Fkbp1a

Summary

Gene Symbol: Fkbp1a
Description: FK506 binding protein 1a
Alias: FKBP12, Fkbp, Fkbp1, peptidyl-prolyl cis-trans isomerase FKBP1A, FK506 binding protein 12, PPIase FKBP1A, calstabin-1, immunophilin FKBP12
Species: mouse
Products:     Fkbp1a

Top Publications

  1. Cook L, Chiasson V, Long C, Wu G, Mitchell B. Tacrolimus reduces nitric oxide synthase function by binding to FKBP rather than by its calcineurin effect. Kidney Int. 2009;75:719-26 pubmed publisher
    ..Since it is known that the FK506 binding protein (FKBP12/12...
  2. Bellinger A, Reiken S, Dura M, Murphy P, Deng S, Landry D, et al. Remodeling of ryanodine receptor complex causes "leaky" channels: a molecular mechanism for decreased exercise capacity. Proc Natl Acad Sci U S A. 2008;105:2198-202 pubmed publisher
    ..S-nitrosylated, and depleted of the phosphodiesterase PDE4D3 and the RyR1 stabilizing subunit calstabin1 (FKBP12), resulting in "leaky" channels that cause decreased exercise tolerance in mice...
  3. 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
    The immunophilin FKBP12 binds the skeletal muscle Ca2+ release channel or ryanodine receptor (RyR1), but the functional consequences of this interaction are not known...
  4. 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
    ..Its role in regulating postnatal cardiac function remains largely unknown. We generated FKBP12 overexpressing transgenic (?MyHC-FKBP12) mice and cardiomyocyte-restricted FKBP12 conditional knockout (FKBP12(f/f)..
  5. Siamakpour Reihani S, CASTER J, Bandhu Nepal D, Courtwright A, Hilliard E, Usary J, et al. The role of calcineurin/NFAT in SFRP2 induced angiogenesis--a rationale for breast cancer treatment with the calcineurin inhibitor tacrolimus. PLoS ONE. 2011;6:e20412 pubmed publisher
    Tacrolimus (FK506) is an immunosuppressive drug that binds to the immunophilin FKBPB12. The FK506-FKBP12 complex associates with calcineurin and inhibits its phosphatase activity, resulting in inhibition of nuclear translocation of ..
  6. Shin D, Pan Z, Bandyopadhyay A, Bhat M, Kim D, Ma J. Ca(2+)-dependent interaction between FKBP12 and calcineurin regulates activity of the Ca(2+) release channel in skeletal muscle. Biophys J. 2002;83:2539-49 pubmed
    ..This association involves a Ca(2+) dependent interaction between calcineurin and FK506-binding protein (FKBP12), an accessory subunit of RyR...
  7. Boortz K, Syring K, Lee R, Dai C, Oeser J, McGuinness O, et al. G6PC2 Modulates the Effects of Dexamethasone on Fasting Blood Glucose and Glucose Tolerance. Endocrinology. 2016;157:4133-4145 pubmed
    ..These observations demonstrate that G6pc2 modulates the complex effects of Dex on both FBG and glucose tolerance. ..
  8. 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
  9. Andersson D, Betzenhauser M, Reiken S, Meli A, Umanskaya A, Xie W, et al. Ryanodine receptor oxidation causes intracellular calcium leak and muscle weakness in aging. Cell Metab. 2011;14:196-207 pubmed publisher
    ..Taken together, these data indicate that leaky RyR1 contributes to age-related loss of muscle function...

