechanism linking curvature/actin function to signaling-axis roles\", \"Splice-isoform-specific functions not systematically mapped\", \"Direct structural model of curvature-tuned condensate assembly incomplete\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [2, 11, 9]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [2, 7]},\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [3, 7]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 2, 11]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 2, 3, 7]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [2, 9, 15]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8856828\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [8, 9, 12]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [9, 14]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"WASP\", \"WIP\", \"DNM2\", \"CDC42\", \"INPPL1\", \"DAAM1\", \"CTTN\", \"LASP1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}