Affinage

FNBP1

Formin-binding protein 1 · UniProt Q96RU3

Length
617 aa
Mass
71.3 kDa
Annotated
2026-06-09
25 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2001 Medium

    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

    PMID:11438682

    Open questions at the time
    • Functional consequence of the SNX2 interaction not defined
    • No demonstration of membrane or actin activity at this stage
  2. 2003 Medium

    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

    PMID:14596906

    Open questions at the time
    • Cellular role of FBP17-tankyrase interaction not established
    • No link to FBP17 membrane or actin functions
  3. 2009 High

    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

    PMID:19155218

    Open questions at the time
    • Curvature-sensing versus curvature-generating contributions not separated
    • Quantitative coupling between membrane deformation and actin output not measured
  4. 2009 Low

    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

    PMID:19835875

    Open questions at the time
    • Single imaging study without mutagenesis or reconstitution; model is interpretive
    • Direct contribution to fission not demonstrated
  5. 2011 Medium

    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

    PMID:21421245

    Open questions at the time
    • Upstream signals driving FBP17 to invadopodia not defined here
    • Single cancer cell context
  6. 2018 High

    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

    PMID:30061681

    Open questions at the time
    • Selectivity for FEME versus other endocytic routes not fully resolved
    • How GAP-mediated deactivation timing is set is unclear
  7. 2018 Low

    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

    PMID:29651632

    Open questions at the time
    • Co-IP for association without domain dissection or reciprocal validation
    • No mechanistic depth beyond correlation
  8. 2019 High

    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

    PMID:31862885

    Open questions at the time
    • Phosphosite-resolved structural mechanism of bending inhibition not fully defined
    • How FBP17 restrains mDia1 prior to phosphorylation unclear
  9. 2020 Medium

    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

    PMID:33205024

    Open questions at the time
    • Physiological splice-isoform distribution not mapped
    • How IDR sensing integrates with F-BAR deformation in vivo unresolved
  10. 2021 Medium

    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

    PMID:34485872

    Open questions at the time
    • Molecular link between protrusions and elimination signaling not defined
    • Single epithelial competition model
  11. 2021 Medium

    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

    PMID:34202606

    Open questions at the time
    • Direct Sp1 occupancy of the FNBP1 promoter not resolved at base-pair level
    • Restricted to gastric cancer context
  12. 2022 Low

    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

    PMID:35134126

    Open questions at the time
    • Mechanism of p53-mediated repression not defined; IHC component correlative
    • Whether repression is direct or indirect unknown
  13. 2023 Medium

    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

    PMID:37566043

    Open questions at the time
    • Molecular basis by which FNBP1 promotes adhesion not defined
    • Connection to its membrane/actin machinery not mechanistically linked
  14. 2024 Medium

    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

    PMID:38945423

    Open questions at the time
    • Whether the FNBP1-Daam1 actin complex acts through curvature sensing not addressed
    • Direct downstream effectors in gastrulation undefined
  15. 2024 High

    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

    PMID:41484371

    Open questions at the time
    • In vivo validation of stoichiometry tuning across physiological curvatures incomplete
    • Role of the curvature-sensing IDR within condensates not integrated
  16. 2025 Medium

    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

    PMID:40721321

    Open questions at the time
    • Molecular effectors of FBP17 in migrating neurons not identified
    • Whether curvature/actin coupling underlies the migration phenotype not tested
  17. 2025 Medium

    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

    PMID:41086050

    Open questions at the time
    • How a membrane/actin adaptor regulates LASP1 and Smad3 mechanistically unclear
    • Relationship to FNBP1's curvature/actin functions undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • 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.
  • 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

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 3 GO:0008289 lipid binding 2 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005856 cytoskeleton 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1266738 Developmental Biology 2 R-HSA-5653656 Vesicle-mediated transport 2

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 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. Colocalization screens of BAR domain proteins with endophilin, Co-IP, lipid phosphatase recruitment assays, live imaging of endophilin foci dynamics Nature cell biology High 30061681
2001 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. Yeast two-hybrid screen, domain analysis Proceedings of the National Academy of Sciences of the United States of America Medium 11438682
2009 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. FBP17 knockdown/overexpression, fluorescence microscopy, domain deletion constructs, podosome and phagocytic cup formation assays The Journal of biological chemistry High 19155218
2019 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. FBP17 knockout cells, osmotic shock assays, phosphorylation assays with c-Abl, live imaging, caveolar rosette quantification, stress fiber analysis Nature communications High 31862885
2011 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. FBP17 knockdown, phalloidin staining for invadopodia, Transwell invasion assay, domain mutant constructs The Journal of urology Medium 21421245
2003 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. Yeast two-hybrid assay, co-immunoprecipitation of endogenous proteins in 293T cells FEBS letters Medium 14596906
2009 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. Fluorescence imaging of actin dynamics at FBP17-induced membrane tubules FEBS letters Low 19835875
2020 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. Nanobar-supported lipid bilayer system for in vitro curvature sensing, live cell imaging of cortical waves iScience Medium 33205024
2021 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. Electron microscopy of cell interfaces, FBP17 knockdown/overexpression, fluorescence imaging, Cdc42 epistasis experiments iScience Medium 34485872
2024 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. Co-IP/domain interaction mapping, immunofluorescence co-localization, Xenopus loss-of-function (morpholino knockdown), genetic epistasis (synergy between FNBP1 and Daam1) Developmental biology Medium 38945423
2018 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. Co-immunoprecipitation, stable shRNA knockdown, ECM degradation assay Medical oncology Low 29651632
2024 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. Nanolithography-controlled curvature substrates, reconstituted Cdc42/FBP17/N-WASP system in vitro, quantitative imaging of condensate formation and actin polymerization The EMBO journal High 41484371
2023 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. siRNA knockdown, phospho-signaling assays (FAK, PI3K, AKT, mTOR), apoptosis assays, EGF rescue experiments, cell adhesion assays Cells Medium 37566043
2025 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. Co-IP (FNBP1-LASP1 interaction), m6A modification assays (RBM15B, IGF2BP2), shRNA knockdown, glycolysis assays, xenograft mouse models Drug development research Medium 41086050
2025 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. In utero electroporation with Double UP technique for concurrent knockdown/overexpression comparison, in vivo mouse cortex migration assays The Journal of neuroscience Medium 40721321
2021 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. Promoter analysis, Sp1 inhibitor/knockdown experiments, FNBP1 knockdown, 3D invasion assay, live imaging of actin dynamics International journal of molecular sciences Medium 34202606
2022 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. p53 stabilization experiments, FBP17 expression measurement, double knockdown epistasis, invasion assays, IHC of breast cancer tissue microarrays Carcinogenesis Low 35134126

