Affinage

Showing FKBP1B — FKBP12.6 is a alias.

FKBP1B

Peptidyl-prolyl cis-trans isomerase FKBP1B · UniProt P68106

Length
108 aa
Mass
11.8 kDa
Annotated
2026-06-09
82 papers in source corpus 47 papers cited in narrative 48 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FKBP1B (FKBP12.6/calstabin2) is a peptidyl-prolyl cis-trans isomerase that functions as a high-affinity (Kd ~0.7 nM), selective regulatory subunit of the cardiac ryanodine receptor RyR2, stabilizing the channel's closed state to suppress diastolic Ca2+ leak and govern excitation-contraction coupling (PMID:8702774, PMID:20431056, PMID:27670942). Unlike FKBP12, only FKBP12.6 binds and rebinds RyR2 (not RyR1), and it assembles into an SR macromolecular complex with PKA, the phosphatases PP1 and PP2A, and the anchoring protein mAKAP (PMID:8702774, PMID:10830164). The interaction maps principally to the RyR2 N-terminal domain (residues 305–1937), with cryo-EM showing that FKBP12.6 docks at the cytoplasmic clamp region and rigidifies the HD2 domain to lock the closed conformation (PMID:12446682, PMID:16214874, PMID:28536302). Gain- and loss-of-function studies establish the functional consequence directly: FKBP12.6 overexpression reduces Ca2+ spark frequency, raises SR Ca2+ load, and prevents triggered arrhythmias, whereas its loss or dissociation increases RyR2 sensitivity to Ca2+ triggers and SR Ca2+ leak (PMID:11157671, PMID:28077437, PMID:18378612). Loss of FKBP12.6 in mice produces sex-dependent cardiac hypertrophy, atrial fibrillation, and aberrant Ca2+ release, and the protein further protects against AngII-induced hypertrophy by restraining calcineurin/NFAT, CaMKII/MEF-2, and AKT/mTOR signaling (PMID:11907581, PMID:18598963, PMID:29682889). Dissociation is driven by cADPR signaling and by CaMKII-dependent phosphorylation of RyR2 at S2814, but not by PKA phosphorylation at S2808, which does not alter FKBP12.6 binding (PMID:14715536, PMID:19578067, PMID:20431056, PMID:22158709). Beyond RyR2, FKBP12.6 directly binds the IP3 receptor in detrusor muscle, the BMP/TGF-β type I receptor ALK2 via its GS domain, and Glomulin, and it acts in non-cardiac settings including glucose-stimulated insulin secretion, smooth-muscle Ca2+ release, and anti-adipogenesis downstream of miR-34a (PMID:40051354, PMID:33572801, PMID:31490997, PMID:18466757, PMID:15036951, PMID:26471303). Its abundance is set post-translationally through Glomulin/NR3C1-dependent ubiquitination (PMID:40943170).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 1996 High

    Established that FKBP12.6, distinct from the closely related FKBP12, is the physiological FKBP partner of the cardiac RyR2, defining its binding selectivity as the basis for isoform-specific channel regulation.

    Evidence radiolabeled FKBP12/12.6 binding and cosedimentation with stripped cardiac SR membranes

    PMID:8702774

    Open questions at the time
    • Did not localize the binding site on RyR2
    • Did not establish functional consequence of binding
  2. 2000 High

    Placed FKBP12.6 within an SR macromolecular signaling complex and proposed a regulatory model in which PKA phosphorylation dissociates it to increase channel activity, linking the complex to heart failure.

    Evidence cosedimentation, reciprocal Co-IP, single-channel recordings, and failing human heart tissue

    PMID:10830164

    Open questions at the time
    • The PKA-induced dissociation claim was subsequently disputed
    • Stoichiometry and phospho-site dependence not resolved here
  3. 2000 High

    Showed quantitatively that FKBP12.6 loss in failing hearts arises from reduced binding-site occupancy/expression rather than altered affinity, mechanistically connecting FKBP12.6 depletion to pathological Ca2+ leak.

    Evidence [3H]dihydro-FK506 and [3H]ryanodine binding, stopped-flow Ca2+ release, and Western blot in failing canine/native heart tissue

    PMID:11044432 PMID:11054478

    Open questions at the time
    • Did not define the trigger for FKBP12.6 loss
    • Correlative in disease, not causal manipulation
  4. 2001 High

    Directly demonstrated by gain-of-function that FKBP12.6 stabilizes the closed RyR2 state, reducing SR Ca2+ leak and improving contractility.

    Evidence adenoviral FKBP12.6 overexpression in rabbit cardiomyocytes with Ca2+ leak and contractility readouts

    PMID:11157671

    Open questions at the time
    • Structural basis of stabilization not addressed
    • Single overexpression context
  5. 2002 High

    Genetic deletion established FKBP12.6 as a modulator of cardiac EC coupling with sex-dependent hypertrophy and identified it as the effector through which cADPR controls Ca2+ release across cardiac and smooth muscle.

    Evidence FKBP12.6 knockout mice with echocardiography, Ca2+ spark imaging, tamoxifen, and cADPR dialysis in cardiac/tracheal/coronary smooth muscle

    PMID:11893565 PMID:11907581 PMID:14592808

    Open questions at the time
    • Molecular mechanism of estrogen protection unresolved
    • Direct cADPR target within the complex not defined
  6. 2002 High

    Mapped the FKBP12.6 footprint on RyR2 to the N-terminal domain (residues 305–1937) and excluded the I2427-P2428 motif as the core site, providing the first structural localization of the interaction.

    Evidence GST pulldown with RyR2 deletion mutants in HEK293 cells; complementary quantitative Y2H of disease mutants

    PMID:12446682 PMID:12459180

    Open questions at the time
    • Did not resolve residue-level contacts
    • A separate C-terminal site was later proposed, creating an unresolved discrepancy
  7. 2003 High

    Linked FKBP12.6 deficiency to exercise-induced lethal ventricular arrhythmia and to CPVT mutations that weaken FKBP12.6 binding, framing FKBP12.6 dissociation as an arrhythmogenic mechanism.

    Evidence FKBP12.6 knockout mice with in vivo exercise testing, single-channel recordings of CPVT mutants, and radioligand binding

    PMID:12837242

    Open questions at the time
    • The stress-induced arrhythmia phenotype was later not reproduced in another knockout study
    • Causal chain from binding loss to arrhythmia incompletely defined
  8. 2003 High

    Demonstrated in heterologous cells that FKBP12.6 is sequestered to RyR2-bearing ER membranes and suppresses agonist-evoked Ca2+ release independent of resting Ca2+/ER load, establishing a cell-protective regulatory function.

    Evidence stable CHO lines expressing hRyR2 with confocal localization, Ca2+ imaging, rapamycin competition, and viability assays

    PMID:12443530 PMID:12754204

    Open questions at the time
    • Heterologous system may not recapitulate native stoichiometry
    • FKBP12 negative control behavior left mechanism of selectivity open
  9. 2004 High

    Resolved the PKA-phosphorylation controversy by showing S2808 phosphorylation does not dissociate FKBP12.6, while reconstitution confirmed FKBP12.6 (not FKBP12) suppresses spontaneous RyR2 activity and supports ordered CICR.

