Immunophilin protein with PPIase and co-chaperone activities (By similarity). Component of unligated steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90) (By similarity). Plays a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments. May have a protective role against oxidative stress in mitochondria (By similarity). Acts also as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. The PPIase activity controls neuronal growth cones via regulation of TRPC1 channel opening. [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0) Inhibited by FK506. Homodimer (By similarity). Interacts with GLMN. Associates with HSP90AA1 and HSP70 in steroid hormone receptor complexes. Also interacts with peroxisomal phytanoyl-CoA alpha-hydroxylase (PHYH). Interacts with NR3C1 and dynein. Interacts with HSF1 in the HSP90 complex (By similarity). Associates with tubulin (PubMed:17435176). Interacts with MAPT/TAU (PubMed:20133804). Interacts (via TPR domain) with S100A1, S100A2 and S100A6; the interaction is Ca(2+) dependent. Interaction with S100A1 and S100A2 (but not with S100A6) leads to inhibition of FKBP4-HSP90 interaction. Interacts with dynein; causes partially NR3C1 transport to the nucleus (By similarity). Shuttles from mitochondria to nucleus; co-localizes in mitochondria with the glucocorticoid receptor (By similarity). Colocalized with MAPT/TAU in the distal part of the primary cortical neurons (PubMed:20133804). Widely detected in the brain (at protein level). The PPIase activity is mainly due to the first PPIase FKBP-type domain (1-138 AA). The C-terminal region (AA 375-458) is required to prevent tubulin polymerization. The chaperone activity resides in the C-terminal region, mainly between amino acids 264 and 400. The TPR repeats mediate mitochondrial localization. Phosphorylation by CK2 results in loss of HSP90 binding activity. A mind astray - Issue 118 of June 2010