Affinage

FBF1

Fas-binding factor 1 · UniProt Q8TES7

Length
1133 aa
Mass
125.4 kDa
Annotated
2026-06-09
16 papers in source corpus 8 papers cited in narrative 8 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/6 claims corpus-supported (67%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FBF1 is a transition fibre and centrosomal protein that governs ciliary import and centriole/centrosome dynamics (PMID:24231678, PMID:30318703). At the ciliary base, FBF1 (and its C. elegans homologue DYF-19) localizes to transition fibres and is required for import of assembled IFT particles into the cilium, acting through a direct interaction with the IFT-B component IFT54 (DYF-11) (PMID:24231678); its recruitment to transition fibres depends on a complex with TALPID3 and ANKRD26, which sets ciliary gating (PMID:32366837). Beyond the cilium, FBF1 promotes centriole duplication by recruiting the cartwheel protein HsSAS-6 and drives mitotic centrosome separation by recruiting Plk1 in a manner requiring phosphorylation at S348 (PMID:30318703), and it acts at spindle poles during mouse oocyte meiosis, where its loss causes spindle assembly and chromosome alignment defects coupled to reduced/mislocalized Plk1 and BubR1 activation (PMID:33561696). The conserved orthologue Twitchy is required for both sensory cilia and cytosolic sperm flagella in Drosophila (PMID:34357392). In breast cancer cells, FBF1 binds PI3K to activate AKT phosphorylation, which engages SOX2 and elevates SOX2/OCT4 activity to sustain cancer stem cell-like properties (PMID:39988656). Structural analysis of the C. elegans FBF-1 shows a C-terminal PUF-interacting motif that contacts its own RNA-binding domain, though FBF-1 itself is not measurably autoinhibited under tested conditions (PMID:40769718).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2000 Low

    The first attempt to assign FBF1 a molecular partner asked what receptor pathway it might serve, placing it at the CD95/FAS cytosolic domain.

    Evidence yeast two-hybrid screen against the murine CD95 cytosolic domain

    PMID:10978533

    Open questions at the time
    • single yeast two-hybrid without biochemical confirmation
    • no functional consequence of the FAS interaction established
    • later work did not return to the apoptosis/FAS link
  2. 2013 High

    Established FBF1's principal cellular role by showing it is a transition fibre protein that gates ciliary entry of IFT particles via direct IFT54 binding, answering how assembled IFT complexes cross the ciliary base.

    Evidence whole-genome ciliogenesis screen, co-localization, direct interaction assays and loss-of-function in C. elegans and mammalian cells

    PMID:24231678

    Open questions at the time
    • mechanism of how the IFT54 interaction physically licenses entry not resolved
    • stoichiometry/structure of the FBF1-IFT54 interface unknown
  3. 2018 Medium

    Extended FBF1 beyond the cilium into centriole biogenesis and mitosis, identifying it as a recruiter of HsSAS-6 for duplication and of Plk1 for centrosome separation in a phospho-dependent manner.

    Evidence monospecific antibodies, siRNA knockdown with rescue, S348 phosphosite analysis and localization in mammalian cells

    PMID:30318703

    Open questions at the time
    • kinase responsible for S348 phosphorylation not identified
    • single lab, two orthogonal readouts only
    • direct vs. indirect recruitment of HsSAS-6/Plk1 not biochemically distinguished
  4. 2020 High

    Answered how FBF1 itself is delivered to transition fibres, defining a TALPID3-ANKRD26 complex required for its localization and thus for cilia gating.

    Evidence C. elegans forward genetic screen, reciprocal co-immunoprecipitation, siRNA and immunofluorescence in mammalian cells

    PMID:32366837

    Open questions at the time
    • molecular basis of the TALPID3/ANKRD26 recruitment interface unknown
    • whether the complex regulates FBF1 function beyond localization unresolved
  5. 2021 Medium

    Tested whether FBF1's centrosomal role extends to meiosis, showing it operates at oocyte spindle poles upstream of Plk1 and the spindle assembly checkpoint.

    Evidence immunofluorescence, siRNA microinjection, western blot and microtubule drug treatment in mouse oocytes

    PMID:33561696

    Open questions at the time
    • direct vs. indirect control of Plk1 in oocytes not separated
    • single lab
    • mechanism linking FBF1 loss to BubR1 activation not defined
  6. 2021 Medium

    Confirmed conservation and physiological breadth of FBF1 function by showing the Drosophila orthologue is needed for both compartmentalized cilia and cytosolic sperm flagella.