    Evidence phospho-specific Co-IP with S2808D mutant; reconstitution in dyspedic myotubes with DHPR/RyR2; competition binding to a C-terminal RyR2 construct

    PMID:14715536 PMID:15591045 PMID:16049053

    Open questions at the time
    • Reconciliation of N-terminal versus C-terminal binding sites not achieved
    • Did not identify the true dissociation trigger
  10. 2004 High

    Reinforced through multiple gain-of-function studies that FKBP12.6 reduces Ca2+ spark parameters while enhancing global Ca2+ transients and SR load, and extended its RyR2-selective role to pulmonary artery smooth muscle Ca2+ signaling.

    Evidence adenoviral overexpression in rat/rabbit cardiomyocytes with Ca2+ imaging and voltage clamp; FKBP12.6 KO with Ca2+/force readouts in pulmonary artery SMC

    PMID:14966299 PMID:15036951 PMID:15271664

    Open questions at the time
    • Tissue-specific differences in coupling not mechanistically unified
    • RyR2-selectivity over RyR1/3 and IP3R asserted but contacts undefined
  11. 2005 High

    Provided structural visualization that FKBP12.6 binds the cytoplasmic clamp region adjacent to domain 9 and alters RyR2 conformation in the transmembrane/clamp domains, connecting binding to gating control.

    Evidence cryo-EM 3D reconstruction and difference mapping of canine RyR2±FKBP12.6; orthogonal Y2H/Co-IP fragment analysis

    PMID:16049346 PMID:16214874

    Open questions at the time
    • Low resolution precluded atomic contacts
    • Conformational mechanism inferred, not dynamically resolved
  12. 2006 High

    Identified FKBP12.6 residues (notably Asp-37) governing RyR2 binding and engineered a mutant that binds phospho-mimetic RyR2 and rescues failing-heart function, providing a structure-guided therapeutic proof of concept.

    Evidence FKBP12.6 site-directed mutagenesis, Co-IP with RyR2-S2808D, and in vivo myocardial infarction rescue

    PMID:16481613

    Open questions at the time
    • Single lab, dependent on the contested PKA-dissociation framework
    • Generalizability of mutant rescue not established
  13. 2007 High

    Challenged the FKBP12.6-RyR2 gating paradigm by reporting that FKBP12.6 removal does not alter RyR2 single-channel properties or confer stress-induced arrhythmia, and that K201's action is FKBP12.6-independent.

    Evidence lipid-bilayer single-channel recordings, [3H]ryanodine binding, HEK293 SOICR imaging, and KO stress testing

    PMID:17313373 PMID:17921453

    Open questions at the time
    • Directly contradicts earlier arrhythmia findings, leaving the in vivo role context-dependent
    • Did not reconcile differing knockout phenotypes
  14. 2008 High

    Established causal roles for FKBP12.6 in atrial fibrillation susceptibility and in glucose-stimulated insulin secretion, broadening its physiological scope beyond ventricular EC coupling.

    Evidence FKBP12.6-/- mice with intracardiac electrography and tetracaine rescue; in vivo glucose tolerance, islet secretion, and Ca2+ imaging

    PMID:18466757 PMID:18598963

    Open questions at the time
    • Beta-cell Ca2+ channel target left to placement downstream of ATP
    • Atrial leak mechanism not yet tied to a specific phospho-site
  15. 2009 High

    Dissected the dissociation signals by showing cADPR—but not β-adrenergic/ISO stimulation—augments Ca2+ sparks through FKBP12.6, and demonstrated conditional cardiac FKBP12.6 overexpression prevents triggered ventricular tachycardia; also revealed FKBP12.6 effects on IK1/action potential duration and opposing insulin phenotypes.

    Evidence FKBP12.6 KO Ca2+ spark/force studies, conditional cardiac transgenic in vivo electrophysiology, patch clamp with calcineurin-mutant FKBP12.6, and KO glucose/insulin assays

    PMID:18378612 PMID:19333617 PMID:19578067 PMID:19805579

    Open questions at the time
    • Insulin secretion phenotype differed between knockout studies
    • Mechanism coupling FKBP12.6 to IK1 not fully defined
  16. 2010 High

    Provided definitive in situ binding kinetics (Kd ~0.7 nM for FKBP12.6 vs ~206 nM for FKBP12) and conclusively showed PKA phosphorylation does not change FKBP12.6 binding, settling the affinity and phospho-dependence questions.

    Evidence fluorescent binding and FRAP in permeabilized myocytes with Ca2+ spark readouts and quantitative immunoblot

    PMID:20431056

    Open questions at the time
    • Did not address which physiological trigger dissociates FKBP12.6
    • In situ measurement does not resolve binding-site geometry
  17. 2012 High

    Clarified the FKBP isoform paradox—FKBP12 activates/sensitizes RyR2 while FKBP12.6 antagonizes this—and placed FKBP12.6 downstream of the CHF1/Hey2 transcriptional program in cardiac EC coupling.

    Evidence single sheep RyR2 bilayer recordings with modeling; conditional CHF1/Hey2 KO with FK506 rescue and expression analysis

    PMID:22363773 PMID:22408025

    Open questions at the time
    • Mechanism by which CHF1/Hey2 controls FKBP12.6 transcription not defined
    • Competition dynamics of FKBP12 vs FKBP12.6 in vivo unresolved
  18. 2011 High

    Established by genetic epistasis that CaMKII phosphorylation of RyR2 at S2814—not PKA at S2808—mediates the atrial fibrillation arising from FKBP12.6 deficiency, defining the operative dissociation/leak pathway.

    Evidence FKBP12.6-/-:S2814A double-mutant mice with intracardiac stimulation and Ca2+ spark/wave imaging

    PMID:22158709

    Open questions at the time
    • Did not establish whether S2814 phosphorylation directly weakens FKBP12.6 binding
    • Ventricular versus atrial pathway differences not fully mapped
  19. 2017 High

    Refined the structural mechanism (HD2-domain rigidification stabilizing the closed state) and demonstrated functionally that FKBP12.6 absence increases LCC-RyR coupling fidelity and spark frequency without changing LCC gating, linking the molecular effect to arrhythmogenic Ca2+ waves.

    Evidence cryo-EM of rabbit RyR2-FKBP12.6 with conformational analysis; KO patch clamp with confocal Ca2+ spark and LCC-RyR coupling kinetics

    PMID:28077437 PMID:28536302

    Open questions at the time
    • Resolution insufficient for full atomic phospho-domain modeling
    • How HD2 rigidification propagates to the pore not mechanistically traced
  20. 2016 High

    Confirmed that FKBP12.6 retains intrinsic peptidyl-prolyl cis-trans isomerase catalytic activity and characterized its conformational flexibility, distinguishing its enzymatic function from its scaffolding role at RyR2.

