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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Feb 1;88(3):1029–1033. doi: 10.1073/pnas.88.3.1029

FKB1 encodes a nonessential FK 506-binding protein in Saccharomyces cerevisiae and contains regions suggesting homology to the cyclophilins.

G Wiederrecht 1, L Brizuela 1, K Elliston 1, N H Sigal 1, J J Siekierka 1
PMCID: PMC50948  PMID: 1704127

Abstract

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.

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Selected References

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  1. Bennetzen J. L., Hall B. D. Codon selection in yeast. J Biol Chem. 1982 Mar 25;257(6):3026–3031. [PubMed] [Google Scholar]
  2. Bergsma D. J., Sylvester D. A Chinese hamster ovary cyclophilin cDNA sequence. Nucleic Acids Res. 1990 Jan 11;18(1):200–200. doi: 10.1093/nar/18.1.200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bilofsky H. S., Burks C., Fickett J. W., Goad W. B., Lewitter F. I., Rindone W. P., Swindell C. D., Tung C. S. The GenBank genetic sequence databank. Nucleic Acids Res. 1986 Jan 10;14(1):1–4. doi: 10.1093/nar/14.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Danielson P. E., Forss-Petter S., Brow M. A., Calavetta L., Douglass J., Milner R. J., Sutcliffe J. G. p1B15: a cDNA clone of the rat mRNA encoding cyclophilin. DNA. 1988 May;7(4):261–267. doi: 10.1089/dna.1988.7.261. [DOI] [PubMed] [Google Scholar]
  5. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dobson M. J., Tuite M. F., Roberts N. A., Kingsman A. J., Kingsman S. M., Perkins R. E., Conroy S. C., Fothergill L. A. Conservation of high efficiency promoter sequences in Saccharomyces cerevisiae. Nucleic Acids Res. 1982 Apr 24;10(8):2625–2637. doi: 10.1093/nar/10.8.2625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fickett J. W. Recognition of protein coding regions in DNA sequences. Nucleic Acids Res. 1982 Sep 11;10(17):5303–5318. doi: 10.1093/nar/10.17.5303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fischer G., Wittmann-Liebold B., Lang K., Kiefhaber T., Schmid F. X. Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins. Nature. 1989 Feb 2;337(6206):476–478. doi: 10.1038/337476a0. [DOI] [PubMed] [Google Scholar]
  9. George D. G., Barker W. C., Hunt L. T. The protein identification resource (PIR). Nucleic Acids Res. 1986 Jan 10;14(1):11–15. doi: 10.1093/nar/14.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gribskov M., Burgess R. R. Sigma factors from E. coli, B. subtilis, phage SP01, and phage T4 are homologous proteins. Nucleic Acids Res. 1986 Aug 26;14(16):6745–6763. doi: 10.1093/nar/14.16.6745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Haendler B., Hofer-Warbinek R., Hofer E. Complementary DNA for human T-cell cyclophilin. EMBO J. 1987 Apr;6(4):947–950. doi: 10.1002/j.1460-2075.1987.tb04843.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Haendler B., Keller R., Hiestand P. C., Kocher H. P., Wegmann G., Movva N. R. Yeast cyclophilin: isolation and characterization of the protein, cDNA and gene. Gene. 1989 Nov 15;83(1):39–46. doi: 10.1016/0378-1119(89)90401-0. [DOI] [PubMed] [Google Scholar]
  13. Hamm G. H., Cameron G. N. The EMBL data library. Nucleic Acids Res. 1986 Jan 10;14(1):5–9. doi: 10.1093/nar/14.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Handschumacher R. E., Harding M. W., Rice J., Drugge R. J., Speicher D. W. Cyclophilin: a specific cytosolic binding protein for cyclosporin A. Science. 1984 Nov 2;226(4674):544–547. doi: 10.1126/science.6238408. [DOI] [PubMed] [Google Scholar]
  15. Harding M. W., Galat A., Uehling D. E., Schreiber S. L. A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl isomerase. Nature. 1989 Oct 26;341(6244):758–760. doi: 10.1038/341758a0. [DOI] [PubMed] [Google Scholar]
  16. Harding M. W., Handschumacher R. E., Speicher D. W. Isolation and amino acid sequence of cyclophilin. J Biol Chem. 1986 Jun 25;261(18):8547–8555. [PubMed] [Google Scholar]
  17. Harrison R. K., Stein R. L. Mechanistic studies of peptidyl prolyl cis-trans isomerase: evidence for catalysis by distortion. Biochemistry. 1990 Feb 20;29(7):1684–1689. doi: 10.1021/bi00459a003. [DOI] [PubMed] [Google Scholar]
  18. Harrison R. K., Stein R. L. Substrate specificities of the peptidyl prolyl cis-trans isomerase activities of cyclophilin and FK-506 binding protein: evidence for the existence of a family of distinct enzymes. Biochemistry. 1990 Apr 24;29(16):3813–3816. doi: 10.1021/bi00468a001. [DOI] [PubMed] [Google Scholar]
  19. Hein J. Unified approach to alignment and phylogenies. Methods Enzymol. 1990;183:626–645. doi: 10.1016/0076-6879(90)83041-7. [DOI] [PubMed] [Google Scholar]
  20. Higgins D. G., Sharp P. M. CLUSTAL: a package for performing multiple sequence alignment on a microcomputer. Gene. 1988 Dec 15;73(1):237–244. doi: 10.1016/0378-1119(88)90330-7. [DOI] [PubMed] [Google Scholar]
