A rapamycin-selective 25-kDa immunophilin.
FKBP25, a previously uncharacterized 25-kDa FK506- and rapamycin-binding protein, was purified to homogeneity from calf thymus, brain, and spleen, and the sequence of a 215 amino acid (aa) 24-kDa C-terminal peptide was established. The N-terminal domain (101 aa) is unrelated to any known protein, is hydrophilic, and is predicted by circular dichroism spectroscopy to be largely alpha-helix. The C-terminal domain (114 aa) is homologous to FKBP12 and other FKBPs but has a potential nuclear targeting sequence and a unique insertion of seven amino acids in one of its loops. FKBP25 displays the rotamase activity characteristic of FKBPs; the activity is inhibited by the immunosuppressants rapamycin (Ki = 0.9 nM) and FK506 (Ki = 160 nM), but not cyclosporin A. The protein, its rapamycin selectivity, and the potential nuclear targeting sequence are discussed in terms of the structure of hFKBP12.
Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138.
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D000595:Amino Acid Sequence; D000818:Animals; D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001921:Brain; D002352:Carrier Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D002417:Cattle; D002942:Circular Dichroism; D003511:Cyclohexanols / Q000737:chemistry* / Q000494:pharmacology; D016208:Databases, Factual; D007166:Immunosuppressive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification; D011090:Polyenes / Q000302:isolation & purification / Q000494:pharmacology*; D011487:Protein Conformation; D011714:Pyrans / Q000737:chemistry* / Q000494:pharmacology; D016415:Sequence Alignment; D020123:Sirolimus; D013154:Spleen; D016559:Tacrolimus / Q000494:pharmacology; D013950:Thymus Gland
D000935:Antifungal Agents; D002352:Carrier Proteins; D003511:Cyclohexanols; D007166:Immunosuppressive Agents; D010455:Peptides; D011090:Polyenes; D011714:Pyrans; C066205:immunophilin ligand 506BD; D020123:Sirolimus; D016559:Tacrolimus