    Evidence total chemical synthesis with enzymatic assay and crystallography; high-resolution crystal structures plus NMR conformational exchange analysis

    PMID:24598733 PMID:27670942

    Open questions at the time
    • No physiological PPIase substrate identified
    • Relationship of catalytic activity to channel regulation undefined
  21. 2021 High

    Expanded the FKBP12.6 interactome beyond RyR2 by structurally defining direct binding to the ALK2 GS domain and to Glomulin, implicating it in TGF-β/BMP receptor regulation and FKBP-ligand-sensitive complexes.

    Evidence Co-IP and SEC-MALS with 2.17 Å ALK2-FKBP12.6 crystal structure; in vitro Glomulin binding versus FKBP12/51/52

    PMID:31490997 PMID:33572801

    Open questions at the time
    • Cellular consequences of ALK2 binding for BMP/TGF-β signaling not established
    • Glomulin interaction not yet linked to a downstream pathway
  22. 2020 High

    Defined a redox-driven dissociation mechanism in which RISP-dependent ROS during chronic hypoxia releases FKBP12.6 from RyR2 to drive NF-κB/cyclin D1 proliferation and pulmonary hypertension, providing a disease pathway with pharmacological rescue.

    Evidence SMC-specific RyR2 KO, RISP knockdown, FKBP12.6 KO, S107 stabilization, Co-IP, and Ca2+/NF-κB assays

    PMID:32669538

    Open questions at the time
    • Molecular target of ROS on the complex not pinpointed
    • Generalizability beyond pulmonary vasculature unknown
  23. 2018 High

    Showed FKBP12.6 restrains pathological cardiac hypertrophy by lowering intracellular Ca2+ and suppressing calcineurin/NFAT, CaMKII/MEF-2, and AKT/mTOR signaling, integrating its channel role into hypertrophic signaling.

    Evidence reciprocal FKBP12.6 KO and cardiac-specific transgenic mice with AngII infusion, echocardiography, Ca2+ imaging, and pathway immunoblots

    PMID:29682889

    Open questions at the time
    • Direct versus Ca2+-indirect contribution to each pathway not separated
    • Did not test rescue by RyR2 stabilization specifically
  24. 2025 Medium

    Identified post-translational control of FKBP12.6 abundance via NR3C1 repression of Glomulin, blocking FKBP12.6 ubiquitination so that stress-driven accumulation impairs mitochondrial quality control.

    Evidence ChIP-qPCR, NR3C1/GLMN siRNA knockdown, restraint-stress mouse models, electron microscopy, and Western blot

    PMID:40943170

    Open questions at the time
    • Single recent study with limited independent confirmation
    • Direct demonstration of Glomulin-mediated FKBP12.6 ubiquitination not shown
  25. 2026 Medium

    Extended FKBP12.6 regulation to a second channel class by showing direct IP3R binding in detrusor muscle and a knockout bladder-instability phenotype rescued by IP3R/TRPM4 inhibition.

    Evidence FKBP12.6 KO mice, Co-IP, urodynamic and void-spot testing, and pharmacological rescue with 2-APB/9-PHE

    PMID:40051354

    Open questions at the time
    • Single Co-IP without reciprocal structural mapping of the IP3R site
    • Selectivity versus RyR2 in this tissue not resolved
  26. 2015 Medium

    Placed FKBP1B within a miR-34a-regulated anti-adipogenic axis, indicating transcript-level control and a metabolic role distinct from Ca2+ channel regulation.

    Evidence luciferase 3'-UTR reporter, miR-34a mimic/inhibitor, and FKBP1B overexpression in 3T3-L1 adipogenesis assays

    PMID:26471303

    Open questions at the time
    • Mechanism by which FKBP1B suppresses PPARγ/C/EBPα undefined
    • Single cell-line context

Open questions

Synthesis pass · forward-looking unresolved questions
  • The physiological trigger and structural mechanism that dissociates FKBP12.6 from RyR2 under specific stress states, and how its newly identified partners (IP3R, ALK2, Glomulin) and PPIase activity integrate with channel regulation, remain to be unified.
  • No physiological PPIase substrate identified
  • N-terminal versus C-terminal RyR2 binding-site discrepancy unresolved
  • Conflicting knockout arrhythmia phenotypes not reconciled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0016853 isomerase activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-397014 Muscle contraction 3
Partners
ACVR1AKAP6GLMNITPR1PPP1CAPRKARRYR2
Complex memberships
RyR2-FKBP12.6-PKA-PP1-PP2A-mAKAP SR macromolecular complex

