Gene Symbol: Fkbp1b
Description: FK506 binding protein 1b
Alias: 12.6kDa, AW494148, FKBP12.6, calstabin2, peptidyl-prolyl cis-trans isomerase FKBP1B, 12.6 kDa FK506-binding protein, 12.6 kDa FKBP, FK506-binding protein 12.6, FK506-binding protein 1B, FKBP-12.6, FKBP-1B, PPIase FKBP1B, immunophilin FKBP12.6, rotamase
Species: mouse
Products:     Fkbp1b

Top Publications

  1. Datta P, Chytil A, Gorska A, Moses H. Identification of STRAP, a novel WD domain protein in transforming growth factor-beta signaling. J Biol Chem. 1998;273:34671-4 pubmed
    ..The existence of the STRAP gene from yeast to mammals indicates an evolutionarily conserved function in eukaryotes. The data suggest a potential role for STRAP in TGF-beta signal transduction. ..
  2. Xu X, Su B, Barndt R, Chen H, Xin H, Yan G, et al. FKBP12 is the only FK506 binding protein mediating T-cell inhibition by the immunosuppressant FK506. Transplantation. 2002;73:1835-8 pubmed
    ..We found that growth inhibition induced by FK506 is abolished in FKBP12-deficient cells but not in FKBP12.6-deficient cells. FKBP12 is the only FKBP family member that plays a key role in immunosuppressant-mediated immunosuppression. ..
  3. Xin H, Senbonmatsu T, Cheng D, Wang Y, Copello J, Ji G, et al. Oestrogen protects FKBP12.6 null mice from cardiac hypertrophy. Nature. 2002;416:334-8 pubmed
    ..We conclude that FKBP12.6 modulates cardiac excitation-contraction coupling and that oestrogen plays a protective role in the hypertrophic response of the heart to Ca2+ dysregulation. ..
  4. Wang Y, Zheng Y, Mei Q, Wang Q, Collier M, Fleischer S, et al. FKBP12.6 and cADPR regulation of Ca2+ release in smooth muscle cells. Am J Physiol Cell Physiol. 2004;286:C538-46 pubmed
    ..Taken together, these findings point to an important role of the FKBP12.6/RyR2 complex in stochastic (spontaneous) and receptor-mediated Ca2+ release in smooth muscle. ..
  5. Zhang X, Tallini Y, Chen Z, Gan L, Wei B, Doran R, et al. Dissociation of FKBP12.6 from ryanodine receptor type 2 is regulated by cyclic ADP-ribose but not beta-adrenergic stimulation in mouse cardiomyocytes. Cardiovasc Res. 2009;84:253-62 pubmed publisher
    ..6 affects Ca(2+) sparks and mediates the inotropic action of isoproterenol (ISO), and to investigate the underlying mechanisms of cyclic ADP-ribose (cADPR) regulation of Ca(2+) sparks...
  6. Huang F, Shan J, Reiken S, Wehrens X, Marks A. Analysis of calstabin2 (FKBP12.6)-ryanodine receptor interactions: rescue of heart failure by calstabin2 in mice. Proc Natl Acad Sci U S A. 2006;103:3456-61 pubmed
    ..RyR2, the predominant isoform in cardiac myocytes, comprises a macromolecular complex that includes calstabin2 (FKBP12.6). Calstabin2, an 11.8-kDa cis-trans peptidyl-prolyl isomerase (apparent molecular mass 12...
  7. Fauconnier J, Meli A, Thireau J, Roberge S, Shan J, Sassi Y, et al. Ryanodine receptor leak mediated by caspase-8 activation leads to left ventricular injury after myocardial ischemia-reperfusion. Proc Natl Acad Sci U S A. 2011;108:13258-63 pubmed publisher
    ..At 1 and 15 d after reperfusion, caspase-8 activation resulted in S-nitrosylation of the RyR2 and depletion of calstabin2 from the RyR2 complex, resulting in diastolic sarcoplasmic reticulum (SR) Ca(2+) leak...
