Affinage

FKBP10

Peptidyl-prolyl cis-trans isomerase FKBP10 · UniProt Q96AY3

Length
582 aa
Mass
64.2 kDa
Annotated
2026-06-09
63 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FKBP10 (FKBP65) is an ER-luminal, multidomain peptidyl-prolyl cis-trans isomerase and molecular chaperone that operates in the secretory pathway to support the folding, post-translational maturation, and assembly of fibrillar extracellular matrix proteins (PMID:7493967, PMID:9461498, PMID:11071917, PMID:18786928). It contains four PPIase domains arranged in an extended linear structure, of which only one binds FK506, and accelerates isomerization of prolyl peptide bonds as well as the in vitro refolding of type III collagen (PMID:9461498). Beyond its catalytic activity, FKBP65 functions as a bona fide chaperone, suppressing thermal aggregation of model substrates and delaying type I collagen fibril formation (PMID:18786928), and it binds tropoelastin in the ER to modulate the kinetics of tropoelastin self-assembly through a PPIase-independent mechanism (PMID:9442105, PMID:21102654, PMID:24106871). Its central physiological role is to enable mature collagen crosslinking: FKBP65 is required for hydroxylation of collagen telopeptide lysines, and its PPIase activity positively modulates lysyl hydroxylase 2 (LH2) within a shared protein complex that also includes HSP47 and BiP, thereby controlling formation of hydroxylysine-aldehyde-derived crosslinks (PMID:22718341, PMID:23712425, PMID:28378777, PMID:28177155). Loss of FKBP65 impairs procollagen secretion and depletes telopeptide hydroxylysine crosslinks, and tissue-specific deletion in mice degrades bone quality and biomechanical strength and produces tendon fibrosis with ectopic Hedgehog-driven chondrogenesis (PMID:20362275, PMID:24777781, PMID:28206698, PMID:34161280); loss-of-function FKBP10 mutations cause the human collagen-fragility disorders osteogenesis imperfecta, Bruck syndrome, and Kuskokwim syndrome (PMID:22949511, PMID:23712425). In cancer settings FKBP10 acquires additional activities: its PPIase function promotes ribosome-associated translational elongation at proline codons (PMID:32187554), it binds LDHA to enhance Y10 phosphorylation and the Warburg effect (PMID:38233415), and it binds prelamin A to restrict its nuclear entry and drive tumor invasion (PMID:39781460). Across multiple fibrotic and tumor contexts FKBP10 acts through HSP47 to engage TGF-β/SMAD and AKT-CREB signaling (PMID:28774593, PMID:33557829, PMID:40316212).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1995 High

    Establishing that FKBP65 is a catalytically active prolyl isomerase defined its core enzymatic identity and distinguished it from cyclosporin-sensitive immunophilins.

    Evidence Recombinant protein PPIase assay with peptide substrate plus FK506/rapamycin/CsA inhibitor specificity

    PMID:7493967

    Open questions at the time
    • Physiological substrates not identified
    • Role of glycosylation and phosphorylation not defined
    • Function of the four domains not dissected
  2. 1998 High

    Structural characterization and a collagen refolding assay showed FKBP65 acts directly on a physiological collagen substrate, linking its PPIase activity to matrix protein folding.

    Evidence Analytical ultracentrifugation, peptide PPIase assays, and in vitro type III collagen refolding with FK506/CsA inhibition

    PMID:9461498

    Open questions at the time
    • In vivo collagen substrate not demonstrated
    • Roles of the three FK506-insensitive domains unresolved
  3. 1998 High

    Identification of tropoelastin as an ER binding partner extended FKBP65's role to a second matrix substrate and placed it in a transient pre-Golgi chaperone complex.

    Evidence Chemical cross-linking and co-IP from intact chondrocytes with BiP co-precipitation

    PMID:9442105

    Open questions at the time
    • Whether binding is PPIase-dependent not tested here
    • Functional consequence for tropoelastin maturation not yet shown
  4. 1998 Medium

    A reported FKBP65-hsp90-c-Raf-1 complex linked the protein to signal transduction, but this activity sits apart from its ER-luminal collagen functions.

    Evidence Co-IP and GST-FKBP65 pulldown with purified Raf proteins, Xenopus oocyte assay

    PMID:9438387

    Open questions at the time
    • Topological inconsistency with ER-luminal localization not reconciled
    • Not independently confirmed in later timeline studies
    • Functional relevance to FKBP65 physiology unclear
  5. 2000 High

    Rigorous localization established FKBP65 as an ER-luminal protein, framing all its substrate interactions as occurring in the secretory pathway.

    Evidence Subcellular fractionation, Triton X-114 phase separation, protease protection, and immunofluorescence

    PMID:11071917

    Open questions at the time
    • ER retention mechanism not defined
    • Does not address later cytosolic/ribosomal or nuclear-associated roles
  6. 2005 Medium

    Showing TGF-β1 transcriptionally upregulates FKBP65 in coordination with collagen and tropoelastin, and that it escapes the UPR, defined it as a matrix-program foldase rather than a generic stress chaperone.