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 FKBP12.6 selectively binds to the cardiac ryanodine receptor (RyR2) but not to the skeletal muscle RyR1; only FKBP12.6 (not FKBP12) exchanges with endogenously bound FKBP12.6 or rebinds to FKBP-stripped cardiac sarcoplasmic reticulum, explaining why cardiac CRC is isolated as a complex with FKBP12.6. 35S-labeled FKBP12/12.6 binding assays, cosedimentation with stripped SR membranes The Journal of biological chemistry High 8702774
2000 FKBP12.6 is a component of a macromolecular complex on the sarcoplasmic reticulum comprising RyR2, FKBP12.6, PKA, phosphatases PP1 and PP2A, and the anchoring protein mAKAP, as defined by cosedimentation and co-immunoprecipitation. Cosedimentation, co-immunoprecipitation Cell High 10830164
2000 PKA phosphorylation of RyR2 dissociates FKBP12.6 from the channel complex and increases RyR2 open probability; in failing human hearts RyR2 is PKA hyperphosphorylated, resulting in FKBP12.6 dissociation and defective channel function. Co-immunoprecipitation, single-channel recordings, PKA phosphorylation assay, failing human heart tissue Cell Medium 10830164
2000 In canine pacing-induced heart failure, the stoichiometric ratio of FKBP12.6 per RyR monomer is significantly decreased (3.6 to 1.6) and FKBP12.6 protein expression is reduced, correlating with a prominent Ca2+ leak through RyR and conformational change in RyR. [3H]dihydro-FK506 and [3H]ryanodine binding assays, stopped-flow Ca2+ release measurements, Western blot Circulation High 11044432
2000 In heart failure, the number of FKBP12.6 binding sites (Bmax) on RyR is dramatically decreased (~83%) while affinity (Kd) is unchanged; this loss underlies RyR channel instability and impaired Ca2+ release function. [3H]dihydro-FK506 binding assay, stopped-flow Ca2+ release, FK506 competition Cardiovascular research High 11054478
2001 Adenoviral overexpression of FKBP12.6 in adult rabbit cardiomyocytes reduces SR Ca2+ leak through RyR2 by ~53%, increases SR Ca2+ load, and increases fractional shortening, demonstrating that FKBP12.6 stabilizes the closed conformation of RyR2. Adenovirus-mediated gene transfer, fluorometric Ca2+ uptake in permeabilized myocytes, contractility measurements Circulation research High 11157671
2002 FKBP12.6 disruption in mice results in cardiac hypertrophy in males but not females; both sexes show dysregulated Ca2+ release (increased Ca2+ spark amplitude and duration), indicating FKBP12.6 modulates cardiac excitation-contraction coupling. Estrogen receptor antagonism with tamoxifen causes hypertrophy in female knockouts. FKBP12.6 knockout mice, echocardiography, Ca2+ spark imaging (confocal), tamoxifen treatment Nature High 11907581
2002 FKBP12.6 binds to RyR2 and regulates type 2 RyRs in tracheal smooth muscle; cyclic ADP-ribose (cADPR) alters spontaneous and receptor-mediated Ca2+ release through FKBP12.6, as these effects are blocked by excess recombinant FKBP12.6 and absent in FKBP12.6-knockout mouse myocytes. FKBP12.6 knockout mice, intracellular cADPR dialysis, Ca2+ imaging, force measurement in isolated trachealis American journal of physiology. Cell physiology High 14592808
2002 cADPR activates RyR/Ca2+ release channels from coronary arterial smooth muscle SR through FKBP12.6; removal of FKBP12.6 by FK506 or anti-FKBP12 antibody completely abolishes cADPR-induced channel activation in planar lipid bilayer recordings. Planar lipid bilayer single-channel recording, FK506 dissociation, anti-FKBP12 antibody blockade, gradient centrifugation American journal of physiology. Heart and circulatory physiology High 11893565
2002 The FKBP12.6 binding site on RyR2 is localized to the NH2-terminal domain (residues 305–1937); deletion analyses show the first 305 residues and C-terminal residues 1937–4967 are not essential, while a fragment containing the first 1937 residues is sufficient for GST-FKBP12.6 binding. The isoleucine-proline dipeptide motif (I2427-P2428) is not the core binding site. GST pulldown with deletion mutants of RyR2 expressed in HEK293 cells The Journal of biological chemistry High 12446682
2003 FKBP12.6 co-expressed with human RyR2 in CHO cells is selectively recruited from cytoplasm to ER membranes (sequestration) as RyR2 expression increases; co-expression of FKBP12.6 (but not FKBP12) markedly decreases agonist-induced Ca2+ release and promotes ER Ca2+ superfilling, effects antagonized by rapamycin. Stable CHO cell lines expressing hRyR2, confocal microscopy, Ca2+ imaging, rapamycin competition The Biochemical journal High 12443530
2003 FKBP12.6 co-expression (but not FKBP12) in CHO cells expressing dysregulated hRyR2 suppresses intracellular Ca2+ flux and restores normal cell viability and proliferation; FKBP12.6's protective effect is independent of resting [Ca2+] or ER Ca2+ load. Stable CHO cell lines, Ca2+ imaging, cell viability/proliferation assays, ryanodine pharmacology The Journal of biological chemistry Medium 12754204
2003 FKBP12.6 deficiency in mice causes exercise-induced ventricular arrhythmias and sudden cardiac death; RyR2 mutations linked to CPVT reduce FKBP12.6 affinity for RyR2 and increase single-channel activity under simulated exercise conditions. FKBP12.6 knockout mice, in vivo exercise testing, single-channel recordings in lipid bilayers, radioligand binding Cell High 12837242
2004 PKA phosphorylation of RyR2 at serine-2808 does NOT dissociate FKBP12.6 from RyR2; both phosphorylated and non-phosphorylated forms of RyR2, as well as the S2808D phosphomimetic mutant, retain FKBP12.6 binding. Complete PKA phosphorylation does not disrupt native or recombinant FKBP12.6-RyR2 complex. Site-specific phosphorylation-state antibodies, Co-IP with recombinant and native RyR2, S2808D mutant binding assay Circulation research High 14715536
2004 The C-terminal domain of human RyR2 (encompassing pore-forming transmembrane domains) exhibits rapamycin-sensitive, specific binding to FKBP12.6 but not FKBP12 when expressed in mammalian cells, identifying a novel C-terminal FKBP12.6-binding site. Competition binding assays, mammalian cell expression of RyR2 C-terminal constructs, rapamycin competition The Journal of biological chemistry Medium 15591045
2004 FKBP12.6 overexpression in rat cardiac myocytes decreases Ca2+ spark amplitude, duration, width, and frequency, but enhances global [Ca2+]i transient amplitude and cell shortening, associated with increased SR Ca2+ load. Adenoviral overexpression, confocal Ca2+ spark imaging with Rhod-2, caffeine-evoked Ca2+ transients American journal of physiology. Heart and circulatory physiology Medium 15271664
2004 FKBP12.6 overexpression in adult rabbit cardiomyocytes increases peak-systolic [Ca2+], SR Ca2+ content, and synchronicity of SR Ca2+ release without altering L-type Ca2+ current or NCX; Ca2+ spark amplitude, duration, width, and frequency are reduced in permeabilized cells. Adenoviral overexpression, Fura-2/Fluo-3 Ca2+ imaging, voltage clamp, confocal microscopy The Journal of physiology Medium 14966299
