Genomes and Genes
Gene Symbol: Fkbp1b
Description: FK506 binding protein 1B
Alias: peptidyl-prolyl cis-trans isomerase FKBP1B, 12.6 kDa FK506-binding protein, 12.6 kDa FKBP, FKBP-12.6, FKBP-1B, PPIase FKBP1B, calstabin-2, immunophilin FKBP12.6, rotamase
- 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. ..
- 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. ..
- 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
- 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...
- He H, Yu F, Dai D, Dai Y. 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. J Pharm Pharmacol. 2007;59:977-84 pubmed..It is hypothesized that AHF is linked to down-regulation of FKBP12.6 (calstabin 2) and SERCA2a (sarco/endoplasmic reticulum Ca2+ ATPase 2a), which may be mediated by an activated endothelin (ET)..
- Gant J, Chen K, Kadish I, Blalock E, Thibault O, Porter N, et al. Reversal of Aging-Related Neuronal Ca2+ Dysregulation and Cognitive Impairment by Delivery of a Transgene Encoding FK506-Binding Protein 12.6/1b to the Hippocampus. J Neurosci. 2015;35:10878-87 pubmed publisher..Previously, we found that expression of the gene encoding FK506-binding protein 12.6/1b (FKBP1b), a small immunophilin that stabilizes RyR-mediated Ca2+ release in cardiomyocytes, declines in hippocampus of ..
- 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...
- Noguchi N, Takasawa S, Nata K, Tohgo A, Kato I, Ikehata F, et al. Cyclic ADP-ribose binds to FK506-binding protein 12.6 to release Ca2+ from islet microsomes. J Biol Chem. 1997;272:3133-6 pubmed..6 did not show Ca2+ release by cADPR. These results strongly suggest that cADPR may be the ligand for FKBP12.6 in islet RyR and that the binding of cADPR to FKBP12.6 frees the RyR from FKBP12.6, causing it to release Ca2+. ..
- Na T, Huang Z, Dai D, Zhang Y, Dai Y. Abrupt changes in FKBP12.6 and SERCA2a expression contribute to sudden occurrence of ventricular fibrillation on reperfusion and are prevented by CPU86017. Acta Pharmacol Sin. 2007;28:773-82 pubmed..Abrupt changes in the expression of FKBP12.6, SERCA2a, PKA, and ECE on reperfusion against ischemia, which are responsible for the rapid occurrence of VF, have been observed. These changes are effectively prevented by CPU86017. ..
- Zissimopoulos S, Thomas N, Jamaluddin W, Lai F. FKBP12.6 binding of ryanodine receptors carrying mutations associated with arrhythmogenic cardiac disease. Biochem J. 2009;419:273-8 pubmed publisher..6 binding, but to the same extent as for the wild-type. Our findings suggest that FKBP12.6 regulation of RyR2 is unlikely to be the primary defect in inherited arrhythmogenic cardiac disease...
- 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. ..
- 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, 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..TNF-?-induced caspase-8 activation leads to leaky RyR2 channels that contribute to myocardial remodeling after I/R. Thus, early prevention of SR Ca(2+) leak trough normalization of RyR2 function is cardioprotective. ..
- Gold B, Zeleny Pooley M, Chaturvedi P, Wang M. Oral administration of a nonimmunosuppressant FKBP-12 ligand speeds nerve regeneration. Neuroreport. 1998;9:553-8 pubmed..Orally active nonimmunosuppressant FKBP-12 ligands may be useful for the treatment of human peripheral nerve disorders. ..
- Li N, Jia N, Dai D, Dai Y. Endothelin receptor antagonist CPU0213 and vitamin E reverse downregulation of FKBP12.6 and SERCA2a: a role of hyperphosphorylation of PKCepsilon. Eur J Pharmacol. 2008;591:211-8 pubmed publisher..Thus by testing with biomarkers FKBP12.6 and SERCA2a, we have shown that the endothelin receptor antagonist CPU0213 and the antioxidant vitamin E may relieve risk of lethal arrhythmias and heart failure by suppressing PKCvarepsilon. ..
- Qi M, Liu H, Dai D, Li N, Dai Y. 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. J Pharm Pharmacol. 2008;60:1687-94 pubmed publisher..2 +/- 2.6 mmol L(-1)) in STZ-injected rats. Down-regulated expression of FKBP12.6 (calstabin 2), sarcoplasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) and phospholamban (PLB) were also found...
- 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..Normalization of the RyR2-mediated diastolic SR Ca(2+) leak prevents fatal sudden cardiac arrhythmias in DMD. ..
- Maalej A, Mbarki F, Rebai A, Karray F, Jouida J, Abid M, et al. Evidence of association between FKBP1B and thyroid autoimmune disorders in a large Tunisian family. Autoimmunity. 2004;37:237-9 pubmedb>FKBP1B belongs to immunophilins superfamily and functions as a cytosolic receptor protein of FK506. The role of FKBP1B in the immunosuppressive pathway of FK506 is well established...
- Du Y, Zhao J, Li X, Jin S, Ma W, Mu Q, et al. Dissociation of FK506-binding protein 12.6 kD from ryanodine receptor in bronchial smooth muscle cells in airway hyperresponsiveness in asthma. Am J Respir Cell Mol Biol. 2014;50:398-408 pubmed publisher..Dissociation of FKBP12.6 from RyR2 in BSMCs is responsible for the increased calcium response contributing to AHR in asthma. Manipulating the interaction of FKBP12.6 with RyR2 might be a novel and useful treatment for asthma. ..
- Gant J, Chen K, Norris C, Kadish I, Thibault O, Blalock E, et al. Disrupting function of FK506-binding protein 1b/12.6 induces the Ca²+-dysregulation aging phenotype in hippocampal neurons. J Neurosci. 2011;31:1693-703 pubmed publisher..In cardiomyocytes, FK506-binding protein 1b/12.6 (FKBP1b) binds and stabilizes RyR2 in the closed state, inhibiting RyR-mediated Ca(2+) release...
- Galfré E, Pitt S, Venturi E, Sitsapesan M, Zaccai N, Tsaneva Atanasova K, et al. FKBP12 activates the cardiac ryanodine receptor Ca2+-release channel and is antagonised by FKBP12.6. PLoS ONE. 2012;7:e31956 pubmed publisher..In heart failure, it is possible that an alteration in the dual regulation of RyR2 by FKBP12 and FKBP12.6 may occur. This could contribute towards a higher RyR2 open probability, 'leaky' RyR2 channels and Ca(2+)-dependent arrhythmias. ..