UniProt functional annotation for Q02790

UniProt code: Q02790.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
 
Function: Immunophilin protein with PPIase and co-chaperone activities. Component of steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments. The isomerase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Acts also as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. May have a protective role against oxidative stress in mitochondria. {ECO:0000269|PubMed:1279700, ECO:0000269|PubMed:1376003, ECO:0000269|PubMed:19945390, ECO:0000269|PubMed:21730050, ECO:0000269|PubMed:2378870}.
 
Catalytic activity: Peptidylproline (omega=180) = peptidylproline (omega=0).
Enzyme regulation: Inhibited by FK506. {ECO:0000269|PubMed:1279700}.
Subunit: Homodimer (By similarity). 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. Associates with tubulin. Interacts with MAPT/TAU. 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. {ECO:0000250, ECO:0000269|PubMed:11583998, ECO:0000269|PubMed:1376003, ECO:0000269|PubMed:1383226, ECO:0000269|PubMed:15159550, ECO:0000269|PubMed:19945390, ECO:0000269|PubMed:20188096, ECO:0000269|PubMed:21730050, ECO:0000269|PubMed:2378870}.
Subcellular location: Cytoplasm, cytosol {ECO:0000250}. Mitochondrion. Nucleus. Cytoplasm, cytoskeleton {ECO:0000250}. Note=Shuttles from mitochondria to nucleus; co-localizes in mitochondria with the glucocorticoid receptor.
Tissue specificity: Widely expressed. {ECO:0000269|PubMed:1279700}.
Domain: The PPIase activity is mainly due to the fisrt PPIase FKBP-type domain (1-138 AA). {ECO:0000250}.
Domain: The C-terminal region (AA 375-458) is required to prevent tubulin polymerization. {ECO:0000250}.
Domain: The chaperone activity resides in the C-terminal region, mainly between amino acids 264 and 400. {ECO:0000250}.
Domain: The TPR repeats mediate mitochondrial localization.
Ptm: Phosphorylation by CK2 results in loss of HSP90 binding activity. {ECO:0000250}.
Similarity: Contains 2 PPIase FKBP-type domains. {ECO:0000255|PROSITE-ProRule:PRU00277}.
Similarity: Contains 3 TPR repeats. {ECO:0000255|PROSITE- ProRule:PRU00339}.

Annotations taken from UniProtKB at the EBI.