FK506 Binding Protein 14 Human Recombinant
FK506 Binding Protein 1A Human Recombinant
FK506 Binding Protein 1A Mouse Recombinant
FK506 Binding Protein 1B Human Recombinant
FK506 Binding Protein 2 Human Recombinant
FK506 Binding Protein 3 Human Recombinant
FK506 Binding Protein 4 Human Recombinant
FK506 Binding Protein 5 Human Recombinant
FK506 Binding Protein 6 Human Recombinant
FK506 Binding Protein Like Human Recombinant
FKBPL Recombinant Human produced in E.Coli is a single, non-glycosylated polypeptide chain containing 357 amino acids (1-349 a.a.) and having a molecular mass of 39.2 kDa. The FKBPL is fused to an 8 amino acid His-Tag at C-terminus and purified by proprietary chromatographic techniques.
FK506 Binding Proteins (FKBPs) are a family of proteins that possess peptidyl-prolyl cis-trans isomerase activity, facilitating the folding of proteins containing proline residues . They are classified as immunophilins due to their ability to bind immunosuppressive drugs such as FK506 (tacrolimus) and rapamycin . FKBPs are found in a wide range of organisms, from yeast to humans .
Key Biological Properties: FKBPs exhibit peptidyl-prolyl isomerase activity, which is crucial for protein folding and function . They also play roles in various cellular processes, including signal transduction and protein trafficking .
Expression Patterns and Tissue Distribution: FKBPs are ubiquitously expressed in various tissues. For instance, FKBP12 is abundantly present in the cytoplasm and nucleus of cells . FKBP25, another member of the family, is primarily found in the nucleus and is involved in DNA repair .
Primary Biological Functions: FKBPs are involved in protein folding, cellular signaling, apoptosis, and transcription . They act as molecular switches by binding and altering the conformation of their target proteins .
Role in Immune Responses and Pathogen Recognition: FKBP12, in particular, binds to the immunosuppressant molecule tacrolimus, which inhibits the activity of calcineurin, a phosphatase involved in T-cell activation . This inhibition suppresses the immune response, making FKBP12 crucial in preventing organ rejection in transplant patients .
Mechanisms with Other Molecules and Cells: FK506 (tacrolimus) binds to FKBP12, forming a complex that inhibits calcineurin . This inhibition prevents the dephosphorylation and activation of nuclear factor of activated T-cells (NFAT), thereby suppressing the transcription of interleukin-2 (IL-2) and other cytokines .
Binding Partners and Downstream Signaling Cascades: The FKBP12-tacrolimus complex inhibits the calcineurin-dependent NFAT pathway and the calcineurin-independent activation pathway for JNK and p38 . This dual inhibition is critical for the immunosuppressive effects of tacrolimus .
Regulatory Mechanisms Controlling Expression and Activity: The expression of FKBP genes is regulated by various transcription factors and signaling pathways . For example, the fkbR and fkbN genes positively regulate FK506 biosynthesis in Streptomyces tsukubaensis .
Transcriptional Regulation and Post-Translational Modifications: FKBP expression is controlled at the transcriptional level by regulatory elements within their gene clusters . Post-translational modifications, such as phosphorylation, also play a role in modulating FKBP activity .
Biomedical Research: FKBPs are used as tools for chemically induced dimerization, which allows researchers to manipulate protein localization, signaling pathways, and protein activation .
Diagnostic Tools and Therapeutic Strategies: FKBP12 is targeted by immunosuppressive drugs like tacrolimus, which are used to prevent organ rejection in transplant patients and treat autoimmune disorders . Additionally, FKBP inhibitors are being explored for their potential in cancer therapy .
Role Throughout the Life Cycle: FKBPs are involved in various stages of development and aging. They participate in signal transduction, hormonal pathways, stress responses, and gene transcription . Mutations or dysregulation of FKBP genes can lead to developmental abnormalities and diseases .
From Development to Aging and Disease: FKBP12 regulates fundamental aspects of cell biology, including TGF-β receptor signaling, which is crucial for development and tissue homeostasis . Dysregulation of FKBP12 has been associated with diseases such as Alzheimer’s and cardiovascular diseases .