Scientific Experts

More Information

Publications43

  1. Bellinger A, Reiken S, Carlson C, Mongillo M, Liu X, Rothman L, et al. Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle. Nat Med. 2009;15:325-30 pubmed publisher
    ..RyR1 S-nitrosylation depleted the channel complex of FKBP12 (also known as calstabin-1, for calcium channel stabilizing binding protein), resulting in 'leaky' channels...
  2. Corona B, Rouviere C, Hamilton S, Ingalls C. FKBP12 deficiency reduces strength deficits after eccentric contraction-induced muscle injury. J Appl Physiol (1985). 2008;105:527-37 pubmed publisher
    ..b>FKBP12 is a 12-kDa binding protein known to bind to the skeletal muscle sarcoplasmic reticulum Ca2+ release channel [..
  3. Jacinto E, Loewith R, Schmidt A, Lin S, Ruegg M, Hall A, et al. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol. 2004;6:1122-8 pubmed
    ..mTORC2 is not upstream of the mTORC1 effector S6K. Thus, two distinct TOR complexes constitute a primordial signalling network conserved in eukaryotic evolution to control the fundamental process of cell growth. ..
  4. 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
    Specifically, FK506-binding proteins 12 (FKBP12) and 12.6 (FKBP12.6) are cis-trans peptidyl prolyl isomerases that are expressed in the heart. Both FKBP12 and FKBP12...
  5. 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. ..
  6. Maiarù M, Tochiki K, Cox M, Annan L, Bell C, Feng X, et al. The stress regulator FKBP51 drives chronic pain by modulating spinal glucocorticoid signaling. Sci Transl Med. 2016;8:325ra19 pubmed publisher
    ..Thus, FKBP51 is a central mediator of chronic pain, likely in humans as well as rodents, and is a new pharmacologically tractable target for the treatment of long-term pain states. ..
  7. Poon M, Marx S, Gallo R, Badimon J, Taubman M, Marks A. Rapamycin inhibits vascular smooth muscle cell migration. J Clin Invest. 1996;98:2277-83 pubmed
    ..0001). Thus, in addition to being a potent immunosuppressant and antiproliferative, rapamycin also inhibits SMC migration. ..
  8. Nelson P, Lippke J, Murcko M, Rosborough S, Peattie D. cDNA encoding murine FK506-binding protein (FKBP): nucleotide and deduced amino acid sequence. Gene. 1991;109:255-8 pubmed
    A FKBP cDNA encoding murine FK506 binding protein (FKBP) has been cloned, and its complete nucleotide sequence has been determined...
  9. 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
    ..muscle sarcoplasmic reticulum (SR) Ca2+ release channel or ryanodine receptor (RyR1) binds four molecules of FKBP12, and the interaction of FKBP12 with RyR1 regulates both unitary and coupled gating of the channel...
  10. 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...
  11. 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
    ..In contrast to FKBP12-/- cells, splenic FKBP12...
  12. Fong S, Mounkes L, Liu Y, Maibaum M, Alonzo E, Desprez P, et al. Functional identification of distinct sets of antitumor activities mediated by the FKBP gene family. Proc Natl Acad Sci U S A. 2003;100:14253-8 pubmed
    ..in tumor-bearing mice to identify novel antiinvasive and antimetastatic functions for Fkbp8, and subsequently for Fkbp1a. Fkbp8 is a previously uncharacterized member of the FK-506-binding protein (FKBP) gene family down-regulated in ..
  13. Chiasson V, Talreja D, Young K, Chatterjee P, Banes Berceli A, Mitchell B. FK506 binding protein 12 deficiency in endothelial and hematopoietic cells decreases regulatory T cells and causes hypertension. Hypertension. 2011;57:1167-75 pubmed publisher
    Patients treated with the immunosuppressive drug tacrolimus (FK506), which binds FK506 binding protein 12 (FKBP12) and then inhibits the calcium-dependent phosphatase calcineurin, exhibit decreased regulatory T cells, endothelial ..
  14. Colucci S, Pagani A, Pettinato M, Artuso I, Nai A, Camaschella C, et al. The immunophilin FKBP12 inhibits hepcidin expression by binding the BMP type I receptor ALK2 in hepatocytes. Blood. 2017;130:2111-2120 pubmed publisher
    ..in response to iron and inflammation and among drugs, by rapamycin, which inhibits mTOR in complex with the immunophilin FKBP12. FKBP12 interacts with BMP type I receptors to avoid uncontrolled signaling...
  15. Paterson J, Smith S, Harmar A, Antoni F. Control of a novel adenylyl cyclase by calcineurin. Biochem Biophys Res Commun. 1995;214:1000-8 pubmed
    The molecular complex formed by the immunosuppressant FK506 and the immunophilin protein FKBP12 potently inhibits the Ca2+/calmodulin-activated protein phosphatase calcineurin...
  16. Hoeffer C, Tang W, Wong H, Santillan A, Patterson R, Martinez L, et al. Removal of FKBP12 enhances mTOR-Raptor interactions, LTP, memory, and perseverative/repetitive behavior. Neuron. 2008;60:832-45 pubmed publisher
    FK506-binding protein 12 (FKBP12) binds the immunosuppressant drugs FK506 and rapamycin and regulates several signaling pathways, including mammalian target of rapamycin (mTOR) signaling...
  17. 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
