Genomes and Genes
tacrolimus binding protein 1a
Summary: A 12-KDa tacrolimus binding protein that is found associated with and may modulate the function of calcium release channels. It is a peptidyl-prolyl cis/trans isomerase which is inhibited by both tacrolimus (commonly called FK506) and SIROLIMUS.
- Park S, Saven J. Statistical and molecular dynamics studies of buried waters in globular proteins. Proteins. 2005;60:450-63 pubmed
- Brath U, Akke M, Yang D, Kay L, Mulder F. Functional dynamics of human FKBP12 revealed by methyl 13C rotating frame relaxation dispersion NMR spectroscopy. J Am Chem Soc. 2006;128:5718-27 pubmed
- Oshiro N, Yoshino K, Hidayat S, Tokunaga C, Hara K, Eguchi S, et al. Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function. Genes Cells. 2004;9:359-66 pubmed
- Avila G, Lee E, Perez C, Allen P, Dirksen R. FKBP12 binding to RyR1 modulates excitation-contraction coupling in mouse skeletal myotubes. J Biol Chem. 2003;278:22600-8 pubmed..These data demonstrate that FKBP12 binding to RyR1 enhances the gain of skeletal muscle EC coupling. ..
- Somarelli J, Herrera R. Evolution of the 12 kDa FK506-binding protein gene. Biol Cell. 2007;99:311-21 pubmed publisher..Both structural and phylogenetics analyses suggest that the isoforms may be evolving independently, possibly due to the distinct functional roles played by each paralogue...
- Weiwad M, Edlich F, Kilka S, Erdmann F, Jarczowski F, Dorn M, et al. Comparative analysis of calcineurin inhibition by complexes of immunosuppressive drugs with human FK506 binding proteins. Biochemistry. 2006;45:15776-84 pubmed..Our results allow quantitative correlation between FK506-mediated CaN effects and the abundance of the different FKBPs in the cell. ..
- Liu F, Liu P, Shao H, Kung F. The intracellular domain of amyloid precursor protein interacts with FKBP12. Biochem Biophys Res Commun. 2006;350:472-7 pubmed..We also found that the interaction was interfered, in a dose-dependent manner, by FK506, whose neuroprotective effect has been suggested to be correlated with its PPIase inhibitory activity. ..
- Banaszynski L, Chen L, Maynard Smith L, Ooi A, Wandless T. A rapid, reversible, and tunable method to regulate protein function in living cells using synthetic small molecules. Cell. 2006;126:995-1004 pubmed..This general strategy for regulating protein stability should enable conditional perturbation of specific proteins with unprecedented control in a variety of experimental settings. ..
- Inomata K, Ohno A, Tochio H, Isogai S, Tenno T, Nakase I, et al. High-resolution multi-dimensional NMR spectroscopy of proteins in human cells. Nature. 2009;458:106-9 pubmed publisher..Moreover, in-cell NMR spectroscopy demonstrates that ubiquitin has much higher hydrogen exchange rates in the intracellular environment, possibly due to multiple interactions with endogenous proteins. ..
- Giordano A, Romano S, Mallardo M, D Angelillo A, Cali G, Corcione N, et al. FK506 can activate transforming growth factor-beta signalling in vascular smooth muscle cells and promote proliferation. Cardiovasc Res. 2008;79:519-26 pubmed publisher..Accordingly, cyclin D1 expression was increased. We also demonstrate that FK506 activates the TGF-beta signal in VSMCs and that, through this mechanism, it stimulates cell proliferation. FK506 can act as a growth factor for VSMCs. ..
- Weisman R. The fission yeast TOR proteins and the rapamycin response: an unexpected tale. Curr Top Microbiol Immunol. 2004;279:85-95 pubmed..pombe FKBP12 homologue. Why S. pombe cells are resistant to rapamycin during the growth phase is as yet unclear and awaits further analysis of the TOR-dependent signaling pathways. ..
