Target antigen: Human FKBP65 (UniProt ID: Q96AY3), encoded by the FKBP10 gene.
Applications: Validated for Western blot (WB), immunohistochemistry (IHC), immunoprecipitation (IP), and ELISA .
Host species: Rabbit recombinant antibody (clonal: S94) .
Molecular weight: Detects bands at 65–70 kDa in WB .
FKBP65 regulates lysyl hydroxylase 2 (LH2), an enzyme critical for collagen cross-linking:
Dimerization role: FKBP65 enables LH2 dimer formation, essential for its enzymatic activity. Knockdown or inhibition (e.g., tacrolimus) reduces LH2 dimerization by 75% .
PPIase dependency: Mutations in FKBP65’s peptidyl-prolyl isomerase (PPIase) domains disrupt collagen cross-link switching (HLCC-to-LCC ratio) .
Co-localization: Proximity ligation assays confirm FKBP65-LH2 complexes in fibrotic kidney tissues .
| Cancer Type | FKBP65 Expression | Clinical Correlation |
|---|---|---|
| Ovarian (HGSC) | Underexpressed | Poor survival (HR = 2.1) |
| Bladder | Overexpressed | Muscle invasion promotion |
| Lung | Reactivated | Stromal stiffness/metastasis |
In high-grade ovarian serous carcinomas (HGSCs), loss of FKBP65 correlates with reduced collagen type I (COL1A1) and worse prognosis .
FKBP65 knockdown in bladder cancer models dysregulates lamin A, enhancing invasiveness .
Lung development: FKBP65 colocalizes with tropoelastin and collagen in postnatal mouse lung, peaking during matrix synthesis phases .
Fibrosis: Bleomycin-induced lung injury reactivates FKBP65 expression, mirroring collagen I upregulation .
Targeting PPIase activity: FKBP65’s role in LH2 dimerization offers a strategy to modulate collagen cross-linking in fibrosis and cancer .
Drug challenges: Tacrolimus only partially inhibits FKBP65 (~25% efficacy), highlighting the need for more potent inhibitors .
FKBP65 (FK506-binding protein 12.6 kDa) is a peptidyl-prolyl cis-trans isomerase (PPIase) that accelerates protein folding by catalyzing the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. It functions as a co-chaperone, negatively modulating thermotolerance through interaction with FKBP62 and subsequent reduction in heat shock factor A2 (HSFA2)-mediated accumulation of small heat shock proteins (sHSPs). FKBP65 plays a crucial role in intracellular acid stress tolerance by maintaining pH homeostasis. Furthermore, it may participate in transcriptional regulatory pathways in response to pathogen infection.