Biochemical analysis of mouse FKBP60, a novel member of the FKPB family.

We have identified mouse and human FKBP60, a new member of the FKBP gene family. FKBP60 shares strongest homology with FKBP65 and SMAP. FKBP60 contains a hydrophobic signal peptide at the N-terminus, 4 peptidyl-prolyl cis/trans isomerase (PPIase) domains and an endoplasmic reticulum retention motif (HDEL) at the C-terminus. Immunodetection of HA-tagged FKBP60 in NIH-3T3 cells suggests that FKBP60 is segregated to the endoplasmic reticulum. Northern blot analysis shows that FKBP60 is predominantly expressed in heart, skeletal muscle, lung, liver and kidney. With N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide as a substrate, recombinant GST-FKBP60 is shown to accelerate effectively the isomerization of the peptidyl-prolyl bond. This isomerization activity is inhibited by FK506. mFKBP60 binds Ca2+ in vitro, presumably by its C-terminal EF-hand Ca2+ binding motif, and is phosphorylated in vivo. hFKBP60 has been mapped to 7p12 and/or 7p14 by fluorescence in situ hybridization (FISH).

[1]  S. Snyder,et al.  Immunophilin FK506 binding protein associated with inositol 1,4,5-trisphosphate receptor modulates calcium flux. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[2]  A. Marks,et al.  Stabilization of calcium release channel (ryanodine receptor) function by FK506-binding protein , 1994, Cell.

[3]  M. Matzuk,et al.  Cardiac defects and altered ryanodine receptor function in mice lacking FKBP12 , 1998, Nature.

[4]  J. Lippke,et al.  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. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[5]  S. Schreiber,et al.  Immunophilin-ligand complexes as probes of intracellular signaling pathways. , 1991, Transplantation proceedings.

[6]  S. Ebashi,et al.  Detection of calcium binding proteins by 45Ca autoradiography on nitrocellulose membrane after sodium dodecyl sulfate gel electrophoresis. , 1984, Journal of biochemistry.

[7]  S. Burakoff,et al.  The 25-kDa FK506-binding protein is localized in the nucleus and associates with casein kinase II and nucleolin. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[8]  E. Baulieu,et al.  Rabbit FKBP59-heat shock protein binding immunophillin (HBI) is a calmodulin binding protein. , 1992, Biochemical and biophysical research communications.

[9]  M. Saier,et al.  Structural and evolutionary relationships among the immunophilins: two ubiquitous families of peptidyl‐prolyl cis‐trans isomerases , 1992, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[10]  S. Nigam,et al.  Induction of the FK506-binding protein, FKBP13, under conditions which misfold proteins in the endoplasmic reticulum. , 1994, The Biochemical journal.

[11]  A. Dilella,et al.  Exon organization of the human FKBP-12 gene: correlation with structural and functional protein domains. , 1991, Biochemistry.

[12]  L. Kay,et al.  Correlation between dynamics and high affinity binding in an SH2 domain interaction. , 1996, Biochemistry.

[13]  T. Yokota,et al.  Xenopus FK 506-binding protein homolog induces a secondary axis in frog embryos, which is inhibited by coexisting BMP 4 signaling. , 1997, Biochemical and biophysical research communications.

[14]  S. Yasugi,et al.  cFKBP/SMAP; a novel molecule involved in the regulation of smooth muscle differentiation. , 1998, Development.

[15]  T. Starzl,et al.  Liver transplantation. , 1989, The Johns Hopkins medical journal.

[16]  S. Snyder,et al.  Calcineurin associated with the inositol 1,4,5-trisphosphate receptor-FKBP12 complex modulates Ca2+ flux , 1995, Cell.

[17]  P. Donahoe,et al.  The Immunophilin FKBP12 Functions as a Common Inhibitor of the TGFβ Family Type I Receptors , 1996, Cell.

[18]  X. Wang,et al.  MAPKAPK5, a novel mitogen-activated protein kinase (MAPK)-activated protein kinase, is a substrate of the extracellular-regulated kinase (ERK) and p38 kinase. , 1998, Biochemical and biophysical research communications.

[19]  M. Martin,et al.  FKBP51, a novel T-cell-specific immunophilin capable of calcineurin inhibition , 1995, Molecular and cellular biology.

[20]  S. Sehgal,et al.  Rapamycin (AY-22,989), a new antifungal antibiotic. III. In vitro and in vivo evaluation. , 1978, The Journal of antibiotics.

[21]  Jason C. Young,et al.  Specific Binding of Tetratricopeptide Repeat Proteins to the C-terminal 12-kDa Domain of hsp90* , 1998, The Journal of Biological Chemistry.

[22]  J. Macdonald,et al.  Chicken FK506-binding protein, FKBP65, a member of the FKBP family of peptidylprolyl cis-trans isomerases, is only partially inhibited by FK506. , 1998, The Biochemical journal.

[23]  T. Kiefhaber,et al.  Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins , 1989, Nature.