    Evidence loss-of-function mutants and germline-specific RNAi with sperm motility and axoneme analysis in Drosophila

    PMID:34357392

    Open questions at the time
    • molecular role in cytosolic flagellogenesis distinct from transition-fibre gating not defined
    • single organism/lab
  7. 2025 Medium

    Identified a disease-relevant signaling function, showing FBF1 binds PI3K to drive an AKT/SOX2/OCT4 axis sustaining breast cancer stem cells.

    Evidence co-immunoprecipitation, RNA-seq, siRNA/overexpression, PI3K inhibition and xenograft models

    PMID:39988656

    Open questions at the time
    • direct FBF1-PI3K interface not structurally mapped
    • relationship of this cytoplasmic signaling role to its centrosomal/ciliary functions unclear
    • single lab
  8. 2025 High

    Addressed the structural logic of the C. elegans FBF-1 C-terminus, revealing an autoinhibition-capable PIM-RNA-binding-domain contact that, unlike FBF-2, does not measurably autoinhibit FBF-1 RNA binding.

    Evidence crystal structure, RNA-binding affinity assays, chimeric proteins and mutagenesis

    PMID:40769718

    Open questions at the time
    • functional consequence of the non-autoinhibited state in vivo unknown
    • relationship between this PUF RNA-binding activity and the centrosomal/ciliary FBF1 role not reconciled

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FBF1's distinct activities — transition-fibre IFT gating, centriole/spindle regulation, RNA binding, and PI3K-AKT signaling — are integrated within one protein, and whether they reflect tissue-specific or context-specific deployment, remains unresolved.
  • no unifying structural/domain map linking the ciliary, centrosomal, RNA-binding and signaling functions
  • no human disease causation established in the corpus
  • C. elegans PUF RNA-binding role not connected to mammalian FBF1 centrosomal function

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2 GO:0003723 RNA binding 1
Localization
GO:0005815 microtubule organizing center 2 GO:0005929 cilium 2 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 2 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
ANKRD26FASHSSAS-6IFT54PIK3PLK1TALPID3
Complex memberships
FBF1-TALPID3-ANKRD26 complex

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 Human FBF1 is a transition fibre protein required for the ciliary import of assembled IFT (intraflagellar transport) particles at the ciliary base. Its C. elegans homologue DYF-19 localizes specifically to transition fibres and directly interacts with the IFT-B component DYF-11/IFT54, and is required for transit of assembled IFT particles through the ciliary base. Whole-genome ciliogenesis screen, co-localization, direct protein interaction assays, loss-of-function analysis in C. elegans and mammalian cells Nature communications High 24231678
2020 TALPID3 and ANKRD26 form a complex with FBF1 and are required for the recruitment of FBF1 to transition fibres, thereby regulating cilia gating. Co-depletion of TALPID3 and ANKRD26 specifically impairs FBF1 localization to transition fibres in both C. elegans (TALP-3/ANKR-26/DYF-19) and mammalian cells. Forward genetic screen in C. elegans, co-immunoprecipitation, siRNA knockdown, immunofluorescence localization in mammalian cells Nature communications High 32366837
2018 FBF1 (Albatross) mediates centriole duplication by recruiting HsSAS-6 (a cartwheel protein) to centrioles. FBF1 also participates in centrosome separation during mitosis by recruiting Plk1; this function requires phosphorylation of FBF1 at residue S348. Monospecific antibodies, full-length constructs, siRNA knockdown, rescue experiments, localization analysis Genes to cells : devoted to molecular & cellular mechanisms Medium 30318703
2021 Fbf1 localizes to spindle poles and around microtubules in mouse oocytes. Knockdown of Fbf1 by siRNA causes severe spindle assembly defects, chromosome misalignment, reduced microtubule aggregation, failure of first polar body extrusion, reduced Plk1 expression and its mis-localization at spindle poles, and activation of spindle assembly checkpoint component BubR1. Immunofluorescence, siRNA microinjection, western blot, taxol/nocodazole treatment in mouse oocytes Theriogenology Medium 33561696
2000 Human/mouse FBF1 (Fas binding factor 1) binds to the cytosolic domain of the CD95/APO-1/FAS receptor. The protein is ~130 kDa, is cytoplasmic, contains a C-terminal leucine heptad repeat, and shows sequence similarity to trichohyalin and plectin. Yeast two-hybrid assay with cytosolic domain of murine CD95 Biochimica et biophysica acta Low 10978533
2025 FBF1 binds PI3K and activates PI3K-AKT phosphorylation; the activated p-AKT then interacts with SOX2, elevating SOX2 and OCT4 activity to maintain cancer stem cell-like properties in breast cancer cells. Co-immunoprecipitation, RNA sequencing, siRNA knockdown, overexpression, xenograft model, PI3K inhibitor treatment Stem cell research & therapy Medium 39988656
2021 Twitchy, the Drosophila orthologue of FBF1/dyf-19, is required for the function of both compartmentalised sensory cilia and sperm flagella formed within the cytosol. Loss-of-function results in adult lethality and uncoordinated locomotion; germline-specific RNAi knockdown produces coordinated but infertile adults with impaired motile sperm production despite normal axoneme elongation and polyglycylation. Loss-of-function mutants, RNAi germline-specific knockdown, sperm motility and axoneme analysis in Drosophila Biology open Medium 34357392
2025 A crystal structure of FBF-1 showed that a PUF-interacting motif (PIM) in the FBF-1 C-terminal tail binds to its own RNA-binding domain, analogous to FBF-2 autoinhibition. However, unlike FBF-2, the FBF-1 CT does not measurably autoinhibit RNA-binding affinity under the tested conditions. Chimeric protein experiments revealed that the FBF-2 CT can autoinhibit FBF-1 RNA binding, and substitution of the FBF-1 PIM with the FBF-2 PIM diminished FBF-2 autoinhibition. Crystal structure, RNA-binding affinity assays, chimeric protein construction, mutagenesis RNA (New York, N.Y.) High 40769718