    Evidence Fibroblast TGF-β1 treatment, Pol II chase, GGTI-298 dose-response, UPR assay

    PMID:16333983

    Open questions at the time
    • Transcription factors mediating induction not identified
    • Link between geranylgeranylation requirement and FKBP65 expression mechanistically unresolved
  7. 2008 High

    Reconstituted chaperone assays established that FKBP65 prevents substrate aggregation independent of its catalytic site, separating chaperone from isomerase functions.

    Evidence Citrate synthase thermal aggregation, rhodanese refolding, collagen fibril formation, gelatin-Sepharose isolation

    PMID:18786928

    Open questions at the time
    • Structural basis of chaperone activity not defined
    • Relative contribution of chaperone vs PPIase activity in vivo unresolved
  8. 2010 Medium

    Patient loss-of-function studies and a PPIase-independent tropoelastin coacervation assay tied FKBP65 to procollagen secretion in disease and refined its mechanism on elastin.

    Evidence Patient fibroblast secretion analysis; in vitro turbidimetric coacervation with rapamycin controls

    PMID:20362275 PMID:21102654

    Open questions at the time
    • Molecular cause of secretion defect not pinpointed in 2010
    • In vivo relevance of tropoelastin coacervation modulation untested
  9. 2011 Medium

    Demonstration that ER Ca2+ release triggers ERAD-mediated FKBP65 turnover via an EF-hand-dependent mechanism revealed regulated control of its abundance.

    Evidence ER stress induction, proteasome inhibition, fractionation, EF-hand mutagenesis, FKBP65-GFP imaging

    PMID:21761186

    Open questions at the time
    • ERAD machinery components not identified
    • Physiological trigger for regulated degradation unclear
  10. 2012 High

    Mass spectrometry across patient cohorts and null cells pinpointed loss of collagen telopeptide lysyl hydroxylation as the central FKBP65 defect, distinguishing a specific crosslinking role from a general chaperone role.

    Evidence Patient/bone studies, MS of collagen crosslinks, electrophoresis, thermal stability, Raman, IF of matrix fibrils

    PMID:22718341 PMID:22949511

    Open questions at the time
    • Mechanism by which FKBP65 enables telopeptide hydroxylation not yet defined in 2012
    • Identity of the responsible hydroxylase not yet established here
  11. 2013 High

    Kuskokwim-syndrome PPIase-domain mutations linked the telopeptide hydroxylation defect to FKBP65 PPIase function and implicated lysyl hydroxylase 2 as the relevant enzyme, while binding studies refined the PPIase-independent tropoelastin role.

    Evidence Patient fibroblast MS crosslink analysis, in vitro fibril formation; tropoelastin binding affinity and self-assembly kinetics with PPIase controls

    PMID:23712425 PMID:24106871

    Open questions at the time
    • Direct FKBP65-LH2 complex not yet demonstrated in 2013
    • How PPIase activity modulates LH2 not mechanistically resolved
  12. 2013 Medium

    Discovery that FKBP10 levels tune the folding-versus-degradation balance for mutant glucocerebrosidase broadened its role to ER proteostasis network regulation beyond matrix proteins.

    Evidence Proteomics, siRNA knockdown, glucocerebrosidase activity assay in Gaucher fibroblasts

    PMID:23434032

    Open questions at the time
    • Direct interaction with glucocerebrosidase not shown
    • Generality across other ER clients untested
  13. 2014 High

    Genetic knockout in mice and an HSP47-mutation study confirmed FKBP65's in vivo requirement for telopeptide crosslinking and placed FKBP65 and HSP47 in a common procollagen-maturation pathway.

    Evidence Fkbp10-/- MEFs and calvarial collagen MS; SERPINH1 patient cells with HSP47-FKBP65 co-IP and localization

    PMID:24777781 PMID:25510505

    Open questions at the time
    • Stoichiometry and organization of the FKBP65-HSP47 complex unresolved in 2014
    • Whether HSP47 stabilizes FKBP65 generally or only in disease unclear
  14. 2017 High

    Separation-of-function reconstitution and complex-detection assays established that FKBP65 PPIase activity positively modulates LH2 within an HSP47-FKBP65-BiP complex, defining the molecular mechanism for collagen crosslinking and translating it into bone quality and tendon phenotypes.

    Evidence Fkbp10-null MEF reconstitution with WT vs PPIase-mutant FKBP65, crosslink MS, co-IP/PCA/co-IF; OI patient cell LH2 assays; conditional osteoblast KO with μCT/Raman/SAXS/mechanics

    PMID:28177155 PMID:28206698 PMID:28378777

    Open questions at the time
    • Direct enzymatic mechanism by which PPIase activity enhances LH2 not resolved
    • Whether FKBP65 acts on LH2 itself or on the collagen substrate near LH2 unclear
  15. 2017 Medium

    Knockdown in scar fibroblasts linked FKBP10 to myofibroblast transition via TGF-β/Smad signaling, extending its role into fibrosis regulation.

