Affinage

FSCB

Fibrous sheath CABYR-binding protein · UniProt Q5H9T9

Length
825 aa
Mass
88.0 kDa
Annotated
2026-06-09
10 papers in source corpus 4 papers cited in narrative 4 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FSCB (fibrous sheath CABYR binding protein) is a testis- and sperm-specific calcium-binding protein that operates in a PKA-driven signaling module controlling sperm flagellar motility during capacitation (PMID:17855365). It is first expressed at step 11 of spermatogenesis in elongating spermatids and localizes ultrastructurally to a cortical layer at the surface of the ribs and longitudinal columns of the fibrous sheath principal piece, where it binds the calcium-binding protein CABYR (PMID:17855365). During capacitation, FSCB is rapidly phosphorylated on both tyrosine and Ser/Thr residues in a strictly PKA-dependent manner, with the extent of phosphorylation tracking PKA activity and sperm motility (PMID:17855365, PMID:21871179). Phosphorylated FSCB binds ROPN1 and ROPN1L with markedly increased affinity and suppresses their SUMOylation, an effect that recapitulates the pro-motility consequence of FSCB phosphorylation; reciprocally, ROPN1 is required for normal FSCB incorporation/stability in the fibrous sheath and ROPN1L is required for FSCB phosphorylation (PMID:23303679, PMID:27398160). Beyond this PKA–FSCB–ROPN1/ROPN1L motility axis, no further mechanistic detail has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2007 High

    Established FSCB as a distinct sperm structural-signaling protein by defining its identity, binding partner, post-translational regulation, and precise location in the flagellum.

    Evidence Co-IP/binding assay for CABYR interaction, in vitro PKA phosphorylation with native phosphosite mapping, calcium overlay, and immunofluorescence/EM localization in mouse sperm

    PMID:17855365

    Open questions at the time
    • Functional consequence of CABYR binding not tested
    • Role of calcium binding not defined
    • No loss-of-function phenotype established
  2. 2011 Medium

    Connected FSCB phosphorylation to the capacitation program, showing it is an early PKA-dependent event whose magnitude correlates with motility.

    Evidence Reciprocal phospho-specific immunoprecipitation, pharmacological PKA manipulation (db-cAMP, H-89), and time-course during in vitro capacitation in mouse sperm

    PMID:21871179

    Open questions at the time
    • Correlation with motility not shown to be causal
    • Kinase acting on tyrosine residues not identified
    • No in vitro reconstitution
  3. 2013 Medium

    Placed FSCB within a reciprocal dependency with ROPN1/ROPN1L, showing ROPN1 controls FSCB incorporation/stability and ROPN1L controls FSCB phosphorylation.

    Evidence ROPN1, ROPN1L, and double knockout mouse models with Western blotting for FSCB protein levels and PKA phosphorylation substrates

    PMID:23303679

    Open questions at the time
    • Mechanism of ROPN1-dependent FSCB incorporation not resolved
    • Direct vs indirect effect on phosphorylation not distinguished
    • Single lab
  4. 2016 Medium

    Defined the downstream output of FSCB phosphorylation: phospho-dependent high-affinity binding to ROPN1/ROPN1L that suppresses their SUMOylation and drives motility.

    Evidence Immunoprecipitation comparing phospho vs non-phospho FSCB binding, SUMOylation assays, and motility analysis showing SUMOylation suppression mimics FSCB phosphorylation

    PMID:27398160

    Open questions at the time
    • SUMO ligase/site on ROPN1/ROPN1L not mapped
    • No in vitro reconstitution of the binding-SUMOylation link
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FSCB integrates its calcium binding and CABYR interaction with the PKA-ROPN1/ROPN1L SUMOylation axis, and whether FSCB loss itself impairs fertility, remains unresolved.
  • No FSCB knockout phenotype reported
  • Functional role of calcium binding unknown
  • Structural basis of phospho-dependent ROPN1 binding undetermined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 1
Localization
GO:0005856 cytoskeleton 1
Pathway
R-HSA-1474165 Reproduction 2
Partners
CABYRROPN1ROPN1L
Complex memberships
fibrous sheath