  8. Shan J, Xie W, Betzenhauser M, Reiken S, Chen B, Wronska A, et al. Calcium leak through ryanodine receptors leads to atrial fibrillation in 3 mouse models of catecholaminergic polymorphic ventricular tachycardia. Circ Res. 2012;111:708-17 pubmed publisher
    ..b>Calstabin2 (FKBP12...
  9. Liu Y, Korte F, Moussavi Harami F, Yu M, Razumova M, Regnier M, et al. Transcription factor CHF1/Hey2 regulates EC coupling and heart failure in mice through regulation of FKBP12.6. Am J Physiol Heart Circ Physiol. 2012;302:H1860-70 pubmed publisher
    ..These findings demonstrate that conditional deletion of CHF1/Hey2 in the myocardium leads to abnormalities in calcium handling mediated by FKBP12.6 that predispose to pressure overload-induced heart failure. ..

Scientific Experts

More Information


  1. Li N, Wang T, Wang W, Cutler M, Wang Q, Voigt N, et al. Inhibition of CaMKII phosphorylation of RyR2 prevents induction of atrial fibrillation in FKBP12.6 knockout mice. Circ Res. 2012;110:465-70 pubmed publisher
    ..6-/- mice by suppressing SR Ca(2+) leak and DADs. These results suggest suppression of RyR2-S2814 phosphorylation as a potential anti-AF therapeutic target. ..
  2. Zhao Y, Guo Y, Gu L, Fan X, Yang H, Chen Z, et al. Sensitized signalling between L-type Ca2+ channels and ryanodine receptors in the absence or inhibition of FKBP12.6 in cardiomyocytes. Cardiovasc Res. 2017;113:332-342 pubmed publisher
    ..FKBP12.6 keeps the RyRs from over-sensitization, stabilizes the potentially regenerative CICR system, and thus may suppress the life-threatening arrhythmogenesis. ..
  3. Liao B, Zheng Y, Yadav V, Korde A, Wang Y. Hypoxia induces intracellular Ca2+ release by causing reactive oxygen species-mediated dissociation of FK506-binding protein 12.6 from ryanodine receptor 2 in pulmonary artery myocytes. Antioxid Redox Signal. 2011;14:37-47 pubmed publisher
    ..6 removal enhanced, whereas RyR2 gene deletion blocked the hypoxic increase in [Ca(2+)](i) in PASMCs. Collectively, we conclude that hypoxia may induce Ca(2+) release by causing ROS-mediated dissociation of FKBP12.6 from RyR2 in PASMCs. ..
  4. Liu Q, Zheng Y, Korde A, Li X, Ma J, Takeshima H, et al. Protein kinase C-epsilon regulates local calcium signaling in airway smooth muscle cells. Am J Respir Cell Mol Biol. 2009;40:663-71 pubmed publisher
    ..Taken together, these results indicate that PKCepsilon regulates Ca(2+) sparks by specifically interacting with RyR1, which plays an important role in the control of contractile responses in airway SMCs. ..
  5. Lehnart S, Wehrens X, Reiken S, Warrier S, Belevych A, Harvey R, et al. Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias. Cell. 2005;123:25-35 pubmed
    ..These data suggest that reduced PDE4D activity causes defective RyR2-channel function associated with heart failure and arrhythmias. ..
  6. Wehrens X, Lehnart S, Huang F, Vest J, Reiken S, Mohler P, et al. FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Cell. 2003;113:829-40 pubmed
    ..6 for RyR2 and increased single-channel activity under conditions that simulate exercise. These data suggest that "leaky" RyR2 channels can trigger fatal cardiac arrhythmias, providing a possible explanation for CPVT. ..
  7. Xiao J, Tian X, Jones P, Bolstad J, Kong H, Wang R, et al. Removal of FKBP12.6 does not alter the conductance and activation of the cardiac ryanodine receptor or the susceptibility to stress-induced ventricular arrhythmias. J Biol Chem. 2007;282:34828-38 pubmed
    ..Collectively, our results demonstrate that the loss of FKBP12.6 has no significant effect on the conduction and activation of RyR2 or the propensity for spontaneous Ca(2+) release and stress-induced ventricular arrhythmias. ..