2004 FKBP12.6 in pulmonary artery smooth muscle associates with RyR2 but not RyR1, RyR3, or IP3 receptors; FKBP12.6 deficiency enhances hypoxic and norepinephrine-induced Ca2+ release and vasoconstriction in pulmonary arterial smooth muscle cells. FKBP12.6 knockout mice, Ca2+ imaging, Ca2+-activated current measurements, FK506/rapamycin pharmacology, isolated tissue force measurements Cell calcium High 15036951
2005 Cryo-EM and 3D reconstruction localizes FKBP12.6 binding to the sides of the cytoplasmic region of canine RyR2 adjacent to domain 9 (clamp structures); FKBP12.6 binding alters RyR2 conformation particularly in the transmembrane region and clamp structures. Cryo-electron microscopy, 3D reconstruction, difference mapping, X-ray structure docking Biophysical journal High 16214874
2005 The central domain of human RyR2 does NOT mediate interaction with FKBP12.6; yeast two-hybrid and in vitro immunoprecipitation with overlapping fragments covering the entire RyR2 failed to reconstitute FKBP12.6 binding, and an alternatively spliced FKBP12.6 variant cannot interact with RyR. Yeast two-hybrid, in vitro immunoprecipitation, expression of overlapping RyR2 fragments Cell biochemistry and biophysics Medium 16049346
2005 FKBP12.6 (but not FKBP12) coexpression with cardiac DHPR (alpha1CYM) and RyR2 in dyspedic myotubes eliminates spontaneous Ca2+ oscillations and enables robust electrically evoked Ca2+ transients, demonstrating that FKBP12.6 suppresses spontaneous RyR2 activity and is required for ordered CICR. S2808D RyR2 phosphomimetic does not alter FKBP12.6 regulation in this reconstituted system. Reconstitution in RyR1-null dyspedic myotubes, Ca2+ imaging, electrical stimulation, FKBP12.6 coexpression with RyR2 S2808D mutant American journal of physiology. Cell physiology High 16049053
2006 Key aspartic acid residues on calstabin2/FKBP12.6 (particularly Asp-37) are involved in binding to RyR2 and in PKA phosphorylation-induced dissociation; a D37S mutant calstabin2 binds to the constitutively PKA-phosphorylated RyR2-S2808D mutant and restores normal cardiac function in a mouse model of heart failure. Site-directed mutagenesis of FKBP12.6, co-immunoprecipitation with RyR2-S2808D, in vivo myocardial infarction model with mutant calstabin2 manipulation Proceedings of the National Academy of Sciences of the United States of America High 16481613
2007 FKBP12.6 removal (by FK506 or genetic knockout) does NOT alter the conductance, Ca2+-activation, caffeine-activation, or subconductance state properties of recombinant or native RyR2, and FKBP12.6-null mice do not exhibit enhanced stress-induced ventricular arrhythmias. Single-channel lipid bilayer recordings, [3H]ryanodine binding, HEK293 SOICR imaging, FKBP12.6-null mouse stress testing The Journal of biological chemistry High 17921453
2007 K201 (JTV519) suppresses spontaneous Ca2+ release and inhibits [3H]ryanodine binding to RyR2 independently of FKBP12.6; FK506-induced dissociation of FKBP12.6 does not affect K201's suppression, and K201 is equally effective on RyR2 expressed with or without FKBP12.6. Rat ventricular myocytes, HEK293 cells expressing RyR2±FKBP12.6, FK506 pretreatment, [3H]ryanodine binding The Biochemical journal High 17313373
2008 FKBP12.6-deficient mice are highly susceptible to pacing-induced atrial fibrillation (81% vs 7% in WT); atrial myocytes from KO mice show 53% greater SR Ca2+ leak and increased spontaneous Ca2+ release events, both blocked by the RyR antagonist tetracaine. FKBP12.6-/- mice, intracardiac electrography, Ca2+ imaging in atrial myocytes, tetracaine pharmacology Heart rhythm High 18598963
2008 FKBP12.6 disruption impairs glucose-induced insulin secretion in pancreatic beta-cells; FKBP12.6-/- islets show markedly impaired glucose-stimulated Ca2+ elevation and insulin secretion (but normal sulfonylurea or KCl response), placing FKBP12.6 downstream of ATP production in the glucose-sensing pathway. FKBP12.6-/- mice generated by homologous recombination, in vivo glucose tolerance test, isolated islet insulin secretion assay, Ca2+ imaging Biochemical and biophysical research communications High 18466757
2009 Dissociation of FKBP12.6 from RyR2 does NOT play a significant role in beta-adrenergic-stimulated Ca2+ release; ISO increases Ca2+ spark frequency similarly in both WT and FKBP12.6 KO myocytes, and twitch force is not significantly different. In contrast, cADPR-stimulated Ca2+ spark augmentation occurs only in WT and not KO cells, placing cADPR action through FKBP12.6 dissociation from RyR2. FKBP12.6 KO mice, Ca2+ spark imaging, papillary muscle force measurements, pharmacological manipulation (thapsigargin, 2D12, cADPR) Cardiovascular research High 19578067
2009 FKBP12.6-/- mice display hyperinsulinemia and enhanced glucose-stimulated insulin secretion due to enhanced glucose-induced islet Ca2+ elevation; deletion also confers resistance to high-fat diet-induced hyperglycemia despite greater weight gain. FKBP12.6-/- mice, in vivo glucose tolerance test, ex vivo islet insulin secretion, Ca2+ imaging FASEB journal High 19805579
2000 Crystal structure of FKBP12.6 in complex with rapamycin determined at 2.0 Å resolution; FKBP12.6 and FKBP12 structures are nearly identical except for a displacement in the helical region of FKBP12.6 toward the hydrophobic pocket, not predicted by homology modeling. X-ray crystallography, 2.0 Å resolution Acta crystallographica. Section D, Biological crystallography High 10713512
2010 Direct fluorescent binding measurements in permeabilized myocytes show FKBP12.6 binds RyR2 with very high affinity (Kd ~0.7 nM) while FKBP12 has much lower affinity (Kd ~206 nM); only FKBP12.6 (not FKBP12) inhibits basal RyR2 activity; PKA phosphorylation does NOT alter binding kinetics or affinity of either FKBP for RyR2. Fluorescently labeled FKBP12.6/12 binding in permeabilized myocytes, FRAP, Ca2+ spark measurements, quantitative immunoblot Circulation research High 20431056
2011 Genetic inhibition of CaMKII phosphorylation of RyR2 at S2814 (S2814A mutation) prevents AF induction in FKBP12.6-/- mice by suppressing SR Ca2+ leak and DADs, while S2808A mutation does not protect; this epistasis places CaMKII-mediated RyR2-S2814 phosphorylation downstream of FKBP12.6 deficiency in the AF pathway. FKBP12.6-/-:S2814A double-mutant mice, intracardiac stimulation, Ca2+ spark/wave imaging, NCX current measurement Circulation research High 22158709
2012 FKBP12 is a high-affinity activator of RyR2 (sensitizes channel to cytosolic Ca2+), whereas FKBP12.6 has very low efficacy but can antagonize FKBP12 effects on single-channel gating; physiological concentrations of FKBP12 increase Ca2+ wave frequency and decrease SR Ca2+ content in cardiac cells. Single sheep RyR2 channels in planar phospholipid bilayers, Ca2+ wave measurements in permeabilized rat cardiomyocytes, mathematical modeling PloS one High 22363773
2002 VTSIP-associated RyR2 point mutations increase binding to FKBP12.6, while ARVD2-associated mutations decrease it, as measured by a quantitative yeast two-hybrid system; these opposing effects on FKBP12.6 binding correlate with the clinical differences between the two diseases. Quantitative yeast two-hybrid system with disease-associated RyR2 point mutations Biochemical and biophysical research communications Medium 12459180