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 FSCB (fibrous sheath CABYR binding protein) is a testis- and sperm-specific protein that binds CABYR (a calcium-binding protein tyrosine-phosphorylated during capacitation), as demonstrated by co-immunoprecipitation/binding assays. FSCB is phosphorylated by protein kinase A (PKA) in vitro and at native phosphorylation sites in mouse sperm. FSCB itself is a calcium-binding protein as shown by calcium overlay assay. It localizes ultrastructurally to a cortical layer at the surface of the ribs and longitudinal columns of the fibrous sheath principal piece in mouse sperm flagella, and is first expressed at step 11 of spermatogenesis in elongating spermatids. Co-immunoprecipitation/binding assay (CABYR interaction), in vitro PKA phosphorylation assay with native phosphorylation site mapping, calcium overlay assay, immunofluorescence and electron microscopy localization The Journal of biological chemistry High 17855365
2011 FSCB undergoes both tyrosine and Ser/Thr phosphorylation during mouse spermatozoa capacitation, detectable as early as 1 min after capacitation onset and increasing over 60 min. Phosphorylation is induced by the PKA agonist db-cAMP and blocked by the PKA antagonist H-89, confirming PKA-dependence. The extent of FSCB phosphorylation correlates with PKA activity and sperm motility characteristics. Immunoprecipitation with anti-phosphotyrosine and anti-phosphoSer/Thr antibodies, pharmacological manipulation (db-cAMP, H-89), time-course analysis during in vitro capacitation BMB reports Medium 21871179
2013 FSCB protein levels are reduced in sperm from ROPN1 knockout (RKO) mice, indicating that ROPN1 is required for normal FSCB incorporation or stability in the fibrous sheath. Separately, sperm from ROPN1L knockout (RLKO) mice show reduced PKA phosphorylation of a 270-kDa protein identified as FSCB, linking ROPN1L to FSCB phosphorylation signaling. Genetic knockout mouse models (RKO, RLKO, DKO), Western blotting for FSCB protein levels and PKA phosphorylation substrates Biology of reproduction Medium 23303679
2016 Phosphorylated FSCB suppresses SUMOylation of ROPN1 and ROPN1L during mouse spermatozoa capacitation. Immunoprecipitation showed that phosphorylated FSCB has significantly higher binding affinity to ROPN1/ROPN1L than non-phosphorylated FSCB. Suppression of ROPN1/ROPN1L SUMOylation mimicked the pro-motility effects of FSCB phosphorylation. Immunoprecipitation assay comparing phosphorylated vs. non-phosphorylated FSCB binding to ROPN1/ROPN1L; SUMOylation assays; sperm motility analysis American journal of translational research Medium 27398160

Source papers

Stage 0 corpus · 10 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Loss of R2D2 proteins ROPN1 and ROPN1L causes defects in murine sperm motility, phosphorylation, and fibrous sheath integrity. Biology of reproduction 83 23303679
2011 High-throughput genotyping in osteosarcoma identifies multiple mutations in phosphoinositide-3-kinase and other oncogenes. Cancer 58 22006429
2007 FSCB, a novel protein kinase A-phosphorylated calcium-binding protein, is a CABYR-binding partner involved in late steps of fibrous sheath biogenesis. The Journal of biological chemistry 38 17855365
2015 Production of the antibiotic FR-008/candicidin in Streptomyces sp. FR-008 is co-regulated by two regulators, FscRI and FscRIV, from different transcription factor families. Microbiology (Reading, England) 26 25575546
2016 FSCB phosphorylation regulates mouse spermatozoa capacitation through suppressing SUMOylation of ROPN1/ROPN1L. American journal of translational research 16 27398160
2011 FSCB phosphorylation in mouse spermatozoa capacitation. BMB reports 11 21871179
2016 Variation in PTCHD2, CRISP3, NAP1L4, FSCB, and AP3B2 associated with spherical equivalent. Molecular vision 9 27440996
2022 Tomato spotted wilt orthotospovirus shifts sex ratio toward males in the western flower thrips, Frankliniella occidentalis, by down-regulating a FSCB-like gene. Pest management science 5 36054039
2024 An updated reference genome sequence and annotation reveals gene losses and gains underlying naked mole-rat biology. bioRxiv : the preprint server for biology 4 39651266
2024 Genomic Regions Associated with Growth and Reproduction Traits in Pink-Eyed White Mink. Genes 1 39336733

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