- Mustafi S, Chen H, Li H, LeMaster D, HERNANDEZ G. Analysing the visible conformational substates of the FK506-binding protein FKBP12. Biochem J. 2013;453:371-80 pubmed publisher..The K44V mutation selectively reduces the line-broadening in the 40's loop, verifying that at least three distinct conformational transitions underlie the line-broadening processes of FKBP12. ..
- Samso M, Shen X, Allen P. Structural characterization of the RyR1-FKBP12 interaction. J Mol Biol. 2006;356:917-27 pubmed..The orientation of RyR1-bound FKBP12, with part of its FK506 binding site facing towards RyR1, allows us to propose how FK506 is involved in the dissociation of FKBP12 from RyR1. ..
- Gaburjakova M, Gaburjakova J, Reiken S, Huang F, Marx S, Rosemblit N, et al. FKBP12 binding modulates ryanodine receptor channel gating. J Biol Chem. 2001;276:16931-5 pubmed..6, an isoform of FKBP12. These data identify Val2461 as a critical residue required for FKBP12 binding to RyR1 and demonstrate the functional role for FKBP12 in the RyR1 channel complex. ..
- Lanner J, Georgiou D, Joshi A, Hamilton S. Ryanodine receptors: structure, expression, molecular details, and function in calcium release. Cold Spring Harb Perspect Biol. 2010;2:a003996 pubmed publisher..This chapter examines the current concepts of the structure, function and regulation of RyRs and assesses the current state of understanding of their roles in associated disorders. ..
- Chelu M, Danila C, Gilman C, Hamilton S. Regulation of ryanodine receptors by FK506 binding proteins. Trends Cardiovasc Med. 2004;14:227-34 pubmed..6 could play a role in heart failure, CPVT, and ARVD2. Also discussed are the consequences of FKBP12 depletion to skeletal muscle and the possibility of FKBP12 involvement in certain forms of MH or CCD. ..
- Bocciardi R, Bordo D, Di Duca M, Di Rocco M, Ravazzolo R. Mutational analysis of the ACVR1 gene in Italian patients affected with fibrodysplasia ossificans progressiva: confirmations and advancements. Eur J Hum Genet. 2009;17:311-8 pubmed publisher..The novel amino-acid substitution is predicted to influence either the conformation/stability of the GS region or the binding affinity with FKBP12, resulting in a less stringent inhibitory control on the ACVR1 kinase activity...
- 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...
- Loughrey C, Seidler T, Miller S, Prestle J, MacEachern K, Reynolds D, et al. Over-expression of FK506-binding protein FKBP12.6 alters excitation-contraction coupling in adult rabbit cardiomyocytes. J Physiol. 2004;556:919-34 pubmed..6 over-expression enhances Ca(2+) transient amplitude predominately by increasing SR Ca(2+) content. Moreover, there is also evidence that FKBP12.6 can enhance the coupling between SR Ca(2+) release sites independently of SR content. ..
- Higgins J, Montgomery K, Wang L, Domanay E, Warnke R, Brooks J, et al. Expression of FKBP12 in benign and malignant vascular endothelium: an immunohistochemical study on conventional sections and tissue microarrays. Am J Surg Pathol. 2003;27:58-64 pubmed..In addition, our findings may explain the toxic effects of FK506 on vascular endothelium of the kidney. ..
- MacMillan D, Currie S, McCarron J. FK506-binding protein (FKBP12) regulates ryanodine receptor-evoked Ca2+ release in colonic but not aortic smooth muscle. Cell Calcium. 2008;43:539-49 pubmed..Neither calcineurin nor mTOR are required for the FK506- or rapamycin-induced potentiation of RyR Ca(2+) release to occur. The results indicate that FKBP12 directly inhibits RyR channel activity in colonic myocytes but not in aorta. ..