Source papers

Stage 0 corpus · 16 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 FBF-1 and FBF-2 regulate the size of the mitotic region in the C. elegans germline. Developmental cell 149 15525531
2005 Binding specificity and mRNA targets of a C. elegans PUF protein, FBF-1. RNA (New York, N.Y.) 117 15769874
2013 Transition fibre protein FBF1 is required for the ciliary entry of assembled intraflagellar transport complexes. Nature communications 98 24231678
2005 Redundant control of the Caenorhabditis elegans sperm/oocyte switch by PUF-8 and FBF-1, two distinct PUF RNA-binding proteins. Proceedings of the National Academy of Sciences of the United States of America 61 16037210
2010 The Puf RNA-binding proteins FBF-1 and FBF-2 inhibit the expression of synaptonemal complex proteins in germline stem cells. Development (Cambridge, England) 50 20431119
2020 TALPID3 and ANKRD26 selectively orchestrate FBF1 localization and cilia gating. Nature communications 23 32366837
2020 Antagonistic control of Caenorhabditis elegans germline stem cell proliferation and differentiation by PUF proteins FBF-1 and FBF-2. eLife 17 32804074
2000 A novel protein (Fbf-1) that binds to CD95/APO-1/FAS and shows sequence similarity to trichohyalin and plectin. Biochimica et biophysica acta 13 10978533
2019 The Associations of PMF1, ICAM1, AGT, TRIM65, FBF1, and ACOX1 Variants With Leukoaraiosis in Chinese Population. Frontiers in genetics 7 31396257
2021 Fbf1 regulates mouse oocyte meiosis by influencing Plk1. Theriogenology 6 33561696
2018 Albatross/FBF1 contributes to both centriole duplication and centrosome separation. Genes to cells : devoted to molecular & cellular mechanisms 6 30318703
2025 FBF1 maintains stem cell-like properties in breast cancer via PI3K/AKT/SOX2 axis. Stem cell research & therapy 3 39988656
2021 Twitchy, the Drosophila orthologue of the ciliary gating protein FBF1/dyf-19, is required for coordinated locomotion and male fertility. Biology open 3 34357392
2024 COP9 signalosome component CSN-5 stabilizes PUF proteins FBF-1 and FBF-2 in Caenorhabditis elegans germline stem and progenitor cells. Genetics 1 38427913
2025 Caenorhabditis elegans FBF-1 and FBF-2 C-terminal intrinsically disordered regions differentially regulate RNA-binding affinity. RNA (New York, N.Y.) 0 40769718
2024 Exercise Alters FBF1-Regulated Novel-miRNA-1135 Associated with Hydrolethalus Syndrome 1 in Rheumatoid Arthritis: A Preliminary Study. MicroRNA (Shariqah, United Arab Emirates) 0 38963098

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