[24]  R. Stein,et al.  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. , 1990, Biochemistry.

[25]  T. Muramatsu,et al.  Reticulocalbin, a novel endoplasmic reticulum resident Ca(2+)-binding protein with multiple EF-hand motifs and a carboxyl-terminal HDEL sequence. , 1993, The Journal of biological chemistry.

[26]  J. Kay.  Structure-function relationships in the FK506-binding protein (FKBP) family of peptidylprolyl cis-trans isomerases. , 1996, The Biochemical journal.

[27]  R. Kretsinger,et al.  Structure and evolution of calcium-modulated proteins. , 1980, CRC critical reviews in biochemistry.

[28]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[29]  A. Galat,et al.  Peptidylproline cis-trans-isomerases: immunophilins. , 1993, European journal of biochemistry.

[30]  D. V. van Thiel,et al.  Liver transplantation (2). , 1989, The New England journal of medicine.

[31]  M. Kozak.  Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes , 1986, Cell.

[32]  D. Fruman,et al.  Immunophilins in protein folding and immunosuppression 1 , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[33]  P. Katz,et al.  The effect of cyclosporine on the use of hospital resources for kidney transplantation. , 1989, The New England journal of medicine.

[34]  C. Morris,et al.  A novel human gene FKBP6 is deleted in Williams syndrome. , 1998, Genomics.

[35]  J. Hacker,et al.  Immunophilins: structure—function relationship and possible role in microbial pathogenicity , 1993, Molecular microbiology.

[36]  H. Erdjument-Bromage,et al.  FK506 binding protein associated with the calcium release channel (ryanodine receptor). , 1992, The Journal of biological chemistry.

[37]  D. Macer,et al.  Identification of a set of calcium-binding proteins in reticuloplasm, the luminal content of the endoplasmic reticulum. , 1988, Journal of cell science.

[38]  S. Snyder,et al.  Immunophilins and nervous system , 1995, Nature Medicine.

[39]  C. Morris,et al.  A novel human gene, WSTF, is deleted in Williams syndrome. , 1998, Genomics.

[40]  P. Donahoe,et al.  Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12. , 1994, Science.

[41]  S. Schreiber.  Immunophilin-sensitive protein phosphatase action in cell signaling pathways , 1992, Cell.

[42]  S. Snyder,et al.  The 13-kD FK506 Binding Protein, FKBP13, Interacts with a Novel Homologue of the Erythrocyte Membrane Cytoskeletal Protein 4.1 , 1998, The Journal of cell biology.

[43]  Nolan H. Sigal,et al.  A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin , 1989, Nature.

[44]  C. S. Raymond,et al.  Molecular Cloning, DNA Sequence Analysis, and Biochemical Characterization of a Novel 65-kDa FK506-binding Protein (FKBP65) * , 1995, The Journal of Biological Chemistry.

[45]  R. Mecham,et al.  Identification of Tropoelastin as a Ligand for the 65-kD FK506-binding Protein, FKBP65, in the Secretory Pathway , 1998, The Journal of cell biology.

[46]  S. Snyder,et al.  Neural actions of immunophilin ligands. , 1998, Trends in pharmacological sciences.

[47]  C A Morris,et al.  Natural history of Williams syndrome: physical characteristics. , 1988, The Journal of pediatrics.

[48]  S. Munro,et al.  A C-terminal signal prevents secretion of luminal ER proteins , 1987, Cell.

[49]  Paul Tempst,et al.  RAFT1: A mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs , 1994, Cell.

[50]  T. Honjo,et al.  Molecular cloning, characterization, and chromosomal localization of FKBP23, a novel FK506-binding protein with Ca2+-binding ability. , 1998, Genomics.

[51]  H. Pelham,et al.  Sorting of soluble ER proteins in yeast. , 1988, The EMBO journal.

[52]  Gunnar von Heijne,et al.  Patterns of Amino Acids near Signal‐Sequence Cleavage Sites , 1983 .

[53]  J. H. Li,et al.  Neurotrophic immunophilin ligands stimulate structural and functional recovery in neurodegenerative animal models. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[54]  B. Bierer,et al.  Localization of the FK506-binding protein, FKBP 13, to the lumen of the endoplasmic reticulum. , 1993, The Biochemical journal.

[55]  Paul Horton,et al.  Better Prediction of Protein Cellular Localization Sites with the it k Nearest Neighbors Classifier , 1997, ISMB.

[56]  J. Massagué,et al.  Mechanism of TGFβ receptor inhibition by FKBP12 , 1997, The EMBO journal.

[57]  R F Standaert,et al.  Atomic structure of FKBP-FK506, an immunophilin-immunosuppressant complex , 1991, Science.

[58]  A. Lamond,et al.  The endoplasmic reticulum calcium-binding protein of 55 kDa is a novel EF-hand protein retained in the endoplasmic reticulum by a carboxyl-terminal His-Asp-Glu-Leu motif. , 1994, The Journal of biological chemistry.