- Varnai P, Thyagarajan B, Rohacs T, Balla T. Rapidly inducible changes in phosphatidylinositol 4,5-bisphosphate levels influence multiple regulatory functions of the lipid in intact living cells. J Cell Biol. 2006;175:377-82 pubmed
- Yazawa S, Obata K, Iio A, Koide M, Yokota M, Sasaki S, et al. Gene expression of FK506-binding proteins 12.6 and 12 during chicken development. Comp Biochem Physiol A Mol Integr Physiol. 2003;136:391-9 pubmed..These results suggest that, even though FKBP12.6 and FKBP12 genes are expressed in chick embryos, FK506-sensitive functions of the encoded proteins do not appear to contribute to early embryogenesis or cardiogenesis. ..
- Dargan S, Lea E, Dawson A. Modulation of type-1 Ins(1,4,5)P3 receptor channels by the FK506-binding protein, FKBP12. Biochem J. 2002;361:401-7 pubmed..These results provide evidence for a direct functional interaction between FKBP12 and the type-1 InsP(3)R. ..
- Sugata H, Matsuo K, Nakagawa T, Takahashi M, Mukai H, Ono Y, et al. A peptidyl-prolyl isomerase, FKBP12, accumulates in Alzheimer neurofibrillary tangles. Neurosci Lett. 2009;459:96-9 pubmed publisher..Thus our results suggest that FKBP12 may be involved in neuronal or astrocytic cytoskeletal organization and in the abnormal metabolism of tau protein in AD damaged neurons. ..
- Maynard Smith L, Chen L, Banaszynski L, Ooi A, Wandless T. A directed approach for engineering conditional protein stability using biologically silent small molecules. J Biol Chem. 2007;282:24866-72 pubmed..We then performed an unbiased microarray analysis of NIH3T3 cells treated with various concentrations of Shield-1. These studies show that Shield-1 does not elicit appreciable cellular responses. ..
- 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..Furthermore, using wild-type and genetically altered murine models of heart failure induced by myocardial infarction, we show that manipulating the stoichiometry between calstabin2 and RyR2 can restore normal cardiac function in vivo. ..
- Osman B, Doller A, Akool E, Holdener M, Hintermann E, Pfeilschifter J, et al. Rapamycin induces the TGFbeta1/Smad signaling cascade in renal mesangial cells upstream of mTOR. Cell Signal. 2009;21:1806-17 pubmed publisher..In conclusion, activation of the profibrotic TGFbeta/Smad signaling cascade accompanies the immunosuppressive and antiproliferative actions of rapamycin. ..
- Long C, Cook L, Wu G, Mitchell B. Removal of FKBP12/12.6 from endothelial ryanodine receptors leads to an intracellular calcium leak and endothelial dysfunction. Arterioscler Thromb Vasc Biol. 2007;27:1580-6 pubmed..Complete removal of FKBP12 and 12.6 from endothelial RyRs induces an intracellular Ca2+ leak which may contribute to the pathogenesis of endothelial dysfunction and hypertension caused by rapamycin or FK506. ..
- Crespo J, Díaz Troya S, Florencio F. Inhibition of target of rapamycin signaling by rapamycin in the unicellular green alga Chlamydomonas reinhardtii. Plant Physiol. 2005;139:1736-49 pubmed..Thus, our findings suggest that Chlamydomonas cell growth is positively controlled by a conserved TOR kinase and establish this unicellular alga as a useful model system for studying TOR signaling in photosynthetic eukaryotes. ..
- Tang W, Ingalls C, Durham W, Snider J, Reid M, Wu G, et al. Altered excitation-contraction coupling with skeletal muscle specific FKBP12 deficiency. FASEB J. 2004;18:1597-9 pubmed..In highly used muscles such as the diaphragm, adaptation to the loss of FKBP12 occurs, possibly due to the increased Ca2+ influx. ..
- Paulmurugan R, Massoud T, Huang J, Gambhir S. Molecular imaging of drug-modulated protein-protein interactions in living subjects. Cancer Res. 2004;64:2113-9 pubmed..Both are essential steps in the preclinical evaluation of candidate pharmaceutical agents targeting protein-protein interactions, including signaling pathways in cancer cells. ..
