Genomes and Genes
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
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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...
- 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 publisherThe 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...
- 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..by 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...
- 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. ..
- 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...
- 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
- 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. ..
- 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 publisherb>Calstabin2 is a component of the cardiac ryanodine receptor (RyR2) macromolecular complex, which modulates Ca(2+) release from the sarcoplasmic reticulum in cardiomyocytes...
- 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. ..
- 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. ..
- 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...
- 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. ..
- 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
- 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...
- 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. ..
- 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. ..
- 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. ..