  21. Itoh N., Tanaka N., Mihashi S., Yamashina I. Molecular cloning and sequence analysis of cDNA for batroxobin, a thrombin-like snake venom enzyme. J Biol Chem. 1987 Mar 5;262(7):3132–3135. [PubMed] [Google Scholar]
  22. Kato J., Chu L., Kitano K., DeVault J. D., Kimbara K., Chakrabarty A. M., Misra T. K. Nucleotide sequence of a regulatory region controlling alginate synthesis in Pseudomonas aeruginosa: characterization of the algR2 gene. Gene. 1989 Dec 7;84(1):31–38. doi: 10.1016/0378-1119(89)90136-4. [DOI] [PubMed] [Google Scholar]
  23. Kino T., Hatanaka H., Miyata S., Inamura N., Nishiyama M., Yajima T., Goto T., Okuhara M., Kohsaka M., Aoki H. FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. J Antibiot (Tokyo) 1987 Sep;40(9):1256–1265. doi: 10.7164/antibiotics.40.1256. [DOI] [PubMed] [Google Scholar]
  24. Koletsky A. J., Harding M. W., Handschumacher R. E. Cyclophilin: distribution and variant properties in normal and neoplastic tissues. J Immunol. 1986 Aug 1;137(3):1054–1059. [PubMed] [Google Scholar]
  25. Lightowlers M. W., Haralambous A., Rickard M. D. Amino acid sequence homology between cyclophilin and a cDNA-cloned antigen of Echinococcus granulosus. Mol Biochem Parasitol. 1989 Oct;36(3):287–289. doi: 10.1016/0166-6851(89)90177-1. [DOI] [PubMed] [Google Scholar]
  26. Maki N., Sekiguchi F., Nishimaki J., Miwa K., Hayano T., Takahashi N., Suzuki M. Complementary DNA encoding the human T-cell FK506-binding protein, a peptidylprolyl cis-trans isomerase distinct from cyclophilin. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5440–5443. doi: 10.1073/pnas.87.14.5440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pearson W. R., Lipman D. J. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444–2448. doi: 10.1073/pnas.85.8.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Perry A. C., Nicolson I. J., Saunders J. R. Neisseria meningitidis C114 contains silent, truncated pilin genes that are homologous to Neisseria gonorrhoeae pil sequences. J Bacteriol. 1988 Apr;170(4):1691–1697. doi: 10.1128/jb.170.4.1691-1697.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rothstein R. J. One-step gene disruption in yeast. Methods Enzymol. 1983;101:202–211. doi: 10.1016/0076-6879(83)01015-0. [DOI] [PubMed] [Google Scholar]
  30. Schneuwly S., Shortridge R. D., Larrivee D. C., Ono T., Ozaki M., Pak W. L. Drosophila ninaA gene encodes an eye-specific cyclophilin (cyclosporine A binding protein). Proc Natl Acad Sci U S A. 1989 Jul;86(14):5390–5394. doi: 10.1073/pnas.86.14.5390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Siekierka J. J., Hung S. H., Poe M., Lin C. S., Sigal N. H. A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin. Nature. 1989 Oct 26;341(6244):755–757. doi: 10.1038/341755a0. [DOI] [PubMed] [Google Scholar]
  32. Siekierka J. J., Wiederrecht G., Greulich H., Boulton D., Hung S. H., Cryan J., Hodges P. J., Sigal N. H. The cytosolic-binding protein for the immunosuppressant FK-506 is both a ubiquitous and highly conserved peptidyl-prolyl cis-trans isomerase. J Biol Chem. 1990 Dec 5;265(34):21011–21015. [PubMed] [Google Scholar]
  33. Sigal N. H., Siekierka J. J., Dumont F. J. Observations on the mechanism of action of FK-506. A pharmacologic probe of lymphocyte signal transduction. Biochem Pharmacol. 1990 Nov 15;40(10):2201–2208. doi: 10.1016/0006-2952(90)90712-t. [DOI] [PubMed] [Google Scholar]
  34. Sikorski R. S., Hieter P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989 May;122(1):19–27. doi: 10.1093/genetics/122.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Standaert R. F., Galat A., Verdine G. L., Schreiber S. L. Molecular cloning and overexpression of the human FK506-binding protein FKBP. Nature. 1990 Aug 16;346(6285):671–674. doi: 10.1038/346671a0. [DOI] [PubMed] [Google Scholar]
  36. Takahashi N., Hayano T., Suzuki M. Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin. Nature. 1989 Feb 2;337(6206):473–475. doi: 10.1038/337473a0. [DOI] [PubMed] [Google Scholar]
  37. Tocci M. J., Matkovich D. A., Collier K. A., Kwok P., Dumont F., Lin S., Degudicibus S., Siekierka J. J., Chin J., Hutchinson N. I. The immunosuppressant FK506 selectively inhibits expression of early T cell activation genes. J Immunol. 1989 Jul 15;143(2):718–726. [PubMed] [Google Scholar]
  38. Tropschug M. Nucleotide sequence of the gene coding for cyclophilin/peptidyl-prolyl cis-trans isomerase of Neurospora crassa. Nucleic Acids Res. 1990 Jan 11;18(1):190–190. doi: 10.1093/nar/18.1.190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Tropschug M., Wachter E., Mayer S., Schönbrunner E. R., Schmid F. X. Isolation and sequence of an FK506-binding protein from N. crassa which catalyses protein folding. Nature. 1990 Aug 16;346(6285):674–677. doi: 10.1038/346674a0. [DOI] [PubMed] [Google Scholar]

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