- Chaikuad A, Alfano I, Kerr G, Sanvitale C, Boergermann J, Triffitt J, et al. Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva. J Biol Chem. 2012;287:36990-8 pubmed publisher..The presented ALK2 structure offers a valuable template for the further design of specific inhibitors of BMP signaling. ..
- MacMillan D, Currie S, Bradley K, Muir T, McCarron J. In smooth muscle, FK506-binding protein modulates IP3 receptor-evoked Ca2+ release by mTOR and calcineurin. J Cell Sci. 2005;118:5443-51 pubmed..However, FKBP12 might indirectly modulate Ca2+ release through two effector proteins: (1) mTOR, which potentiates and (2) calcineurin, which inhibits Ca2+ release from IP3R in smooth muscle. ..
- Groppe J, Wu J, Shore E, Kaplan F. In vitro analyses of the dysregulated R206H ALK2 kinase-FKBP12 interaction associated with heterotopic ossification in FOP. Cells Tissues Organs. 2011;194:291-5 pubmed publisher..In conclusion, substitution with histidine leads to partial loss of inhibition of the mutant type I receptor through diminished binding of FKBP12, which may act as a gradient reader in morphogenetic contexts...
- 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. ..
- Blayney L, Jones J, Griffiths J, Lai F. A mechanism of ryanodine receptor modulation by FKBP12/12.6, protein kinase A, and K201. Cardiovasc Res. 2010;85:68-78 pubmed publisher..6 binding. K201 stabilized the conformation, whereas phosphorylation facilitated a subsequent molecular event that might increase the rate of an open/closed conformational transition...
- Mahfouz M, Kim S, Delauney A, Verma D. Arabidopsis TARGET OF RAPAMYCIN interacts with RAPTOR, which regulates the activity of S6 kinase in response to osmotic stress signals. Plant Cell. 2006;18:477-90 pubmed..Since homozygous mutation in TOR is lethal, it suggests that this pathway is essential for integrating the stress signals into the growth regulation. ..
- Maruyama M, Li B, Chen H, Xu X, Song L, Guatimosim S, et al. FKBP12 is a critical regulator of the heart rhythm and the cardiac voltage-gated sodium current in mice. Circ Res. 2011;108:1042-52 pubmed publisher..FKBP12 is a critical regulator of I(Na) and is important for cardiac arrhythmogenic physiology. FKPB12-mediated dysregulation of I(Na) may underlie clinical arrhythmias associated with FK506 administration. ..
- Reiken S, Lacampagne A, Zhou H, Kherani A, Lehnart S, Ward C, et al. PKA phosphorylation activates the calcium release channel (ryanodine receptor) in skeletal muscle: defective regulation in heart failure. J Cell Biol. 2003;160:919-28 pubmed..PKA hyperphosphorylation of RyR1 may contribute to impaired skeletal muscle function in HF, suggesting that a generalized EC coupling myopathy may play a role in HF. ..
- Fulton K, Jackson S, Buckle A. Energetic and structural analysis of the role of tryptophan 59 in FKBP12. Biochemistry. 2003;42:2364-72 pubmed..6 selectively binds the ryanodine receptor in cardiac muscle (RyR2). The structural response to mutation suggests that residue 59 contributes to the specificity of binding between FKBP12 isoforms and ryanodine receptors. ..
- Jeyakumar L, Ballester L, Cheng D, McIntyre J, Chang P, Olivey H, et al. FKBP binding characteristics of cardiac microsomes from diverse vertebrates. Biochem Biophys Res Commun. 2001;281:979-86 pubmed publisher..6. Dog is the exception. It can now be concluded that the association of FKBP isoforms with RyR2 is widely conserved in the hearts of different species of vertebrates...
