FKBP3, also known as FKBP25, contains the N-terminal basic tilted helix bundle (BTHB) domain and the C-terminal PPIase domain. It is a nuclear prolyl isomerase that interacts directlywith nucleic acids []. It interacts with the histone deacetylases HDAC1 and HDAC2 as well as with their transcriptional regulator Yin Yang 1 (YY1) []. It is also a microtubule-associated protein that shuttles between nucleus and cytoplasm and stabilizes the microtubule network by direct binding of the C-terminal PPIase domain []. It plays a role in the proliferation of non-small cell type lung cancer cells (NSCLC) by modulating Sp1/HDAC2/p27 [].
This domain is found on the N-terminal region of peptidyl-prolyl cis-trans isomerase FKBP3 and in the core region of E3 ubiquitin ligase HectD1. It adopts a compact 5-helix bundle, hence termed BTHB (Basic Tilted Helix Bundle) domain. In FKBP3, it has been suggested to have a role in regulating the association state of nucleosomes by interacting with nucleolin. Moreover, this basic domain in FKBP35 forms alternative complexes with other chromatin-related proteins, such as the HDAC1, HDAC2, and the transcriptional regulator YY1, the DNA binding activity of which is enhanced on binding FKBP3. Structural analysis of this fold suggests that the DNA binding properties of FKBP3 and HectD1 are presented by the conserved basic region [].
