Logo image
Back
FKBP46, a novel Sf9 insect cell nuclear immunophilin that forms a protein-kinase complex
Journal article   Open access   Peer reviewed

FKBP46, a novel Sf9 insect cell nuclear immunophilin that forms a protein-kinase complex

E S Alnemri, T Fernandes-Alnemri, K Pomerenke, N M Robertson, K Dudley, G C DuBois and G Litwack
The Journal of biological chemistry, v 269(49), pp 30828-30834
09 Dec 1994
DOI: https://doi.org/10.1016/S0021-9258(18)47356-5
PMID: 7527037
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1016/S0021-9258(18)47356-5View
Published, Version of Record (VoR) Open

Abstract

Amino Acid Isomerases - metabolism Amino Acid Sequence Animals Baculoviridae - genetics Base Sequence Carrier Proteins - genetics Carrier Proteins - metabolism Cell Nucleus - metabolism DNA, Complementary DNA-Binding Proteins - genetics Heat-Shock Proteins - genetics Mice Molecular Sequence Data Peptidylprolyl Isomerase Protein Kinases - metabolism Recombinant Fusion Proteins - genetics Sequence Homology, Amino Acid Spodoptera Tacrolimus - metabolism Tacrolimus Binding Proteins
Recently, we identified a 59-kDa nuclear phosphoprotein that is associated with a recombinant mouse FKBP-52 (Alnemri, E. S., Fernandes-Alnemri, T., Nelki, D. S., Dudley, K., DuBois, G. C., and Litwack, G. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 6839-6843). Here we describe the cloning, overexpression, and characterization of this protein from Spodoptera frugiperda insect cells (Sf9 cells). The cloned cDNA codes for an acidic protein of 412 amino acids with distinct structural domains. Starting with the N terminus, the first 218 amino acids contain two highly acidic domains separated by a short basic domain. Following the second large acidic domain is another basic domain of 87 amino acids with significant sequence and structural homology to HMG1 and HMG2 DNA binding proteins. The two basic domains contain several nuclear targeting signals. The last 108 C-terminal amino acids contain a binding domain for immunosuppressive drugs FK506 and rapamycin, which makes this protein a new member of the immunophilin family. We provide evidence that the new immunophilin (FKBP46) is a DNA binding protein that can bind immunosuppressive drug FK506 and possesses peptidylprolyl isomerase activity. FKBP46 is localized in the nucleus and is associated with a nuclear kinase that specifically phosphorylates it in the presence of Mg2+ and ATP. Upon subsequent sequence analysis of the mouse FKBP52 cDNA used in our previous study, it was observed that a spermatid nuclear transition protein 2 (TP2) sequence is fused in frame with the C terminus of the recombinant FKBP52 probably as a result of a cloning artifact. We demonstrate that the FKBP46 does not form a complex with the FKBP52 but rather with the highly basic nuclear protein TP2. Our data suggest that interaction of FKBP46 with TP2 is mediated by the N-terminal acidic domains of FKBP46. This implies that the acidic domains of FKBP46 are involved in protein-protein interaction between nuclear FKBP46 and other basic chromatin proteins.

Metrics

10 Record Views
41 citations in Web of Science

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Logo image