- Veverka V, Crabbe T, Bird I, Lennie G, Muskett F, Taylor R, et al. Structural characterization of the interaction of mTOR with phosphatidic acid and a novel class of inhibitor: compelling evidence for a central role of the FRB domain in small molecule-mediated regulation of mTOR. Oncogene. 2008;27:585-95 pubmed
- Patursky Polischuk I, Stolovich Rain M, Hausner Hanochi M, Kasir J, Cybulski N, Avruch J, et al. The TSC-mTOR pathway mediates translational activation of TOP mRNAs by insulin largely in a raptor- or rictor-independent manner. Mol Cell Biol. 2009;29:640-9 pubmed publisher..This conclusion is further supported by the observation that raptor knockout renders the translation of TOP mRNAs rapamycin hypersensitive. ..
- O Reilly F, Robert M, Jona I, Szegedi C, Albrieux M, Geib S, et al. FKBP12 modulation of the binding of the skeletal ryanodine receptor onto the II-III loop of the dihydropyridine receptor. Biophys J. 2002;82:145-55 pubmed
- Kuramochi K, Miyano Y, Enomoto Y, Takeuchi R, Ishi K, Takakusagi Y, et al. Identification of small molecule binding molecules by affinity purification using a specific ligand immobilized on PEGA resin. Bioconjug Chem. 2008;19:2417-26 pubmed publisher..Our study suggests that PEGA resin has great potential as a tool not only for the purification and identification of small-molecule binding proteins but also for the selection of peptides that recognize target molecules. ..
- Jullien N, Goddard I, Selmi Ruby S, Fina J, Cremer H, Herman J. Conditional transgenesis using Dimerizable Cre (DiCre). PLoS ONE. 2007;2:e1355 pubmed..e. induce recombination at any desired time-point specifically in cells characterized by the simultaneous expression of two different promoters. ..
- 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. ..
- Chen Y, Smith M, Sheets M, Ballaron S, Trevillyan J, Burke S, et al. Zotarolimus, a novel sirolimus analogue with potent anti-proliferative activity on coronary smooth muscle cells and reduced potential for systemic immunosuppression. J Cardiovasc Pharmacol. 2007;49:228-35 pubmed..The pharmacological profile of zotarolimus suggests it may be advantageous for preventing restenosis with a reduced potential for causing systemic immunosuppression or other side effects. ..
- McPherson M, Yang Y, Hammond P, Kreider B. Drug receptor identification from multiple tissues using cellular-derived mRNA display libraries. Chem Biol. 2002;9:691-8 pubmed..Using this approach, it is anticipated that mRNA display could eventually play a key role in the discovery and characterization of new drug receptor interactions. ..
- Choi C, Li J, Vaal M, Thomas C, Limburg D, Wu Y, et al. Use of parallel-synthesis combinatorial libraries for rapid identification of potent FKBP12 inhibitors. Bioorg Med Chem Lett. 2002;12:1421-8 pubmed
- Rajan S, Saw K, Nguyen Q, Baek K, Yoon H. High-resolution crystal structure of FKBP12 from Aedes aegypti. Protein Sci. 2012;21:1080-4 pubmed publisher..Herein, we present a high-resolution crystal structure of AaFKBP12 at 1.3 Å resolution and discuss its structural features throwing light in facilitating the design of potential antagonists against the dengue-transmitting mosquito. ..
- Carmody M, Mackrill J, Sorrentino V, O NEILL C. FKBP12 associates tightly with the skeletal muscle type 1 ryanodine receptor, but not with other intracellular calcium release channels. FEBS Lett. 2001;505:97-102 pubmed..These results suggest that RyR1 has distinctive FKBP12 binding properties when compared to RyR2, RyR3, all IP(3)R isoforms and calcineurin. ..
- Shah M, Edman M, Janga S, Shi P, Dhandhukia J, Liu S, et al. A rapamycin-binding protein polymer nanoparticle shows potent therapeutic activity in suppressing autoimmune dacryoadenitis in a mouse model of Sjögren's syndrome. J Control Release. 2013;171:269-79 pubmed publisher..These findings suggest that FSI is a promising tool for delivering Rapa for treatment of SjS in a murine model and may be further explored to meet the unmet medical challenge of SjS. ..