  8. Astrom Olsson K, Li L, Olofsson C, Boren J, Ohlin H, Grip L. Impact of hypoxia, simulated ischemia and reperfusion in HL-1 cells on the expression of FKBP12/FKBP12.6 and intracellular calcium dynamics. Biochem Biophys Res Commun. 2012;422:732-8 pubmed publisher
    ..6, why this model may be suitable for further studies on ischemia and reperfusion with respect to calcium handling of the sarcoplasmic reticulum. ..
  9. Guo T, Cornea R, Huke S, Camors E, Yang Y, Picht E, et al. Kinetics of FKBP12.6 binding to ryanodine receptors in permeabilized cardiac myocytes and effects on Ca sparks. Circ Res. 2010;106:1743-52 pubmed publisher
    ..6-RyR2 association and activate RyR2. However, the function of FKBP12.6/12 and role of PKA phosphorylation in cardiac myocytes are controversial...
  10. Zissimopoulos S, Seifan S, Maxwell C, Williams A, Lai F. Disparities in the association of the ryanodine receptor and the FK506-binding proteins in mammalian heart. J Cell Sci. 2012;125:1759-69 pubmed publisher
    The FK506-binding proteins (FKBP12 and FKBP12.6; also known as FKBP1A and FKBP1B, respectively) are accessory subunits of the ryanodine receptor (RyR) Ca(2+) release channel. Aberrant RyR2-FKBP12...
  11. Liu X, Betzenhauser M, Reiken S, Meli A, Xie W, Chen B, et al. Role of leaky neuronal ryanodine receptors in stress-induced cognitive dysfunction. Cell. 2012;150:1055-67 pubmed publisher protein kinase A (PKA), oxidized, and nitrosylated, resulting in depletion of the stabilizing subunit calstabin2 (FKBP12.6) from the channel complex and intracellular calcium leak...
  12. Wang W, Landstrom A, Wang Q, Munro M, Beavers D, Ackerman M, et al. Reduced junctional Na+/Ca2+-exchanger activity contributes to sarcoplasmic reticulum Ca2+ leak in junctophilin-2-deficient mice. Am J Physiol Heart Circ Physiol. 2014;307:H1317-26 pubmed publisher
    ..This demonstrates two novel and independent cellular mechanisms by which JPH2 regulates RyR2-mediated SR Ca(2+) leak and heart failure development. ..
  13. Wehrens X, Lehnart S, Reiken S, Deng S, Vest J, Cervantes D, et al. Protection from cardiac arrhythmia through ryanodine receptor-stabilizing protein calstabin2. Science. 2004;304:292-6 pubmed
    ..and in patients with inherited forms of exercise-induced SCD, depletion of the channel-stabilizing protein calstabin2 (FKBP12...
  14. Ji G, Feldman M, Greene K, Sorrentino V, Xin H, Kotlikoff M. RYR2 proteins contribute to the formation of Ca(2+) sparks in smooth muscle. J Gen Physiol. 2004;123:377-86 pubmed
  15. Li B, Chen H, Maruyama M, Zhang W, Zhang J, Pan Z, et al. The role of FK506-binding proteins 12 and 12.6 in regulating cardiac function. Pediatr Cardiol. 2012;33:988-94 pubmed publisher
    ..Similar genetic approaches also confirm the role of FKBP12.6 in regulating cardiac ryanodine receptors. The current study demonstrated that FKBP12 and FKBP12.6 have very different physiologic functions in the heart. ..
  16. Yuan Q, Chen Z, Santulli G, Gu L, Yang Z, Yuan Z, et al. Functional role of Calstabin2 in age-related cardiac alterations. Sci Rep. 2014;4:7425 pubmed publisher
    b>Calstabin2 is a component of the cardiac ryanodine receptor (RyR2) macromolecular complex, which modulates Ca(2+) release from the sarcoplasmic reticulum in cardiomyocytes...
