Property Summary

NCBI Gene PubMed Count 34
PubMed Score 108.55
PubTator Score 84.76

Knowledge Summary


No data available



Accession P68106 Q13664 Q16645 Q53TM2 Q9BQ40 PPIase FKBP1B
Symbols OTK4


PANTHER Protein Class (1)


1C9H   3J8E   4C02   4IQ2   4IQC  

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

Protein-protein Interaction (4)

Gene RIF (20)

26009186 How phosphorylation of RyR affects channel activity and whether proteins such as the FK-506 binding proteins (FKBP12 and FKBP12.6) are involved in heart failure
26009182 RyRs have been identified as important targets of FKBP12 and FKBP12.6, members of the immunophilin family
23887639 Sirolimus-FKBP12.6 impairs endothelial barrier function by activation of protein kinase C-alpha and downstream disruption of the p120-VE cadherin interaction in vascular endothelium.
22236651 These data corroborate other studies suggesting that mutations in FKBP12 and FKBP12.6 genes are not commonly related to cardiac diseases.
22087651 FKBP12.6-deficient mice with cardiac hypertrophy do not display exercise-induced arrhythmia and/or sudden cardiac death.
20431056 Characterize the kinetics of FKBP12/12.6 binding to RyR2 in ventricular myocytes and effects on calcium signaling.
20404344 analysis of the ryanodine receptor FK506-binding protein subunit
19226252 The findings suggest that FKBP12.6 regulation of RyR2 is unlikely to be the primary defect in inherited arrhythmogenic cardiac disease.
17921453 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
17506935 Results describe abrupt changes in the expression of FKBP12.6, SERCA2a, PKA, and ECE on reperfusion against ischemia, which are responsible for the rapid occurrence of ventricular fibrillation, and their prevention by CPU86017.
17313373 Data show that K201 abolished spontaneous calcium release in cardiac myocytes, and that treating ventricular myocytes with FK506 to dissociate FKBP12.6 from ryanodine receptor RyR2 did not affect the suppression of spontaneous Ca2+ release by K201.
17200109 the redox state of the RyR is intimately connected with FKBP binding affinity.
15972811 Enhancing calstabin binding to ryanodine receptors improves cardiac and skeletal muscle function in heart failure.
15749201 FKBP12.6 plays a critical role in Ca channel gating, the R2401H mutation can be expected to alter Ca-induced Ca release and E-C coupling resulting in CPVT.
15591045 novel interaction site for FKBP12.6 may be present at the RyR2 C terminus, proximal to the channel pore, a sterically appropriate location that would enable this protein to play a central role in the modulation of this critical ion channel
15497458 FKBP1B gene is involved in the genetic susceptibility to the AITDs development in the studied family.
14616768 Observational study of gene-disease association. (HuGE Navigator)
12754204 data demonstrate that defective regulation of ryanodine receptor 2 causes altered cellular phenotype via profound perturbations in intracellular calcium signaling and highlight a key modulatory role of FK506 binding protein 12.6
12459180 Data show that VTSIP- and ARVD2-associated point mutations influence positively and negatively, respectively, the binding of RyR2 to its gating protein FKBP12.6.
12446682 localization of binding site to the NH2-terminal domain of the cardiac Ca2+ release channel

AA Sequence

QRAKLTCTPDVAYGATGHPGVIPPNATLIFDVELLNLE                                     71 - 108

Text Mined References (35)

PMID Year Title
26009186 2015 The ryanodine receptor provides high throughput Ca2+-release but is precisely regulated by networks of associated proteins: a focus on proteins relevant to phosphorylation.
26009182 2015 Bcl-2 and FKBP12 bind to IP3 and ryanodine receptors at overlapping sites: the complexity of protein-protein interactions for channel regulation.
25416956 2014 A proteome-scale map of the human interactome network.
23887639 2013 Sirolimus-FKBP12.6 impairs endothelial barrier function through protein kinase C-? activation and disruption of the p120-vascular endothelial cadherin interaction.
23233753 2013 In cardiomyocytes, binding of unzipping peptide activates ryanodine receptor 2 and reciprocally inhibits calmodulin binding.
22236651 2012 A negative screen for mutations in calstabin 1 and 2 genes in patients with dilated cardiomyopathy.
22087651 2011 Transgenic analysis of the role of FKBP12.6 in cardiac function and intracellular calcium release.
20431056 2010 Kinetics of FKBP12.6 binding to ryanodine receptors in permeabilized cardiac myocytes and effects on Ca sparks.
20404344 2010 Mapping the ryanodine receptor FK506-binding protein subunit using fluorescence resonance energy transfer.
19226252 2009 FKBP12.6 binding of ryanodine receptors carrying mutations associated with arrhythmogenic cardiac disease.
19197348 2009 Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae.
17921453 2007 Removal of FKBP12.6 does not alter the conductance and activation of the cardiac ryanodine receptor or the susceptibility to stress-induced ventricular arrhythmias.
17506935 2007 Abrupt changes in FKBP12.6 and SERCA2a expression contribute to sudden occurrence of ventricular fibrillation on reperfusion and are prevented by CPU86017.
17313373 2007 K201 (JTV519) suppresses spontaneous Ca2+ release and [3H]ryanodine binding to RyR2 irrespective of FKBP12.6 association.
17200109 2007 Redox sensitivity of the ryanodine receptor interaction with FK506-binding protein.
16122887 2005 Genomic organization, chromosomal localization, and promoter of human gene for FK506-binding protein 12.6.
15972811 2005 Enhancing calstabin binding to ryanodine receptors improves cardiac and skeletal muscle function in heart failure.
15815621 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
15749201 2005 A novel mutation in FKBP12.6 binding region of the human cardiac ryanodine receptor gene (R2401H) in a Japanese patient with catecholaminergic polymorphic ventricular tachycardia.
15591045 2005 Interaction of FKBP12.6 with the cardiac ryanodine receptor C-terminal domain.
15497458 2004 Evidence of association between FKBP1B and thyroid autoimmune disorders in a large Tunisian family.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14616768 2003 Association of EDNRA, but not WNK4 or FKBP1B, polymorphisms with essential hypertension.
12754204 2003 Dysregulated ryanodine receptors mediate cellular toxicity: restoration of normal phenotype by FKBP12.6.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12459180 2002 The binding of the RyR2 calcium channel to its gating protein FKBP12.6 is oppositely affected by ARVD2 and VTSIP mutations.
12446682 2003 Localization of the 12.6-kDa FK506-binding protein (FKBP12.6) binding site to the NH2-terminal domain of the cardiac Ca2+ release channel (ryanodine receptor).
12443530 2003 In situ modulation of the human cardiac ryanodine receptor (hRyR2) by FKBP12.6.
11322937 2001 Receptor accessory folding helper enzymes: the functional role of peptidyl prolyl cis/trans isomerases.
11237759 2001 FKBP binding characteristics of cardiac microsomes from diverse vertebrates.
10830164 2000 PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts.
10713512 2000 Structure of FKBP12.6 in complex with rapamycin.
9013543 1997 Cyclic ADP-ribose binds to FK506-binding protein 12.6 to release Ca2+ from islet microsomes.
7592869 1995 A novel FK506 binding protein can mediate the immunosuppressive effects of FK506 and is associated with the cardiac ryanodine receptor.
7513996 1994 Molecular cloning and expression of a novel human gene that is highly homologous to human FK506-binding protein 12kDa (hFKBP-12) and characterization of two alternatively spliced transcripts.