Mammalian Genome

, Volume 17, Issue 4, pp 322–331 | Cite as

The human FK506-binding proteins: characterization of human FKBP19

  • Stuart L. Rulten
  • Ross A. Kinloch
  • Hilda Tateossian
  • Colin Robinson
  • Lucy Gettins
  • John E. Kay
Article

Abstract

Analysis of the human repertoire of the FK506-binding protein (FKBP) family of peptidyl-prolyl cis/trans isomerases has identified an expansion of genes that code for human FKBPs in the secretory pathway. There are distinct differences in tissue distribution and expression levels of each variant. In this article we describe the characterization of human FKBP19 (Entrez Gene ID: FKBP11), an FK506-binding protein predominantly expressed in vertebrate secretory tissues. The FKBP19 sequence comprises a cleavable N-terminal signal sequence followed by a putative peptidyl-prolyl cis/trans isomerase domain with homology to FKBP12. This domain binds FK506 weakly in vitro. FKBP19 mRNA is abundant in human pancreas and other secretory tissues and high levels of FKBP19 protein are detected in the acinar cells of mouse pancreas.

References

  1. Arakawa H, Nagase H, Hayashi N, Fujiwara T, Ogawa M, et al. (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. Biochem Biophys Res Commun 200, 836–843CrossRefPubMedGoogle Scholar
  2. Baker EK, Colley NJ, Zuker C S (1994) The cyclophilin homolog NinaA functions as a chaperone, forming a stable complex in vivo with its protein target rhodopsin. EMBO J 13, 4886–4895PubMedGoogle Scholar
  3. Bush KT, Hendrickson BA, Nigam SK (1994) Induction of the FK506-binding protein, FKBP13, under conditions which misfold proteins in the endoplasmic reticulum. Biochem J 303, 705–708 [(1995) Erratum. Biochem J 305(Pt 3), 1031]PubMedGoogle Scholar
  4. Davis EC (2000) In Immunophilins in the Brain, B. Gold, G. Fischer, and T. Herdegen, eds. (Barcelona: Prous Science), Fk506-Binding proteins in the Secretory pathway. pp 59–66Google Scholar
  5. Fedorov AN, Baldwin TO (1997) Cotranslational protein folding. J Biol Chem 272, 32715–32718CrossRefPubMedGoogle Scholar
  6. Fischer G, Bang H, Mech C (1984) Detection of enzyme catalysis for cis-trans-isomerization of peptide-bonds using proline-containing peptides as substrates. Biomed Biochim Acta 43, 1101–1111PubMedGoogle Scholar
  7. Galat A (2003) Peptidyl prolyl cis/trans isomerases (immunophilins): biological diversity-targets-functions. Curr Top Med Chem 3, 1315–1347CrossRefPubMedGoogle Scholar
  8. Galat A, Riviere S (1998) Peptidyl-prolyl cis/trans isomerases. (Oxford: Oxford University Press)Google Scholar
  9. Goessling E, Kel-Margoulis OV, Kell AE, Wingender E (2001). MATCHTm- A tool for searching transcription factor binding sites in DNA sequences. Application for the analysis of human chromosomes. German Conference on Bioinformatics, Braunschweig, Germany (Oct 7–10, 2001)Google Scholar
  10. Horowitz DS, Kobayashi R, Krainer AR (1997) A new cyclophilin and the human homologues of yeast Prp3 and Prp4 form a complex associated with U4/U6 snRNPs. RNA 3, 1374–1387PubMedGoogle Scholar
  11. Ikeda Y, Schultz LW, Clardy J, Schreiber SL (1994) Structural basis for peptidomimicry by a natural product Journal of the American Chemical Society, 116, 4143–4144Google Scholar
  12. Inoue H, Nomiyama J, Nakai K, Matsutani A, Tanizawa Y, et al. (1998) Isolation of full-length cDNA of mouse PAX4 gene and identification of its human homologue. Biochem Biophys Res Commun 243, 628–633CrossRefPubMedGoogle Scholar
  13. Ishikawa K, Nagase T, Suyama M, Miyajima N, Tanaka A, et al. (1998) Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res 5, 169–176CrossRefPubMedGoogle Scholar
  14. Jin YJ, Albers MW, Lane WS, Bierer BE, Schreiber SL, et al. (1991) Molecular cloning of a membrane-associated human FK506- and rapamycin-binding protein, FKBP-13. Proc Natl Acad Sci U S A 88, 6677–6681PubMedGoogle Scholar
  15. Jin YJ, Burakoff SJ, Bierer BE (1992) Molecular cloning of a 25-kDa high affinity rapamycin binding protein, FKBP25. J Biol Chem 267: 10942–10945PubMedGoogle Scholar
  16. Kay JE (1996) Structure-function relationships in the FK506-binding protein (FKBP) family of peptidylprolyl cis-trans isomerases. Biochem J 314: 361–385PubMedGoogle Scholar
  17. Kay JE (2000) FKBP ligands: Novel Strategies for the Treatment of Neurodegenerative Disorders. In Immunophilins in the Brain, B. Gold, G. Fischer, T. Herdegen, eds., (Barcelona: Prous Science), pp 263– 268Google Scholar
  18. Kuzhandaivelu N, Cong YS, Inouye C, Yang WM, Seto E (1996) XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation. Nucleic Acids Res 24: 4741–4750CrossRefPubMedGoogle Scholar
  19. Lam E, Martin M, Wiederrecht G (1995) Isolation of a cDNA encoding a novel human FK506-binding protein homolog containing leucine zipper and tetratricopeptide repeat motifs. Gene 160: 297–302PubMedGoogle Scholar