    Evidence siRNA in hypertrophic scar fibroblasts with α-SMA/ECM/Smad readouts and in vivo scar model

    PMID:28774593

    Open questions at the time
    • Direct molecular link between FKBP10 and Smad pathway not defined here
    • Whether effect is PPIase-dependent untested
  16. 2018 Medium

    Collagen VI rescue experiments showed FKBP10 controls fibroblast adhesion and migration chiefly through collagen VI synthesis, adding another matrix substrate.

    Evidence siRNA, IF, proximity ligation assay, scratch/time-lapse migration, collagen VI coating rescue

    PMID:29673351

    Open questions at the time
    • Direct FKBP10-collagen VI biochemical interaction not quantified
    • Whether collagen VI handling requires PPIase activity untested
  17. 2020 Medium

    Ribosome association and ribosome profiling revealed a PPIase-dependent role for FKBP10 in translational elongation at proline codons, a function distinct from its ER chaperone activity.

    Evidence Gain/loss-of-function in lung cancer cells, ribosome co-IP, ribosome profiling, PPIase-domain dependency

    PMID:32187554

    Open questions at the time
    • Topological reconciliation with ER-luminal localization unaddressed
    • Direct ribosomal contact site not mapped
  18. 2021 High

    Tendon-specific deletion connected FKBP65 loss to ectopic Hedgehog-driven chondrogenesis, and glioma studies tied FKBP10-HSP47 binding to AKT-CREB-PCNA proliferative signaling.

    Evidence Tendon/ligament conditional KO with crosslink MS, Gli1 IHC, genetic Hh rescue, gait analysis; glioma GST pulldown/co-IP and pathway analysis with xenograft

    PMID:33557829 PMID:34161280

    Open questions at the time
    • Mechanism linking collagen crosslinking loss to Hh activation not fully defined
    • Whether the glioma proliferative effect requires PPIase activity untested
  19. 2024 Medium

    Direct LDHA binding and an fkbp10a zebrafish knockout extended FKBP10 mechanisms into metabolic reprogramming and confirmed conserved control of collagen lysyl hydroxylation with a Bmpr1aa modifier.

    Evidence Co-IP of FKBP10-LDHA, Y10 phosphorylation and histone lactylation assays, PPIase dependency in ccRCC; zebrafish KO with crosslink MS, EM, and modifier mapping

    PMID:38233415 PMID:39566080

    Open questions at the time
    • Whether FKBP10 directly catalyzes a step in LDHA activation unresolved
    • How a luminal chaperone accesses cytosolic LDHA unexplained
  20. 2025 Medium

    Prelamin A binding, VPS4A/RAS engagement, and HSP47/SMAD3 regulation defined further FKBP10 functions in tumor invasion and fibrosis across bladder cancer, hepatic stellate cells, and muscle contracture.

    Evidence Co-IP of FKBP10-prelamin A with fractionation and invasion assays; LC-MS/MS and co-IP of VPS4A with in vivo AAV knockdown; co-IP of HSP47 with SMAD3/autophagy readouts and epistasis rescue