2017 Cryo-EM structure of rabbit RyR2 in complex with FKBP12.6 at 11.8 Å resolution reveals that FKBP12.6 binding rigidifies the HD2 domain of RyR2 and stabilizes the closed state; two RyR2 conformations in the dataset are proposed to reflect phosphorylation state of the P2 domain. Cryo-electron microscopy, 3D reconstruction, atomic model building, conformational heterogeneity analysis Science signaling High 28536302
2016 Fully active FKBP12.6 (calstabin 2) retains peptidyl-prolyl cis-trans isomerase (PPIase) enzymatic activity; total chemical synthesis followed by refolding produced enzyme with catalytic activity and crystallographic structure (at 2.0 Å) indistinguishable from recombinant wild-type. Native chemical ligation synthesis, refolding, enzymatic activity assay, X-ray crystallography Protein science High 27670942
2013 Sirolimus (rapamycin) bound to FKBP12.6 impairs endothelial barrier function through RyR2-mediated intracellular Ca2+ elevation, protein kinase C-α activation, and disruption of the p120-VE cadherin interaction; siRNA knockdown of FKBP12.6 mimics these effects. HAEC culture, transendothelial electrical resistance, siRNA knockdown, Ca2+ imaging, PKC-α phosphorylation Western blot, immunostaining, mouse vascular permeability assay Arteriosclerosis, thrombosis, and vascular biology Medium 23887639
2017 Absence or inhibition of FKBP12.6 increases RyR2 sensitivity to L-type Ca2+ channel triggers (increased spark frequency and LCC-RyR coupling fidelity) without altering LCC open probability; this sensitization is additive with isoproterenol and can lead to chaotic Ca2+ waves and ventricular arrhythmias. FKBP12.6 KO mice, whole-cell patch clamp with confocal Ca2+ spark imaging, loose-seal patch-clamp LCC-RyR signaling kinetics, FK506/rapamycin pharmacology Cardiovascular research High 28077437
2018 FKBP12.6 protects against AngII-induced cardiac hypertrophy by reducing intracellular [Ca2+] and inhibiting calcineurin/NFATc4, CaMKII/MEF-2, AKT/GSK3β/NFATc4, and AKT/mTOR signaling pathways; KO aggravates and cardiac-specific TG overexpression prevents AngII-induced hypertrophy. FKBP12.6 KO and cardiac-specific TG mice, AngII osmotic pump infusion, echocardiography, Ca2+ imaging, Western blot for signaling pathway components Journal of cellular and molecular medicine High 29682889
2020 Rieske iron-sulfur protein (RISP)-dependent ROS generation causes dissociation of FKBP12.6 from RyR2 in pulmonary arterial smooth muscle cells during chronic hypoxia, leading to increased RyR2 activity, NF-κB/cyclin D1 activation, cell proliferation, and pulmonary hypertension; SMC-specific RyR2 KO, RISP knockdown, or RyR2/FKBP12.6 complex stabilization by S107 attenuates PH. SMC-specific RyR2 KO mice, RISP knockdown, FKBP12.6 KO, S107 pharmacological stabilization, co-IP, Ca2+ imaging, NF-κB/cyclin D1 activity assay Nature communications High 32669538
2021 FKBP12.6 directly binds BMP/TGF-β type I receptors (e.g., ALK2/ACVR1) but not type II receptors; the 2.17 Å crystal structure of the ALK2-FKBP12.6 complex shows FKBP12.6 binding to the GS domain of ALK2 in a manner equivalent to the FKBP12 complex, with ALK2 residues Phe198 and Leu199 inserting into the FK506-binding pocket. Cellular immunoprecipitation, SEC-MALS (1:1 direct interaction), X-ray crystallography at 2.17 Å Biomedicines High 33572801
2019 FKBP12.6 directly binds Glomulin (Glmn) in vitro with higher affinity than FKBP12; the FKBP51-Glmn interaction (as a model for the class) requires two amino acids lining the FK506-binding site and is blocked by FKBP ligands. In vitro binding assays (FKBP12.6 vs FKBP12 vs FKBP51/52 truncation mutants), FKBP ligand competition PloS one Medium 31490997
2009 FKBP12.6 overexpression in rabbit cardiomyocytes decreases inward rectifier current (IK1) amplitude by ~25% in a Ca2+-dependent and FK506-sensitive manner and prolongs action potential duration by ~30%; this effect is independent of calcineurin binding (shown using a calcineurin-binding deficient FKBP12.6 mutant). Adenoviral overexpression, whole-cell patch clamp, action potential recordings, FKBP12.6 calcineurin-binding mutant Pflugers Archiv : European journal of physiology Medium 19333617
2025 FKBP12.6 ubiquitination is regulated by NR3C1-mediated repression of Glomulin (GLMN); under stress, activated NR3C1 represses GLMN, preventing FKBP12.6 ubiquitination and degradation, leading to FKBP12.6 accumulation, calcium leakage/overload, and mitochondrial quality control impairment in cardiomyocytes. ChIP-qPCR, siRNA knockdown of NR3C1 and GLMN, mouse restraint stress models, transmission electron microscopy, Western blot International journal of molecular sciences Medium 40943170
2026 FKBP12.6 directly binds IP3R (inositol 1,4,5-trisphosphate receptor) in bladder detrusor muscle, as shown by co-immunoprecipitation; FKBP12.6 knockout increases bladder sensitivity and detrusor instability, and IP3R/TRPM4 pathway inhibitors rescue the knockout phenotype, indicating FKBP12.6 regulates bladder function through IP3R/TRPM4. FKBP12.6 KO mice, co-immunoprecipitation, urodynamic testing, void spot assay, pharmacological rescue with 2-APB and 9-PHE Current medicinal chemistry Medium 40051354
2015 miR-34a directly targets the 3'-UTR of FKBP1B mRNA to repress its expression; FKBP1B overexpression attenuates MDI-induced adipogenesis and reduces PPARγ and C/EBPα expression, demonstrating FKBP1B acts as an anti-adipogenic factor downstream of miR-34a. Luciferase 3'-UTR reporter assay, miR-34a mimic/inhibitor, FKBP1B overexpression in 3T3-L1 preadipocytes, adipogenesis assay Biochemical and biophysical research communications Medium 26471303
2014 X-ray crystal structures of unligated FKBP12.6 (1.70 and 1.90 Å) reveal conformational flexibility: the Phe59 active-site ring can rotate perpendicular to its typical orientation, and the '80s loop' peptide unit can flip; NMR shows 21 backbone amides undergo slow conformational exchange near the 80s loop. X-ray crystallography (two crystal forms), NMR backbone amide resonance doubling Acta crystallographica. Section D, Biological crystallography High 24598733
2012 Conditional deletion of the transcription factor CHF1/Hey2 in cardiomyocytes leads to increased FKBP12.6 expression; treatment with FK506 (which inhibits FKBP12.6-RyR2 association) restores contractile function in CHF1/Hey2 KO myocytes, placing FKBP12.6 downstream of CHF1/Hey2 in a pathway regulating cardiac EC coupling. Conditional KO mice, aortic banding, Ca2+ transients in isolated myocytes, gene expression analysis, FK506 pharmacological rescue American journal of physiology. Heart and circulatory physiology Medium 22408025
2009 FKBP12.6 overexpression conditionally in cardiac myocytes reduces Ca2+ spark frequency by 50% (including under isoproterenol) with unchanged SR Ca2+ load and prevents triggered ventricular tachycardia induced by burst pacing after isoproterenol pretreatment. Conditional cardiac-specific FKBP12.6 transgenic mice, in vivo electrophysiology, confocal Ca2+ spark imaging, Co-IP of FKBP12.6-RyR2 Circulation High 18378612

