Disease relevance of FKBP1B

• Two additional FCBP sequences in Flavobacterium and one in Treponema (spirochete) were also identified in which the CyP and FKBP domains were in the reverse order [1].
• In this study, the 28.3 kDa long type FKBP gene from a thermophilic archaeum, Methanobacterium thermoautotrophicum, was expressed in Escherichia coli, and its gene product (MbFK) was characterized [2].

High impact information on FKBP1B

• Microsequencing of peptide fragments from a cyanogen bromide digest of p78 identified this protein as BiP and sequence analysis identified p74 as the peptidyl-prolyl cis-trans isomerase, FKPB65 [3].
• Results from this study provide the first identification of a ligand for an FKBP in the secretory pathway and suggest that the prolyl cis-trans isomerase activity of FKBP65 may be important for the proper folding of the proline-rich tropoelastin molecule before secretion [3].
• Rapamycin, which binds specifically to FKBP12 binding protein, distributes evenly through the artery, whereas paclitaxel, which binds specifically to microtubules, remains primarily in the subintimal space [4].
• We report a novel group of dual-family immunophilins that contain both CyP and FKBP domains for which we propose the name FCBP (FK506- and cyclosporin-binding protein) [1].
• Prior to this report, all other FKBP family members had been irrelevant to the mechanism of action of FK-506 because no other FKBP.FK-506 complexes were able to bind and inhibit calcineurin [5].

Biological context of FKBP1B

• FK506 and rapamycin were also active antimalarials (IC50 of 1.9 and 2.6 microM, respectively) but in the absence of detectable FKBP in P. falciparum extracts, their mechanisms of antimalarial action remain unclear [6].
• The interaction of calcineurin (Ca2+/calmodulin-dependent protein phosphatase) with the potent immunosuppressive agent FK506 and its 12 kDa isoform binding protein (FKBP12) was investigated [7].
• Complete amino acid sequence of the FK506 and rapamycin binding protein, FKBP, isolated from calf thymus [8].
• Thus, naturally isolated bovine FKBP does not appear to have any residues modified by glycosylation, phosphorylation, or other posttranslational derivatization processes [8].
• Understanding the biological function of FKBP and other members of the immunophilin class and their respective complexes with immunosuppressive drugs may provide insights into cytoplasmic signalling mechanisms, protein folding and translocation, and other cellular processes [8].

Anatomical context of FKBP1B

• FKBP, an 11.8 kD intracellular protein that binds the immunosuppressants FK506 (Kd = 0.4 nM) and rapamycin (Kd = 0.2 nM) with high affinity, was purified to homogeneity from calf thymus [8].
• In this study, we identified a full-length cDNA sequence, vcCyP, encoding cyclophilin (CyP), a peptidyl-prolyl cis-trans isomerase of guard cell protoplasts (GCPs) from Vicia faba L [9].
• Therefore, FK506 inhibits Ca2+ mobilization in airway epithelium via FKBP but not calcineurin-dependent mechanism, which may result in the suppression of Ca2+-activated Cl- secretion [10].
• The characterization of a cyclophilin-type peptidyl prolyl cis-trans-isomerase from the endoplasmic-reticulum lumen [11].
• A luminally located peptidyl prolyl cis-trans-isomerase (PPI) has been purified from bovine liver microsomes [11].

Associations of FKBP1B with chemical compounds

• It was completely inhibited by concentrations of cyclosporin A above 0.1 microM, but not by FK506 or rapamycin, and probably represented one or more cyclophilins [6].
• [3H]FK506-FK506-binding protein (FKBP) complex does not bind polyethyleneimine-treated glass fiber filters, on the other hand, it binds the filter when it makes a complex with calcineurin [12].
• By Western blot analysis, arginine N-methyltransferase (PRMT1) and FK506 binding protein (FKBP) were detected in the SR used for reconstitution of RyR [13].
• These results suggest that protein methylation activates RyR/Ca(2+) release channels and may participate in the control of intracellular Ca(2+) mobilization in CASM cells by transferring a methyl group to the arginine moiety of the RyR accessory protein, FKBP 12 [13].

Physical interactions of FKBP1B

• These results suggest that calcineurin is a relevant cellular target of FK506 when bound to FKBP-12 [7].

Regulatory relationships of FKBP1B

• FK506 and FKBP-12 inhibited calcineurin in a concentration-dependent manner, and complete inhibition of the phosphatase activity appeared to require a molar excess of FKBP12-FK506 complex [7].

Other interactions of FKBP1B

• Roles of peptidyl-prolyl cis-trans isomerase and calcineurin in the mechanisms of antimalarial action of cyclosporin A, FK506, and rapamycin [6].
• The Pro1 residue of cyclolinopeptide A seems to play a fundamental role in determining the inhibition of the rotamase activity of cyclophilin A, as the homodetic analogue lacking this residue does not show any inhibitory ability [14].

Analytical, diagnostic and therapeutic context of FKBP1B

• To understand the structural basis of these findings, we have determined the three-dimensional structure of the complex of yeast FKBP12 with FK-506 by x-ray crystallography, and have found that the structure of the yeast complex is strikingly similar to its human homolog [15].
• We find, however, that the complex of yeast FKBP12 with L-685,818, a well characterized antagonist of FK-506 immunosuppression, is a potent inhibitor of calcineurin [15].
• The expression of a 12-kDa FKBP was greater in subconfluent cells than in confluent cells as determined by Western blotting, suggesting that the 12-kDa FKBP may be one of the factors that regulates Ca2+ oscillations [16].
• Immunocytochemistry revealed the existence of cytoplasmic FKBP-like immunoreactivities [16].

References