    PMID:39781460 PMID:40316212 PMID:42102670

    Open questions at the time
    • Whether these interactions require PPIase activity not uniformly tested
    • Cross-context unification of these partner interactions unresolved
    • Subcellular site of prelamin A and VPS4A interactions unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single ER-luminal isomerase mechanistically supports such diverse functions — LH2-dependent collagen crosslinking, ribosomal translation elongation, LDHA activation, and prelamin A handling — and whether the non-ER activities reflect distinct localization pools remains unresolved.
  • No structural model of FKBP65 engaging LH2 or collagen telopeptides
  • Topological basis for cytosolic/ribosomal and nuclear-associated functions unexplained
  • Whether cancer-context partners are direct catalytic substrates untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016853 isomerase activity 5 GO:0044183 protein folding chaperone 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-1474244 Extracellular matrix organization 4 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3
Partners
HSP90HSPA5LDHALMNAPLOD2RAF1SERPINH1VPS4A
Complex memberships
HSP47-FKBP65-BiP ER chaperone complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 FKBP65 (FKBP10) is a novel 65-kDa FK506-binding protein with four predicted peptidyl-prolyl cis-trans isomerase (PPIase) domains. Recombinant FKBP65 accelerates isomerization of the prolyl peptide bond (N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide substrate) with catalytic efficiency similar to other FKBPs; this activity is inhibited by FK506 and rapamycin but not cyclosporin A. FKBP65 is also a glycoprotein and phosphoprotein. Recombinant protein expression, PPIase activity assay, FK506/rapamycin/CsA inhibition, immunoprecipitation, [32P] orthophosphate labeling, Northern blot The Journal of biological chemistry High 7493967
1998 Chicken FKBP65 has four PPIase domains arranged in a linear extended structure (~26 nm length, ~3 nm diameter) as shown by analytical ultracentrifugation. Only one of the four domains is inhibited by FK506 (and uniquely by cyclosporin A). FKBP65 catalyzes refolding of type III collagen in vitro (kcat/Km = 4.3×10³ M⁻¹s⁻¹), demonstrating direct collagen-PPIase activity. Analytical ultracentrifugation, PPIase activity assay with peptide substrates, FK506/CsA inhibition, in vitro collagen refolding assay The Biochemical journal High 9461498
1998 FKBP65 was identified as a binding partner of tropoelastin in the secretory pathway. Chemical cross-linking and co-immunoprecipitation from intact fetal bovine auricular chondrocytes showed FKBP65 and BiP co-precipitate with tropoelastin. The association occurs in the ER and is disrupted before the Golgi, suggesting FKBP65 acts as an ER chaperone for tropoelastin folding prior to secretion. Bifunctional chemical cross-linking in intact cells, co-immunoprecipitation, SDS-PAGE, microsequencing, brefeldin A and ALLN treatment The Journal of cell biology High 9442105
1998 FKBP65 forms immune complexes with hsp90 and the serine/threonine kinase c-Raf-1. The NH2-terminal regulatory domain of c-Raf-1 is required for interaction with FKBP65. GST-FKBP65 pulldown confirmed that full-length FKBP65 interacts with c-Raf-1 but not B-Raf. Association with c-Raf-1 correlates with v-H-RasV12-stimulated activation kinetics in Xenopus oocytes, linking FKBP65 to signal transduction. Co-immunoprecipitation, GST-FKBP65 pulldown with purified Raf proteins, Xenopus oocyte injection assay Cell growth & differentiation Medium 9438387
2000 FKBP65 is localized within the lumen of the ER (not cytosolic) as determined by subcellular fractionation, Triton X-114 phase separation, protease protection assays, and immunofluorescence. FKBP65 co-localizes with tropoelastin, and the two proteins dissociate before reaching the Golgi apparatus. Subcellular fractionation, Triton X-114 phase separation, protease protection assay, immunofluorescence microscopy, immunohistochemistry Molecular biology of the cell High 11071917
2005 FKBP65 expression is upregulated by TGF-β1 in human lung fibroblasts at the transcriptional level (not mRNA stabilization), and this response is blocked by GGTI-298 (a geranylgeranyl transferase I inhibitor), similar to type I collagen and tropoelastin. FKBP65 does not undergo the unfolded protein response, distinguishing its regulation from general ER stress foldases. Fibroblast culture with TGF-β1 treatment, RNA polymerase II inhibitor chase, GGTI-298 dose-response, UPR assay Cell stress & chaperones Medium 16333983
2008 FKBP65 acts as a molecular chaperone: it is a monomer in solution, inhibits thermal aggregation of citrate synthase, promotes refolding of denatured rhodanese, and delays in vitro fibril formation of type I collagen (indicating interaction with triple-helical collagen). Chaperone activity is comparable to protein-disulfide isomerase. FKBP65 can be isolated from chick embryos on a gelatin-Sepharose column. Analytical ultracentrifugation, thermal aggregation assay (citrate synthase), rhodanese refolding/aggregation assay, in vitro collagen fibril formation assay, gelatin-Sepharose affinity chromatography The Journal of biological chemistry High 18786928
2010 Loss-of-function mutations in FKBP10 affect type I procollagen secretion in patient cells, identifying FKBP65 as required for normal procollagen secretion/processing in the ER. Patient fibroblast studies, procollagen secretion analysis in cells homozygous for FKBP10 mutations American journal of human genetics Medium 20362275
2010 Recombinant FKBP65 markedly promotes initiation of tropoelastin coacervation in vitro at a 1:2 molar ratio (TE:FKBP65) and retards maturation of aggregates. This effect is unaffected by rapamycin, demonstrating that PPIase activity of FKBP65 is not required for modulating tropoelastin self-assembly. In vitro turbidimetric coacervation assay with recombinant FKBP65 and chicken aorta tropoelastin, rapamycin inhibition, comparison to FKBP12 Biochemistry and cell biology Medium 21102654