Source papers

Stage 0 corpus · 82 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell 1644 10830164
2003 FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Cell 613 12837242
2002 Oestrogen protects FKBP12.6 null mice from cardiac hypertrophy. Nature 245 11907581
1996 Selective binding of FKBP12.6 by the cardiac ryanodine receptor. The Journal of biological chemistry 220 8702774
2003 FKBP12.6-mediated stabilization of calcium-release channel (ryanodine receptor) as a novel therapeutic strategy against heart failure. Circulation 212 12551874
2000 Altered stoichiometry of FKBP12.6 versus ryanodine receptor as a cause of abnormal Ca(2+) leak through ryanodine receptor in heart failure. Circulation 189 11044432
2004 Protein kinase A phosphorylation at serine-2808 of the cardiac Ca2+-release channel (ryanodine receptor) does not dissociate 12.6-kDa FK506-binding protein (FKBP12.6). Circulation research 137 14715536
2011 Inhibition of CaMKII phosphorylation of RyR2 prevents induction of atrial fibrillation in FKBP12.6 knockout mice. Circulation research 134 22158709
2010 Kinetics of FKBP12.6 binding to ryanodine receptors in permeabilized cardiac myocytes and effects on Ca sparks. Circulation research 126 20431056
2001 Overexpression of FK506-binding protein FKBP12.6 in cardiomyocytes reduces ryanodine receptor-mediated Ca(2+) leak from the sarcoplasmic reticulum and increases contractility. Circulation research 124 11157671
2008 Intracellular calcium leak due to FKBP12.6 deficiency in mice facilitates the inducibility of atrial fibrillation. Heart rhythm 110 18598963
2003 FKBP12.6 and cADPR regulation of Ca2+ release in smooth muscle cells. American journal of physiology. Cell physiology 106 14592808
2002 Propranolol prevents the development of heart failure by restoring FKBP12.6-mediated stabilization of ryanodine receptor. Circulation 105 11901051
2002 Role of FKBP12.6 in cADPR-induced activation of reconstituted ryanodine receptors from arterial smooth muscle. American journal of physiology. Heart and circulatory physiology 93 11893565
2007 Removal of FKBP12.6 does not alter the conductance and activation of the cardiac ryanodine receptor or the susceptibility to stress-induced ventricular arrhythmias. The Journal of biological chemistry 87 17921453
2002 Localization of the 12.6-kDa FK506-binding protein (FKBP12.6) binding site to the NH2-terminal domain of the cardiac Ca2+ release channel (ryanodine receptor). The Journal of biological chemistry 80 12446682
2000 Altered interaction of FKBP12.6 with ryanodine receptor as a cause of abnormal Ca(2+) release in heart failure. Cardiovascular research 80 11054478
2007 K201 (JTV519) suppresses spontaneous Ca2+ release and [3H]ryanodine binding to RyR2 irrespective of FKBP12.6 association. The Biochemical journal 75 17313373
2006 Analysis of calstabin2 (FKBP12.6)-ryanodine receptor interactions: rescue of heart failure by calstabin2 in mice. Proceedings of the National Academy of Sciences of the United States of America 74 16481613
2004 FKBP12.6 overexpression decreases Ca2+ spark amplitude but enhances [Ca2+]i transient in rat cardiac myocytes. American journal of physiology. Heart and circulatory physiology 58 15271664
2012 FKBP12 activates the cardiac ryanodine receptor Ca2+-release channel and is antagonised by FKBP12.6. PloS one 56 22363773
2008 Conditional FKBP12.6 overexpression in mouse cardiac myocytes prevents triggered ventricular tachycardia through specific alterations in excitation-contraction coupling. Circulation 56 18378612
2013 Sirolimus-FKBP12.6 impairs endothelial barrier function through protein kinase C-α activation and disruption of the p120-vascular endothelial cadherin interaction. Arteriosclerosis, thrombosis, and vascular biology 52 23887639
2004 Over-expression of FK506-binding protein FKBP12.6 alters excitation-contraction coupling in adult rabbit cardiomyocytes. The Journal of physiology 49 14966299
2004 Interaction of FKBP12.6 with the cardiac ryanodine receptor C-terminal domain. The Journal of biological chemistry 49 15591045
2004 Role of FKBP12.6 in hypoxia- and norepinephrine-induced Ca2+ release and contraction in pulmonary artery myocytes. Cell calcium 46 15036951
2005 Three-dimensional visualization of FKBP12.6 binding to an open conformation of cardiac ryanodine receptor. Biophysical journal 45 16214874
2017 A cryo-EM-based model of phosphorylation- and FKBP12.6-mediated allosterism of the cardiac ryanodine receptor. Science signaling 40 28536302
2009 Dissociation of FKBP12.6 from ryanodine receptor type 2 is regulated by cyclic ADP-ribose but not beta-adrenergic stimulation in mouse cardiomyocytes. Cardiovascular research 40 19578067
2002 The binding of the RyR2 calcium channel to its gating protein FKBP12.6 is oppositely affected by ARVD2 and VTSIP mutations. Biochemical and biophysical research communications 40 12459180
2000 Structure of FKBP12.6 in complex with rapamycin. Acta crystallographica. Section D, Biological crystallography 40 10713512
2008 FKBP12.6 disruption impairs glucose-induced insulin secretion. Biochemical and biophysical research communications 37 18466757
2006 A novel endothelin receptor antagonist CPU0213 improves diabetic cardiac insufficiency attributed to up-regulation of the expression of FKBP12.6, SERCA2a, and PLB in rats. Journal of cardiovascular pharmacology 36 16810072
2003 Association of EDNRA, but not WNK4 or FKBP1B, polymorphisms with essential hypertension. Clinical genetics 35 14616768
2020 Rieske iron-sulfur protein induces FKBP12.6/RyR2 complex remodeling and subsequent pulmonary hypertension through NF-κB/cyclin D1 pathway. Nature communications 32 32669538
2003 In situ modulation of the human cardiac ryanodine receptor (hRyR2) by FKBP12.6. The Biochemical journal 32 12443530
2019 Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signaling. Drug design, development and therapy 28 31564830
2003 Dysregulated ryanodine receptors mediate cellular toxicity: restoration of normal phenotype by FKBP12.6. The Journal of biological chemistry 26 12754204
2007 Down-regulation of FKBP12.6 and SERCA2a contributes to acute heart failure in septic shock and is related to an up-regulated endothelin signalling pathway. The Journal of pharmacy and pharmacology 23 17637193
2008 Endothelin receptor antagonist CPU0213 and vitamin E reverse downregulation of FKBP12.6 and SERCA2a: a role of hyperphosphorylation of PKCepsilon. European journal of pharmacology 21 18611397
2008 Total triterpene acids, active ingredients from Fructus Corni, attenuate diabetic cardiomyopathy by normalizing ET pathway and expression of FKBP12.6 and SERCA2a in streptozotocin-rats. The Journal of pharmacy and pharmacology 21 19000375
2005 A novel mutation in FKBP12.6 binding region of the human cardiac ryanodine receptor gene (R2401H) in a Japanese patient with catecholaminergic polymorphic ventricular tachycardia. International journal of cardiology 21 15749201