  20. Meng X, Lu X, Morris CA, Keating MT (1998) A novel human gene FKBP6 is deleted in Williams syndrome. Genomics 52: 130–137CrossRefPubMedGoogle Scholar
  21. Michnick SW, Rosen MK, Wandless TJ, Karplus M, Schreiber SL (1991) Solution structure of FKBP, a rotamase enzyme and receptor for FK506 and rapamycin. Science 252: 836–839PubMedGoogle Scholar
  22. Munro S, Pelham HR (1987) A C-terminal signal prevents secretion of luminal ER proteins. Cell 48: 899–907CrossRefPubMedGoogle Scholar
  23. Nair SC, Rimerman RA, Toran EJ, Chen S, Prapapanich V, et al. (1997) Molecular cloning of human FKBP51 and comparisons of immunophilin interactions with Hsp90 and progesterone receptor. Mol Cell Biol 17: 594–603PubMedGoogle Scholar
  24. Nakai K, Horton P (1999) PSORT: a program for detecting sorting signals in proteins and predicting their subcellular localization. Trends Biochem Sci 24: 34–36CrossRefPubMedGoogle Scholar
  25. Nakamura T, Yabe D, Kanazawa N, Tashiro K, Sasayama S, et al. (1998) Molecular cloning, characterization, and chromosomal localization of FKBP23, a novel FK506-binding protein with Ca2+-binding ability. Genomics 54: 89–98CrossRefPubMedGoogle Scholar
  26. Pahl A, Brune K, Bang H (1997) Fit for life? Evolution of chaperones and folding catalysts parallels the development of complex organisms. Cell Stress Chaperones 2: 78–86CrossRefPubMedGoogle Scholar
  27. Patterson CE, Schaub T, Coleman EJ, Davis EC (2000) Developmental regulation of FKBP65. An ER-localized extracellular matrix binding-protein. Mol Biol Cell 11: 3925–3935PubMedGoogle Scholar
  28. Patterson CE, Gao J, Rooney AP, Davis EC (2002) Genomic organization of mouse and human 65 kDa FK506-binding protein genes and evolution of the FKBP multigene family. Genomics 79, 881–889CrossRefPubMedGoogle Scholar
  29. Peattie DA, Harding MW, Fleming MA, DeCenzo MT, Lippke JA, et al. (1992) Expression and characterization of human FKBP52, an immunophilin that associates with the 90-kDa heat shock protein and is a component of steroid receptor complexes. Proc Natl Acad Sci U S A 89, 10974–10978PubMedGoogle Scholar
  30. Pemberton TJ, Rulten SL, Kay JE (2003) Identification and characterization of Schizosaccharomyces pombe cyclophilin 3, a cyclosporin A insensitive orthologue of human USA-CyP. J Chromatogr B Analyt Technol Biomed Life Sci 786, 81–91PubMedGoogle Scholar
  31. Pennisi E (2003) Human genome. A low number wins the GeneSweep Pool. Science 300: 1484PubMedGoogle Scholar
  32. Ranganathan R, Lu KP, Hunter T, Noel JP (1997) Structural and functional analysis of the mitotic rotamase Pin1 suggests substrate recognition is phosphorylation dependent. Cell 89: 875–886CrossRefPubMedGoogle Scholar
  33. Ratajczak T, Carrello A (1996) Cyclophilin 40 (CyP-40), mapping of its hsp90 binding domain and evidence that FKBP52 competes with CyP-40 for hsp90 binding. J Biol Chem 271: 2961–2965PubMedGoogle Scholar
  34. Shadidy M, Caubit X, Olsen R, Seternes OM, Moens U, et al. (1999) Biochemical analysis of mouse FKBP60, a novel member of the FKPB family. Biochim Biophys Acta 1446: 295–307PubMedGoogle Scholar
  35. Siekierka JJ, Hung SH, Poe M, Lin CS, Sigal NH (1989) A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin. Nature 341: 755–757CrossRefPubMedGoogle Scholar
  36. Siekierka JJ, Wiederrecht G, Greulich H, Boulton D, Hung SH, et al. 1990) The cytosolic-binding protein for the immunosuppressant FK-506 is both a ubiquitous and highly conserved peptidyl-prolyl cis-trans isomerase. J Biol Chem 265: 21011–21015PubMedGoogle Scholar
  37. Standaert RF, Galat A, Verdine GL, Schreiber SL (1990) Molecular cloning and overexpression of the human FK506-binding protein FKBP. Nature 346: 671–674CrossRefPubMedGoogle Scholar
  38. Teasdale RD, Jackson MR (1996) Signal-mediated sorting of membrane proteins between the endoplasmic reticulum and the golgi apparatus. Annu Rev Cell Dev Biol 12: 27–54CrossRefPubMedGoogle Scholar
  39. Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22: 4673–4680PubMedGoogle Scholar
  40. von Heijne G (1983) Patterns of amino acids near signal-cleavage sites. Eur J Biochem 133: 17–21CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Stuart L. Rulten
    • 1
  • Ross A. Kinloch
    • 2
  • Hilda Tateossian
    • 3
  • Colin Robinson
    • 2
  • Lucy Gettins
    • 2
  • John E. Kay
    • 4
  1. 1.Trafford Centre for Graduate Medical Education and ResearchUniversity of SussexFalmerUK
  2. 2.Discovery Biology DepartmentPfizer Global Research and DevelopmentSandwichUK
  3. 3.MRC Mammalian Genetics UnitHarwellUK
  4. 4.Brighton and Sussex Medical SchoolFalmerUK

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