FKBP1A Human
Description
Product Specs
MAHHHHHHVMGVQVETISPGDGRTFPKRGQTCVV
HYTGMLEDGKKFDSSRDRNKPFKFMLGKQEVIRGW
EEGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPHAT
LVFDVELLKLE.
Product Science Overview
FK506 Binding Protein 1A (FKBP1A), also known as FKBP12, is a member of the FK506-binding protein family. These proteins are known for their role in immunosuppression and protein folding. FKBP1A is particularly notable for its ability to bind the immunosuppressant molecule tacrolimus (originally designated FK506), which is used in treating patients after organ transplant and those with autoimmune disorders .
FKBP1A is a peptidyl-prolyl cis-trans isomerase (PPIase), which means it catalyzes the isomerization of peptide bonds at proline residues in proteins. This activity is crucial for protein folding and function. The protein has a high affinity for FK506 and rapamycin, another immunosuppressant .
When FKBP1A binds to FK506, the complex inhibits the phosphatase activity of calcineurin. This inhibition blocks the signal transduction pathway in T-lymphocytes, preventing the activation of these immune cells and thereby exerting an immunosuppressive effect .
Beyond its role in immunosuppression, FKBP1A is involved in various cellular processes. It acts as a chaperone, assisting in the proper folding of proteins containing proline residues. FKBP1A also interacts with several other proteins and receptors, influencing pathways related to cell growth, differentiation, and apoptosis .
The ability of FKBP1A to bind FK506 and rapamycin has significant clinical implications. Tacrolimus is widely used to prevent organ rejection in transplant patients. It has been found to reduce episodes of organ rejection more effectively than ciclosporin, another immunosuppressant that binds to cyclophilin . Both the FKBP-tacrolimus complex and the cyclosporin-cyclophilin complex inhibit calcineurin, but tacrolimus has a higher potency.
FKBP1A is also a valuable tool in biological research. It does not normally form dimers but will dimerize in the presence of FK1012, a derivative of FK506. This property makes it useful for chemically induced dimerization applications, where it can be used to manipulate protein localization, signaling pathways, and protein activation .
FKBP1A shares homology with FKBP proteins found in other eukaryotes, ranging from yeast to humans. This evolutionary conservation suggests that FKBPs have fundamental roles in cellular physiology. Comparative studies have shown that FKBP proteins in mammals and Drosophila melanogaster (fruit flies) have similar functions, although there are differences in their mechanisms of action .
