FKB1 encodes a nonessential FK 506-binding protein in Saccharomyces cerevisiae and contains regions suggesting homology to the cyclophilins.
FK 506, a powerful immunosuppressant that blocks allograft rejection by preventing T-cell activation, binds to an 11-kDa protein called the FK 506-binding protein (FKBP). Like cyclophilin, a cytosolic protein that binds another immunosuppressant, cyclosporin A, FKBP possesses peptidylprolyl cis-trans isomerase activity. We have isolated a genomic clone encoding the yeast FKBP (FKB1). The gene encodes a protein of 114 amino acids having a calculated Mr of 12,158. Disruption of the gene shows that FKB1 is not essential for growth. A search of translated nucleic acid data bases revealed bacterial FKBP homologs in Neisseria meningiditis and Pseudomonas aeruginosa. Comparison of the conserved amino acids in FKBP homologs with the conserved amino acids in the cyclophilins has revealed a region of similarity that we speculate to be a homologous domain related to the functional similarities of the two proteins.
Wiederrecht
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G
Merck Sharp & Dohme Research Laboratories, Rahway, NJ 07065.
Brizuela
L
L
Elliston
K
K
Sigal
N H
NH
Siekierka
J J
JJ
D000591:Amino Acid Isomerases / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003524:Cyclosporins / Q000378:metabolism; D015723:Gene Library; D005800:Genes, Fungal; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism*; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D019696:Peptidylprolyl Isomerase; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D016559:Tacrolimus; D022021:Tacrolimus Binding Proteins
D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D015345:Oligonucleotide Probes; D000591:Amino Acid Isomerases; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase; D016559:Tacrolimus