2007 Reversal of isoproterenol-induced downregulation of phospholamban and FKBP12.6 by CPU0213-mediated antagonism of endothelin receptors. Acta pharmacologica Sinica 20 17959025
2007 Abrupt changes in FKBP12.6 and SERCA2a expression contribute to sudden occurrence of ventricular fibrillation on reperfusion and are prevented by CPU86017. Acta pharmacologica Sinica 18 17506935
2005 Central domain of the human cardiac muscle ryanodine receptor does not mediate interaction with FKBP12.6. Cell biochemistry and biophysics 18 16049346
2010 Limitations of FKBP12.6-directed treatment strategies for maladaptive cardiac remodeling and heart failure. Journal of molecular and cellular cardiology 17 20797399
2017 Sensitized signalling between L-type Ca2+ channels and ryanodine receptors in the absence or inhibition of FKBP12.6 in cardiomyocytes. Cardiovascular research 16 28077437
2009 FKBP12.6-knockout mice display hyperinsulinemia and resistance to high-fat diet-induced hyperglycemia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 19805579
2008 Downregulated FKBP12.6 expression and upregulated endothelin signaling contribute to elevated diastolic calcium and arrhythmogenesis in rat cardiomyopathy produced by l-thyroxin. International journal of cardiology 16 18684528
2020 Susceptibility to Ventricular Arrhythmias Resulting from Mutations in FKBP1B, PXDNL, and SCN9A Evaluated in hiPSC Cardiomyocytes. Stem cells international 14 32952569
2015 Shikonin inhibits adipogenic differentiation via regulation of mir-34a-FKBP1B. Biochemical and biophysical research communications 14 26471303
2011 Isoproterenol-induced FKBP12.6/12 downregulation is modulated by ETA and ETB receptors and reversed by argirhein, a derivative of rhein. Acta pharmacologica Sinica 13 21293474
2018 FKBP12.6 protects heart from AngII-induced hypertrophy through inhibiting Ca2+ /calmodulin-mediated signalling pathways in vivo and in vitro. Journal of cellular and molecular medicine 12 29682889
2013 Comparative differential proteomic profiles of nonfailing and failing hearts after in vivo thoracic aortic constriction in mice overexpressing FKBP12.6. Physiological reports 12 24303125
2012 Transcription factor CHF1/Hey2 regulates EC coupling and heart failure in mice through regulation of FKBP12.6. American journal of physiology. Heart and circulatory physiology 11 22408025
2012 Impact of hypoxia, simulated ischemia and reperfusion in HL-1 cells on the expression of FKBP12/FKBP12.6 and intracellular calcium dynamics. Biochemical and biophysical research communications 11 22618235
2016 Total chemical synthesis, refolding, and crystallographic structure of fully active immunophilin calstabin 2 (FKBP12.6). Protein science : a publication of the Protein Society 10 27670942
2011 Sildenafil and FDP-Sr attenuate diabetic cardiomyopathy by suppressing abnormal expression of myocardial CASQ2, FKBP12.6, and SERCA2a in rats. Acta pharmacologica Sinica 10 21441944
2009 FKBP12.6 binding of ryanodine receptors carrying mutations associated with arrhythmogenic cardiac disease. The Biochemical journal 10 19226252
2009 Stress-induced cardiac insufficiency relating to abnormal leptin and FKBP12.6 is ameliorated by CPU0213, an endothelin receptor antagonist, which is not affected by the CYP3A suppressing effect of erythromycin. The Journal of pharmacy and pharmacology 10 19405994
2005 Reconstitution of local Ca2+ signaling between cardiac L-type Ca2+ channels and ryanodine receptors: insights into regulation by FKBP12.6. American journal of physiology. Cell physiology 10 16049053
2015 Inhibition of the mevalonate pathway ameliorates anoxia-induced down-regulation of FKBP12.6 and intracellular calcium handling dysfunction in H9c2 cells. Journal of molecular and cellular cardiology 9 25636197
2011 Transgenic analysis of the role of FKBP12.6 in cardiac function and intracellular calcium release. Assay and drug development technologies 9 22087651
2019 Homologs of Human Dengue-Resistance Genes, FKBP1B and ATCAY, Confer Antiviral Resistance in Aedes aegypti Mosquitoes. Insects 7 30717390
2019 [Epigenetic Mechanisms of Peptide-Driven Regulation and Neuroprotective Protein FKBP1b]. Molekuliarnaia biologiia 6 31099784
2019 FKBP51 and FKBP12.6-Novel and tight interactors of Glomulin. PloS one 6 31490997
2011 FKBP12.6 mice display temporal gender differences in cardiac Ca(2+)-signalling phenotype upon chronic pressure overload. Canadian journal of physiology and pharmacology 6 22007848
2008 Adenovirus-mediated FKBP12.6 overexpression induces hypertrophy and apoptosis in cultured neonatal cardiomyocytes. Clinical and experimental pharmacology & physiology 6 18759859
2006 The inotropic adaptation during late preconditioning against myocardial stunning is associated with an increase in FKBP12.6. Cardiovascular research 6 17188666
2014 Crystal structure and conformational flexibility of the unligated FK506-binding protein FKBP12.6. Acta crystallographica. Section D, Biological crystallography 5 24598733
2012 FKBP12.6 overexpression does not protect against remodelling after myocardial infarction. Experimental physiology 5 22689442
2009 The effects of over-expression of the FK506-binding protein FKBP12.6 on K(+) currents in adult rabbit ventricular myocytes. Pflugers Archiv : European journal of physiology 5 19333617
2009 Myocardial release of FKBP12 and increased production of FKBP12.6 in ischemia and reperfusion experimental models. Biochemical and biophysical research communications 5 19878648
2021 ALK2 Receptor Kinase Association with FKBP12.6 Is Structurally Conserved with the ALK2-FKBP12 Complex. Biomedicines 3 33572801
2004 Evidence of association between FKBP1B and thyroid autoimmune disorders in a large Tunisian family. Autoimmunity 3 15497458
2010 CPU228, a derivative of dofetilide, relieves cardiac dysfunction by normalizing FKBP12.6, NADPH oxidase and protein kinase C epsilon in the myocardium. The Journal of pharmacy and pharmacology 2 20723002
2010 Altered expression and function of ryanodine receptors and FKBP12.6 after subarachnoid hemorrhage: more than meets the eye. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 2 20940731
2008 Decreased FKBP12.6 expression and enhanced endothelin receptor signaling associated with arrhymogenesis in myocardial infarction rats. Phytotherapy research : PTR 2 18570278
2022 Chai-Hu-San-Shen Capsule Ameliorates Ventricular Arrhythmia Through Inhibition of the CaMKII/FKBP12.6/RyR2/Ca2+ Signaling Pathway in Rats with Myocardial Ischemia. Evidence-based complementary and alternative medicine : eCAM 1 36225189
2026 Knockdown of FKBP12.6 may Cause Bladder Dysfunction in Mice by Affecting IP3R/TRPM4 Function. Current medicinal chemistry 0 40051354
2025 NR3C1/GLMN-Mediated FKBP12.6 Ubiquitination Disrupts Calcium Homeostasis and Impairs Mitochondrial Quality Control in Stress-Induced Myocardial Damage. International journal of molecular sciences 0 40943170
2001 [RyR-bound FKBP12.6 and the modulation]. Clinical calcium 0 15775577

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