2011 ER stress signals that activate IP3R-mediated ER Ca²⁺ release cause rapid proteasomal degradation of FKBP65 via retrotranslocation (ERAD). Inhibiting IP3R-mediated ER Ca²⁺ release blocks this proteolysis. A defect in the EF1 Ca²⁺-binding EF-hand domain of FKBP65 leads to diminished ER protein levels that are restored by proteasome inhibition; the EF2 mutation does not confer this phenotype. ER stress induction, proteasome inhibition, cellular fractionation, live imaging of FKBP65-GFP, EF-hand site-directed mutagenesis, immunoblotting Cell stress & chaperones Medium 21761186
2012 Loss of FKBP65 (due to FKBP10 mutations) results in diminished hydroxylation of telopeptide lysyl residues of type I collagen that are involved in intermolecular cross-link formation in bone. Procollagen secretion is slightly delayed and stabilization of the intact trimer is incomplete. Patient fibroblast/bone studies, mass spectrometry of collagen cross-links, collagen electrophoresis, multiple family cohort Human molecular genetics High 22949511
2012 Absence of FKBP65 (FKBP10 null mutation) dramatically decreases collagen deposited in culture matrix despite normal collagen secretion. Mass spectrometry shows absence of hydroxylation of collagen telopeptide lysine required for cross-linking. Normal collagen chain incorporation, helix folding, and Tm indicate a minimal general collagen chaperone role for FKBP65, but a specific requirement for telopeptide lysyl hydroxylase activity or substrate access. Patient fibroblast studies, collagen electrophoresis, mass spectrometry, thermal stability (Tm), Raman spectroscopy, immunofluorescence of matrix collagen fibrils Human mutation High 22718341
2013 FKBP65 mutations (Kuskokwim syndrome, p.Tyr293del in PPIase domain 3) result in substantially decreased hydroxylation of the telopeptide lysine (2–10% vs 60% in controls) and marked reduction in maturely cross-linked collagen in matrix. Collagen fibrils formed in vitro show subtle loosening of monomer packing. These findings indicate FKBP65 supports collagen telopeptide hydroxylation by lysyl hydroxylase 2, and does so via its PPIase function. Patient fibroblast analysis, mass spectrometry of collagen cross-links, in vitro fibril formation, immunofluorescence, collagen matrix deposition assay Human mutation High 23712425
2013 Both elastin-binding protein (EBP) and FKBP65 bind tropoelastin with strong affinity (FKBP65 Kd ~4-fold higher than EBP). Both proteins modify the kinetics of tropoelastin self-assembly in vitro by limiting growth and maturation of aggregates. The ability of FKBP65 to modulate tropoelastin self-assembly is independent of its PPIase enzymatic activity. In vitro binding affinity measurements, in vitro tropoelastin self-assembly kinetics assay, PPIase inhibitor controls Biochemistry Medium 24106871
2013 Increased FKBP10 levels in Gaucher disease fibroblasts accelerate mutant glucocerebrosidase degradation over folding/trafficking. Decreased ER FKBP10 concentration leads to more mutant enzyme partitioning into the calnexin pro-folding pathway, enhancing folding and activity. This establishes FKBP10 as a regulator of ER proteostasis network balance for lysosomal enzymes. Mass spectrometry proteomics, siRNA knockdown, glucocerebrosidase activity assay, Gaucher fibroblast model Chemistry & biology Medium 23434032
2014 Fkbp10-null mouse embryonic fibroblasts show retention of procollagen in the cell layer and associated dilated ER. Type I calvarial collagen from Fkbp10-/- mice shows reduced stable crosslink formation at telopeptide lysines, confirming FKBP65 is required for telopeptide lysine crosslinking in vivo. Fkbp10-/- knockout mouse model, immunofluorescence, electron microscopy (dilated ER), mass spectrometry of collagen cross-links from calvarial bone Human molecular genetics High 24777781
2014 HSP47 and FKBP65 act cooperatively during posttranslational maturation of type I procollagen. A destabilizing mutation in HSP47 (SERPINH1) causes secondary mislocalization and destabilization of FKBP65. FKBP65 and HSP47 fail to properly interact in mutant HSP47 cells, placing both in a common cellular pathway for procollagen maturation. Patient fibroblast studies (SERPINH1 mutation), co-immunoprecipitation of HSP47 and FKBP65, immunofluorescence localization, collagen analysis Human molecular genetics Medium 25510505
2017 FKBP65 PPIase activity is required to positively modulate LH2 (lysyl hydroxylase 2) enzymatic activity for hydroxylysine-aldehyde-derived collagen cross-link (HLCC) formation. In Fkbp10-null fibroblasts, HLCCs are diminished and LCCs increased without change in LH2 protein levels; reconstitution with wild-type but not PPIase-domain-mutant FKBP65 rescues the HLCC/LCC ratio. LH2 and FKBP65 are part of a common protein complex. Fkbp10-null vs wild-type MEFs, collagen cross-link mass spectrometry, reconstitution with WT vs PPIase-mutant FKBP65, co-immunoprecipitation, protein-fragment complementation assay, co-immunofluorescence Scientific reports High 28378777
2017 An ER chaperone complex consisting of HSP47, FKBP65, and BiP modulates lysyl hydroxylase 2 (LH2) activity on type I collagen C-telopeptides. FKBP65 and HSP47 modulate LH2 activity (either favoring or repressing it), and BiP enhances complex formation. Co-immunoprecipitation identifying HSP47-FKBP65-BiP complex, LH2 activity assays in OI patient cells, loss-of-function studies Journal of bone and mineral research High 28177155