  17. Vinet L, Pezet M, Bito V, Briec F, Biesmans L, Rouet Benzineb P, et al. Cardiac FKBP12.6 overexpression protects against triggered ventricular tachycardia in pressure overloaded mouse hearts. Basic Res Cardiol. 2012;107:246 pubmed publisher
  18. Habib A, Karmali V, Polavarapu R, Akahori H, Cheng Q, Pachura K, et al. Sirolimus-FKBP12.6 impairs endothelial barrier function through protein kinase C-? activation and disruption of the p120-vascular endothelial cadherin interaction. Arterioscler Thromb Vasc Biol. 2013;33:2425-31 pubmed publisher
    ..These data suggest this mechanism may be an important contributor of SRL side effects related to impaired EBF. ..
  19. Chen Z, Li Z, Wei B, Yin W, Xu T, Kotlikoff M, et al. FKBP12.6-knockout mice display hyperinsulinemia and resistance to high-fat diet-induced hyperglycemia. FASEB J. 2010;24:357-63 pubmed publisher
    ..6 plays an important role in insulin secretion and blood glucose control, and raising the possibility that it may be a potential therapeutic target for the treatment of type 2 diabetes. ..
  20. Fauconnier J, Thireau J, Reiken S, Cassan C, Richard S, Matecki S, et al. Leaky RyR2 trigger ventricular arrhythmias in Duchenne muscular dystrophy. Proc Natl Acad Sci U S A. 2010;107:1559-64 pubmed publisher
    ..RyR2 from mdx hearts were S-nitrosylated and depleted of calstabin2 (FKBP12.6), resulting in "leaky" RyR2 channels and a diastolic SR Ca(2+) leak...
  21. Noguchi N, Yoshikawa T, Ikeda T, Takahashi I, Shervani N, Uruno A, et al. FKBP12.6 disruption impairs glucose-induced insulin secretion. Biochem Biophys Res Commun. 2008;371:735-40 pubmed publisher
    ..6(-/-) and wild-type islets. These results indicate that FKBP12.6 plays a role in glucose-induced insulin secretion downstream of ATP production, independently of ATP-sensitive K(+) channels, in pancreatic beta-cells. ..
  22. Bennett J, Clancy Y, McNeish J. Identification and characterization of the murine FK506 binding protein (FKBP) 12.6 gene. Mamm Genome. 1998;9:1069-71 pubmed
  23. Liu Y, Chen H, Ji G, Li B, Mohler P, Zhu Z, et al. Transgenic analysis of the role of FKBP12.6 in cardiac function and intracellular calcium release. Assay Drug Dev Technol. 2011;9:620-7 pubmed publisher
    ..MHC-FKBP12.6 mice displayed normal cardiac development and function. We demonstrated that MHC-FKBP12.6 mice are able to rescue abnormal cardiac hypertrophy and abnormal calcium release in FKBP12.6-deficient mice...
  24. Lehnart S, Terrenoire C, Reiken S, Wehrens X, Song L, Tillman E, et al. Stabilization of cardiac ryanodine receptor prevents intracellular calcium leak and arrhythmias. Proc Natl Acad Sci U S A. 2006;103:7906-10 pubmed
    ..Our data suggest that calstabin-2 deficiency is as a critical mediator of triggers that initiate cardiac arrhythmias. ..
  25. Dubois S, Shou W, Haneline L, Fleischer S, Waldmann T, Müller J. Distinct pathways involving the FK506-binding proteins 12 and 12.6 underlie IL-2-versus IL-15-mediated proliferation of T cells. Proc Natl Acad Sci U S A. 2003;100:14169-74 pubmed
    ..Thus, IL-15 induces T cell proliferation mainly via FKBP12-mediated p70S6K activation. In contrast, IL-2 signaling involves multiple pathways that include at least one additional pathway that depends on FKBP12.6. ..
  26. Sood S, Chelu M, van Oort R, Skapura D, Santonastasi M, Dobrev D, et al. Intracellular calcium leak due to FKBP12.6 deficiency in mice facilitates the inducibility of atrial fibrillation. Heart Rhythm. 2008;5:1047-54 pubmed publisher
    ..The increased vulnerability to AF in FKBP12.6-/- mice substantiates the notion that defective SR Ca(2+) release caused by abnormal RyR2 and FKBP12.6 interactions may contribute to the initiation or maintenance of atrial fibrillation. ..