    ..model investigate the impact of simulated ischemia and reperfusion on expression of the calcium handling proteins FKBP12 and FKBP12.6, and intracellular calcium dynamics...
  18. Hendrickson B, Zhang W, Craig R, Jin Y, Bierer B, Burakoff S, et al. Structural organization of the genes encoding human and murine FK506-binding protein (FKBP) 13 and comparison to FKBP1. Gene. 1993;134:271-5 pubmed
    ..b>FKBP12 and FKBP13 are encoded by distinct genes, designated FKBP1 and FKBP2, respectively...
  19. Nilsson A, Sköld K, Sjögren B, Svensson M, Pierson J, Zhang X, et al. Increased striatal mRNA and protein levels of the immunophilin FKBP-12 in experimental Parkinson's disease and identification of FKBP-12-binding proteins. J Proteome Res. 2007;6:3952-61 pubmed
    b>FKBP-12, a 12 kDa FK506-binding protein (neuroimmunophilin), acts as a receptor for the immunosuppressant drug FK506...
  20. Stankunas K, Bayle J, Havranek J, Wandless T, Baker D, Crabtree G, et al. Rescue of degradation-prone mutants of the FK506-rapamycin binding (FRB) protein with chemical ligands. Chembiochem. 2007;8:1162-9 pubmed
    ..Because rapamycin is capable of simultaneously binding both FRB and the chaperone, FK506-binding protein (FKBP), we next examined whether FKBP might contribute to the protection of FRB mutants...
  21. 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
    ..Several FKBP family members such as FKBP12, FKBP12.6, and FKBP51 are expressed in T cells...
  22. Chiasson V, Jones K, Kopriva S, Mahajan A, Young K, Mitchell B. Endothelial cell transforming growth factor-? receptor activation causes tacrolimus-induced renal arteriolar hyalinosis. Kidney Int. 2012;82:857-66 pubmed publisher
    ..transforming growth factor (TGF)-? levels, tacrolimus inhibits calcineurin by binding to FK506-binding protein 12 (FKBP12). FKBP12 alone also inhibits TGF-? receptor activation...
  23. Galic M, Jeong S, Tsai F, Joubert L, Wu Y, Hahn K, et al. External push and internal pull forces recruit curvature-sensing N-BAR domain proteins to the plasma membrane. Nat Cell Biol. 2012;14:874-81 pubmed publisher
    ..Together, our results show that N-BAR domains can be directly recruited to the plasma membrane by external push or internal pull forces that locally curve the plasma membrane. ..
  24. 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...
  25. Marks A. Intracellular calcium-release channels: regulators of cell life and death. Am J Physiol. 1997;272:H597-605 pubmed
    ..structures of RyR1 and RyR2 are stabilized by a channel-associated protein known as the FK506 binding protein (FKBP)...
  26. 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...
  27. Marks A. Cellular functions of immunophilins. Physiol Rev. 1996;76:631-49 pubmed
    ..the absence of immunosuppressive ligands, is the modulation of intracellular calcium release channel function by FKBP12 and FKBP12.6...
  28. 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
    ..Here we show that FK506 binding protein of 12.6 kDa (FKBP12.6) associates with and regulates type 2 RyRs (RyR2) in tracheal smooth muscle. FKBP12...
  29. Eltit J, Feng W, Lopez J, Padilla I, Pessah I, Molinski T, et al. Ablation of skeletal muscle triadin impairs FKBP12/RyR1 channel interactions essential for maintaining resting cytoplasmic Ca2+. J Biol Chem. 2010;285:38453-62 pubmed publisher
    ..Accordingly, pulldown analysis and fluorescent FKBP12 binding studies in triadin-null muscles revealed a significant impairment of the FKBP12/RyR1 interaction...
  30. 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
    The 12.6-kDa FK506-binding protein (FKBP12.6) is considered to be a key regulator of the cardiac ryanodine receptor (RyR2), but its precise role in RyR2 function is complex and controversial...
  31. 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
    FK506 binding proteins 12 and 12.6 (FKBP12 and FKBP12.6) are intracellular receptors for the immunosuppressant drug FK506 (ref. 1). The skeletal muscle ryanodine receptor (RyR1) is isolated as a hetero-oligomer with FKBP12 (ref...
  32. Chen H, Zhang W, Sun X, Yoshimoto M, Chen Z, Zhu W, et al. Fkbp1a controls ventricular myocardium trabeculation and compaction by regulating endocardial Notch1 activity. Development. 2013;140:1946-57 pubmed publisher
    ..Fkbp1a (FKBP12) is a ubiquitously expressed cis-trans peptidyl-prolyl isomerase...
  33. Lee C, Georgiou D, Dagnino Acosta A, Xu J, Ismailov I, Knoblauch M, et al. Ligands for FKBP12 increase Ca2+ influx and protein synthesis to improve skeletal muscle function. J Biol Chem. 2014;289:25556-70 pubmed publisher
    ..Similar changes are found with SLF (synthetic ligand for FKBP12, which does not inhibit mTORC1) and in mice with a skeletal muscle-specific FKBP12 deficiency...
  34. Shou W, Aghdasi B, Armstrong D, Guo Q, Bao S, Charng M, et al. Cardiac defects and altered ryanodine receptor function in mice lacking FKBP12. Nature. 1998;391:489-92 pubmed
    b>FKBP12, a cis-trans prolyl isomerase that binds the immunosuppressants FK506 and rapamycin, is ubiquitously expressed and interacts with proteins in several intracellular signal transduction systems...