Source papers

Stage 0 corpus · 25 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 FBP17 and CIP4 recruit SHIP2 and lamellipodin to prime the plasma membrane for fast endophilin-mediated endocytosis. Nature cell biology 78 30061681
2001 The human formin-binding protein 17 (FBP17) interacts with sorting nexin, SNX2, and is an MLL-fusion partner in acute myelogeneous leukemia. Proceedings of the National Academy of Sciences of the United States of America 71 11438682
2009 FBP17 Mediates a Common Molecular Step in the Formation of Podosomes and Phagocytic Cups in Macrophages. The Journal of biological chemistry 58 19155218
2019 An Abl-FBP17 mechanosensing system couples local plasma membrane curvature and stress fiber remodeling during mechanoadaptation. Nature communications 48 31862885
2011 Requirement for FBP17 in invadopodia formation by invasive bladder tumor cells. The Journal of urology 43 21421245
2020 Comparative Study of Curvature Sensing Mediated by F-BAR and an Intrinsically Disordered Region of FBP17. iScience 23 33205024
2018 High expression of FBP17 in invasive breast cancer cells promotes invadopodia formation. Medical oncology (Northwood, London, England) 19 29651632
2009 The direction of actin polymerization for vesicle fission suggested from membranes tubulated by the EFC/F-BAR domain protein FBP17. FEBS letters 19 19835875
2003 The formin-binding protein 17, FBP17, binds via a TNKS binding motif to tankyrase, a protein involved in telomere maintenance. FEBS letters 16 14596906
2021 Sp1-Induced FNBP1 Drives Rigorous 3D Cell Motility in EMT-Type Gastric Cancer Cells. International journal of molecular sciences 13 34202606
2023 FNBP1 Facilitates Cervical Cancer Cell Survival by the Constitutive Activation of FAK/PI3K/AKT/mTOR Signaling. Cells 9 37566043
2020 High formin binding protein 17 (FBP17) expression indicates poor differentiation and invasiveness of ductal carcinomas. Scientific reports 9 32665637
2021 FBP17-mediated finger-like membrane protrusions in cell competition between normal and RasV12-transformed cells. iScience 6 34485872
2021 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. Discover oncology 6 35201476
2015 Translating Membrane Tension into Cytoskeletal Action by FBP17. Developmental cell 6 26102599
2024 Membrane curvature catalyzes actin nucleation through nano-scale condensation of N-WASP-FBP17. bioRxiv : the preprint server for biology 5 38712166
2022 Wild-type p53 suppresses formin-binding protein-17 (FBP17) to reduce invasion. Carcinogenesis 5 35134126
2023 GxcM-Fbp17/RacC-WASP signaling regulates polarized cortex assembly in migrating cells via Arp2/3. The Journal of cell biology 4 37010470
2024 Formin Binding Protein 1 (FNBP1) regulates non-canonical Wnt signaling and vertebrate gastrulation. Developmental biology 3 38945423
2026 Membrane curvature initiates Cdc42-FBP17-N-WASP clustering and actin nucleation. The EMBO journal 1 41484371
2024 F-BAR proteins CIP4 and FBP17 function in cortical neuron radial migration and process outgrowth. bioRxiv : the preprint server for biology 1 39484544
2026 PM10 Impairs CD56dim NK Cell Cytotoxicity via FNBP1 Suppression to Exacerbate Rheumatoid Arthritis: Insights from Multimodal Multi-Omics. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41717845
2025 F-BAR Proteins CIP4 and FBP17 Function in Cortical Neuron Radial Migration and Process Outgrowth. The Journal of neuroscience : the official journal of the Society for Neuroscience 0 40721321
2025 RBM15B/IGF2BP2-m6A Mediated Upregulation of FNBP1 Promotes the Progression of Glioblastoma by Promoting Smad3-Mediated Glycolysis. Drug development research 0 41086050
2016 Microarrays-Enabled Hypothesis Generation: The Suspect Role of FNBP-1 in Neuropsychiatric Pathogenesis Associated with HIV and/or HCV Infection. Journal of AIDS & clinical research 0 28255515

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