2017 Osteoblast-specific conditional deletion of Fkbp10 in mice reduces mature hydroxylysine-aldehyde collagen cross-linking in bone (by mass spectrometry) without affecting bone quantity or mineralization degree, but reduces mineral-to-matrix ratio and crystal size (Raman spectroscopy and SAXS) and impairs biomechanical bone strength. Conditional Fkbp10 knockout (Col1a1-Cre), μCT, histomorphometry, qBEI, mass spectrometry of collagen cross-links, Raman spectroscopy, SAXS, mechanical testing Journal of bone and mineral research High 28206698
2017 FKBP10 knockdown in hypertrophic scar fibroblasts reduces α-smooth muscle actin expression, extracellular matrix component production, TGF-β1 expression, and attenuates Smad signaling pathway activation, demonstrating a role for FKBP65 in regulating fibroblast-to-myofibroblast transition via the TGF-β/Smad axis. siRNA knockdown in human hypertrophic scar fibroblasts, α-SMA and ECM protein expression analysis, Smad signaling pathway analysis, in vivo mouse scar model with siRNA The Journal of investigative dermatology Medium 28774593
2018 FKBP10 knockdown attenuates adhesion and migration of primary human lung fibroblasts. FKBP10 co-localizes with collagen VI (by IF and proximity ligation assay), and coating culture dishes with collagen VI abolishes the migration defect caused by FKBP10 deficiency, establishing that FKBP10 regulates fibroblast migration primarily through collagen VI synthesis. siRNA knockdown, immunofluorescence, proximity ligation assay, scratch assay, single-cell time-lapse tracking, collagen VI rescue experiment Respiratory research Medium 29673351
2020 FKBP10 promotes lung cancer cell growth and stemness via its PPIase activity. FKBP10 interacts with ribosomes, and its downregulation causes reduced translation elongation at the beginning of open reading frames, particularly at proline-encoding codons. Gain- and loss-of-function assays confirmed PPIase activity is required for these translational effects. Gain/loss-of-function in lung cancer cells and mouse tumor models, ribosome co-immunoprecipitation, ribosome profiling/translation elongation assay, PPIase-domain dependency studies Cell reports Medium 32187554
2021 Conditional deletion of Fkbp10 in tendons and ligaments reduces telopeptide lysyl hydroxylation of type I procollagen and collagen cross-linking in tendons, leading to fibrosis, inflammation, and ectopic chondrogenesis with enhanced Gli1 expression (Hedgehog signaling). Genetic inhibition of the Hh pathway attenuates ectopic chondrogenesis and joint deformities and restores gait in Fkbp10 mutants. Tendon/ligament-specific Fkbp10 conditional KO mouse, mass spectrometry of collagen cross-links, immunohistochemistry (Gli1), genetic Hh pathway inhibition, gait analysis Proceedings of the National Academy of Sciences High 34161280
2021 FKBP10 interacts with HSP47 (co-immunoprecipitation, GST pulldown, co-immunofluorescence) in glioma cells, and this interaction activates the AKT-CREB-PCNA signaling axis to promote cell proliferation. GST pulldown, co-immunoprecipitation, confocal immunofluorescence, western blotting (p-AKT, p-CREB, PCNA), CCK-8, colony formation, xenograft tumor model Journal of biomedical science Medium 33557829
2024 FKBP10 binds directly to LDHA (lactate dehydrogenase A) through its C-terminal region and enhances LDHA-Y10 phosphorylation, leading to hyperactive Warburg effect and accumulation of histone lactylation in ccRCC cells. This function depends on FKBP10's PPIase domains. Co-immunoprecipitation (direct binding), in vitro/in vivo proliferation and metastasis assays, LDHA phosphorylation analysis, histone lactylation measurement, PPIase domain dependency, in vivo xenograft Cell death & disease Medium 38233415
2024 fkbp10a knockout zebrafish show decreased type I collagen lysyl hydroxylation by mass spectrometry and wide skeletal variability, with enlarged collagen fibrils and disturbed elastin layers ultrastructurally. Bmpr1aa was identified as a modifier gene whose reduced expression correlates with increased skeletal severity. fkbp10a knockout zebrafish, mass spectrometry of collagen lysyl hydroxylation, electron microscopy, whole-exome sequencing, SNP-based linkage analysis, transcriptome analysis Journal of bone and mineral research Medium 39566080
2025 FKBP10 interacts with prelamin A and hinders nuclear entry of prelamin A, leading to decreased nuclear lamin A levels and nuclear atypia in bladder cancer cells. FKBP10 promotes tumor cell invasion and migration but not proliferation through this FKBP10/prelamin A/lamin A axis. Co-immunoprecipitation (FKBP10-prelamin A interaction), nuclear/cytoplasmic fractionation, lamin A immunofluorescence, invasion/migration assays, loss-of-function knockdown International journal of biological sciences Medium 39781460
2025 FKBP10 knockdown in hepatic stellate cells (LX-2) attenuates HSC activation, reduces ECM production, and promotes apoptosis. FKBP10 interacts with VPS4A (identified by LC-MS/MS and co-IP), which may facilitate RAS pathway activation. FKBP10 deficiency suppresses RAS signaling in primary HSCs by transcriptomic analysis. In vivo AAV-mediated HSC-specific FKBP10 knockdown reduces fibrosis in CCl4 and BDL mouse models. siRNA knockdown in LX-2 cells, in vivo AAV6-GFAP-shFKBP10, LC-MS/MS proteomics, co-immunoprecipitation (VPS4A), transcriptomic sequencing, immunohistochemistry Biochemical and biophysical research communications Medium 42102670
2025 FKBP10 knockdown inactivates the HSP47/SMAD3 signaling pathway in gluteal muscle contracture fibroblasts: FKBP10 interacts with HSP47, and its knockdown reduces HSP47 and phospho-SMAD3 levels, inhibits fibrosis markers, and ameliorates autophagy defects. HSP47 overexpression reverses the effects of FKBP10 knockdown. Co-immunoprecipitation (FKBP10-HSP47), western blotting (p-SMAD3, autophagy markers), siRNA knockdown, TGF-β1 stimulation, GMC rat model with FKBP10 knockdown The American journal of pathology Medium 40316212

