FK506-binding protein gene

Details FK506-binding protein gene FK506-binding protein gene

1998-07-15

2000-10-24

Wax, Robert A.

Chemistry: molecular biology and microbiology

Enzyme , proenzyme; compositions thereof; process for...

Isomerase

C12N 990

Patent

active

06136584&

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to an FK506 binding protein gene.


BACKGROUND ART

FK506 is a potent immunosuppressant and, like cyclosporin A [Borel, J. G. et al., Agents and Actions, 6, 468-471 (1976)], it is often used for preventing allograft rejection [Thomson, A. W., Immunol. Today, 10, 6-9 (1989)]. It is considered that the mechanism of its immunosuppresant action is in focus on the suppression of translation, during T cell activation [Tocci, M. et al., J. Immunol., 143, 718-726 (1989)], of a series of lymphokine genes which is critical to early immune responses. However, the precise mechanism remains unclear.
Recently, an AF506 binding protein was found in human T cells. It was identified as the 12 kDa cytosolic receptor of FK506 and shown to have peptidylprolyl cistrans isomerase activity (PPIase activity) [Siekier, J. et al., J. Immunol., 143, 1580-1583 (1989)].
Subsequently, on the basis of its amino acid sequence, a number of FK506 binding proteins (FKBPs) and corresponding cDNA clones have been isolated and the nucleotide sequences of said clones have been determined [for example, human FKBPs such as FKBP-12 (Standaert, R. F. et al., Nature, 346, 671-674 (1990); Maki, N, et al., Proc. Natl. Acad. Sci. USA, 87, 5440-5443 (1990)), FKBP-13 (Jin, Y. et al., Proc. Natl. Acad. Sci. USA, 88, 6677-6681 (1991)), FKBP-25 (Wiederrecht, G. et al., Biochem. Biophys. Res. Comm., 185, 298-303 (1992)) and FKBP-52 (Peattie, D. A. et al., Proc. Natl. Acad. Sci. USA, 89, 10974-10978 (1992)) as well as murine FKBP (Nelson, P. A. et al., Gene, 109, 255-258 (1991)), bovine FKBP (Mozier, N. M. et al., Eur. J. Biochem., 194, 19-23 (1990)), yeast FKBP (Heitman, J. et al., Proc. Natl. Acad. Sci. USA, 88, 1948-1952 (1991)), Neurospora crassa FKBP (Tropschug, M. et al., Nature, 346, 674-677 (1990)), Neisseria meningitis FKBP (Sampson, B. A. et al., Proc. Natl. Acad. Sci. USA, 89, 1164-1168 (1992)), etc]
The above-mentioned FKBPs all have PPIase activity, which is presumably essential for protein folding during protein synthesis in cells [Ficher, G. et al., Biomed. Biochim. Acta, 43, 1101-1111 (1984)]. Although no clear evidence is available to prove that said PPIase activity is necessary for T cell activation, binding of FK506 to FKBPs is believed to bring about inhibition of PPIase activity and thereby inactivate T cells [Tropschug, M. et al., Nature, 346, 674-677 (1990)].


DISCLOSURE OF THE INVENTION

Accordingly, it is an object of the present invention to provide a novel FK506 binding protein (FKBP) gene, more particularly a novel FKBP gene which is highly homologous to the above-mentioned human FKBP-12 and whose expression product protein has high PPIase activity.
As a result of their intensive investigations, the present inventors succeeded in isolating, from a human fetal brain cDNA library, a novel gene coding for a protein highly homologous to the human FK506 binding protein 12 kD (FKBP-12) and in determining its full-length cDNA sequence. Based on these results, they have now attained the present invention.
Thus, the present invention is directed to an FK506 binding protein gene coding for an amino acid sequence defined by the sequence shown under SEQ ID NO:1 or SEQ ID NO:2 in the sequence listing.
The abbreviations for amino acids, peptides, base sequences, nucleic acids and so forth as used herein in the present specification are those recommended by the International Union of Pure and Applied Chemistry (IUPAC) and the International Union of Biochemistry (IUB) and in the "Guidelines for drafting patent specifications relative to base sequences and/or amino acid sequences" edited by the Japanese Patent Office or those commonly used in the relevant field of art.
The gene of the present invention includes genes characterized in that they comprise an open reading frame consisting of a 324 nucleic acid sequence coding for the 108 amino acid residues as shown under the above-mentioned SEQ ID NO:1.
The gene of the present invention also includes genes characterized in that they comprise an open read

REFERENCES:
patent: 5457182 (1995-10-01), Wiederrecht et al.
Rosborough, S.L., et al., "Identification of FKBP-Related Proteins with Antibodies of Predetermined Specificity and Isolation by FK 506 Affinity Chromatography", Transplantation Proceedings, vol. 23, No. 6, pp. 2890-2893, (Dec. 1991).
Sewell, Tonya J. et al., "Inhibition of Calcineurin by a Novel FK-506-binding Protein", Journal of Biological Chemistry, vol. 269, No. 33, pp. 21094-21102, (Aug. 19, 1994).

Affiliated with

Also associated with

Rating

FK506-binding protein gene does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with FK506-binding protein gene, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and FK506-binding protein gene will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1962404