Source papers

Stage 0 corpus · 63 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. American journal of human genetics 227 20362275
2011 Mutations in FKBP10 cause recessive osteogenesis imperfecta and Bruck syndrome. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 131 20839288
2012 Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen. Human molecular genetics 114 22949511
2008 The rough endoplasmic reticulum-resident FK506-binding protein FKBP65 is a molecular chaperone that interacts with collagens. The Journal of biological chemistry 104 18786928
2012 Absence of FKBP10 in recessive type XI osteogenesis imperfecta leads to diminished collagen cross-linking and reduced collagen deposition in extracellular matrix. Human mutation 80 22718341
1998 Identification of tropoelastin as a ligand for the 65-kD FK506-binding protein, FKBP65, in the secretory pathway. The Journal of cell biology 65 9442105
2017 A Chaperone Complex Formed by HSP47, FKBP65, and BiP Modulates Telopeptide Lysyl Hydroxylation of Type I Procollagen. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 58 28177155
2011 Mutations in FKBP10 cause both Bruck syndrome and isolated osteogenesis imperfecta in humans. American journal of medical genetics. Part A 57 21567934
2000 Developmental regulation of FKBP65. An ER-localized extracellular matrix binding-protein. Molecular biology of the cell 56 11071917
2014 Connective tissue alterations in Fkbp10-/- mice. Human molecular genetics 55 24777781
2024 FKBP10 promotes clear cell renal cell carcinoma progression and regulates sensitivity to the HIF2α blockade by facilitating LDHA phosphorylation. Cell death & disease 53 38233415
1995 Molecular cloning, DNA sequence analysis, and biochemical characterization of a novel 65-kDa FK506-binding protein (FKBP65). The Journal of biological chemistry 53 7493967
2014 HSP47 and FKBP65 cooperate in the synthesis of type I procollagen. Human molecular genetics 50 25510505
2013 Kuskokwim syndrome, a recessive congenital contracture disorder, extends the phenotype of FKBP10 mutations. Human mutation 49 23712425
1998 Chicken FK506-binding protein, FKBP65, a member of the FKBP family of peptidylprolyl cis-trans isomerases, is only partially inhibited by FK506. The Biochemical journal 48 9461498
2020 FKBP10 Regulates Protein Translation to Sustain Lung Cancer Growth. Cell reports 42 32187554
2021 FKBP10 promotes proliferation of glioma cells via activating AKT-CREB-PCNA axis. Journal of biomedical science 40 33557829
2022 circREEP3 Drives Colorectal Cancer Progression via Activation of FKBP10 Transcription and Restriction of Antitumor Immunity. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 37 35233964
2017 Inhibition of FKBP10 Attenuates Hypertrophic Scarring through Suppressing Fibroblast Activity and Extracellular Matrix Deposition. The Journal of investigative dermatology 34 28774593
2018 FK506-binding protein 10 (FKBP10) regulates lung fibroblast migration via collagen VI synthesis. Respiratory research 29 29673351
1998 The immunophilin FKBP65 forms an association with the serine/threonine kinase c-Raf-1. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 28 9438387
2015 Homozygous sequence variants in the FKBP10 gene underlie osteogenesis imperfecta in consanguineous families. Journal of human genetics 27 26538303
2011 Mutations in FKBP10 can cause a severe form of isolated Osteogenesis imperfecta. BMC medical genetics 27 22107750
2011 A novel splicing mutation in FKBP10 causing osteogenesis imperfecta with a possible mineralization defect. Bone 26 22061863
2019 FKBP10 functioned as a cancer-promoting factor mediates cell proliferation, invasion, and migration via regulating PI3K signaling pathway in stomach adenocarcinoma. The Kaohsiung journal of medical sciences 25 31868996
2013 FKBP10/FKBP65 expression in high-grade ovarian serous carcinoma and its association with patient outcome. International journal of oncology 25 23354471
2005 Developmental regulation and coordinate reexpression of FKBP65 with extracellular matrix proteins after lung injury suggest a specialized function for this endoplasmic reticulum immunophilin. Cell stress & chaperones 25 16333983
2013 Elastin binding protein and FKBP65 modulate in vitro self-assembly of human tropoelastin. Biochemistry 24 24106871
2011 A novel homozygous 5 bp deletion in FKBP10 causes clinically Bruck syndrome in an Indonesian patient. European journal of medical genetics 24 22085994
2017 Fkbp10 Deletion in Osteoblasts Leads to Qualitative Defects in Bone. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20 28206698
2015 Bruck syndrome - a rare syndrome of bone fragility and joint contracture and novel homozygous FKBP10 mutation. Endokrynologia Polska 20 25931047
2017 FKBP65-dependent peptidyl-prolyl isomerase activity potentiates the lysyl hydroxylase 2-driven collagen cross-link switch. Scientific reports 19 28378777
2011 Endoplasmic reticulum stress or mutation of an EF-hand Ca(2+)-binding domain directs the FKBP65 rotamase to an ERAD-based proteolysis. Cell stress & chaperones 18 21761186
2013 FKBP10 depletion enhances glucocerebrosidase proteostasis in Gaucher disease fibroblasts. Chemistry & biology 17 23434032
2016 Novel mutations in FKBP10 in Chinese patients with osteogenesis imperfecta and their treatment with zoledronic acid. Journal of human genetics 16 27762305
2021 Localized chondro-ossification underlies joint dysfunction and motor deficits in the Fkbp10 mouse model of osteogenesis imperfecta. Proceedings of the National Academy of Sciences of the United States of America 13 34161280
2021 Long-Term Follow-Up Outcomes of 19 Patients with Osteogenesis Imperfecta Type XI and Bruck Syndrome Type I Caused by FKBP10 Variants. Calcified tissue international 11 34173012
2017 Osteogenesis imperfecta type 3 in South Africa: Causative mutations in FKBP10. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 11 28492130
2010 Effect of FKBP65, a putative elastin chaperone, on the coacervation of tropoelastin in vitro. Biochemistry and cell biology = Biochimie et biologie cellulaire 11 21102654
2022 High VSX1 expression promotes the aggressiveness of clear cell renal cell carcinoma by transcriptionally regulating FKBP10. Journal of translational medicine 8 36463181
2011 Expression of FK506 binding protein 65 (FKBP65) is decreased in epithelial ovarian cancer cells compared to benign tumor cells and to ovarian epithelium. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 8 21399973
2023 Clinical features and molecular characterization of Chinese patients with FKBP10 variants. Molecular genetics & genomic medicine 7 36655627
2023 Subcellular Expression Patterns of FKBP Prolyl Isomerase 10 (FKBP10) in Colorectal Cancer and Its Clinical Significance. International journal of molecular sciences 7 37511172
2021 Oligogenic Inheritance of Monoallelic TRIP11, FKBP10, NEK1, TBX5, and NBAS Variants Leading to a Phenotype Similar to Odontochondrodysplasia. Frontiers in genetics 6 34149817
2018 Novel mutations of the SERPINF1 and FKBP10 genes in Chinese families with autosomal recessive osteogenesis imperfecta. International journal of molecular medicine 6 29512769
2016 Analysis of FKBP10, SERPINH1, and SERPINF1 genes in patients with osteogenesis imperfecta. Genetics and molecular research : GMR 6 27706701
2025 FKBP10 Promotes the Muscle Invasion of Bladder Cancer via Lamin A Dysregulation. International journal of biological sciences 5 39781460
2025 FKBP10 Silencing Alleviates Gluteal Muscle Contracture by Inhibiting Fibrosis and Restoring Autophagy via HSP47/SMAD3 Pathway Inactivation. The American journal of pathology 4 40316212
2024 A novel compound heterozygous variation in the FKBP10 gene causes Bruck syndrome without congenital contractures: A case report. Heliyon 4 38590901
2024 Bmpr1aa modulates the severity of the skeletal phenotype in an fkbp10-deficient Bruck syndrome zebrafish model. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 4 39566080
2020 New insights on the clinical variability of FKBP10 mutations. European journal of medical genetics 4 32531462
2024 Presentation of Rare Phenotypes Associated with the FKBP10 Gene. Genes 3 38927610
2018 Splicing defect in FKBP10 gene causes autosomal recessive osteogenesis imperfecta disease: a case report. BMC medical genetics 3 29801479
2016 Novel FKBP10 Mutation in a Patient with Osteogenesis Imperfecta Type XI. Fetal and pediatric pathology 3 27362741
2025 Construction and multi-omics analysis of ccRCC mitochondrial related gene machine learning model and validate of key gene FKBP10. International immunopharmacology 1 40939431
2023 Mutation In Fkbp10 Gene Cause Bruck Syndrome 1 (Brks1) In A Pakistani Family Of Pashtun Origin. Journal of Ayub Medical College, Abbottabad : JAMC 1 37422836
2017 Novel mutation of FKBP10 in a pediatric patient with osteogenesis imperfecta type XI identified by clinical exome sequencing. The application of clinical genetics 1 29158687
2026 Seropositive rheumatoid arthritis in osteogenesis imperfecta type XI (FKBP10 mutation): first case report and literature review. Orphanet journal of rare diseases 0 41530856
2026 FKBP10 promotes M2 polarization of macrophage via MEK/ERK/CXCL8 axis and facilitates tumor progression in clear cell renal cell carcinoma. International journal of biological sciences 0 41694575
2026 Pan-cancer analysis identifies FKBP10 as a regulator of tumor immunosuppression and therapeutic response. Translational oncology 0 41934915
2026 Integrative Multiomics and Single-Cell Analyses Identify FKBP10 as a Predictor of Radiotherapy Outcome in Colorectal Cancer. Human mutation 0 41969611
2026 Inhibition of FKBP10 attenuates hepatic stellate cell activation and liver fibrosis via RAS signaling. Biochemical and biophysical research communications 0 42102670
2025 Novel FKBP10 Mutation in Iranian Patients with Osteogenesis Imperfecta: Insights from Whole-Exome Sequencing to Molecular Dynamics. Iranian biomedical journal 0 41422392

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