Disease relevance of FPR2

• When expressed in and purified from Escherichia coli, both full-length Fpr3 and its isolated COOH-terminal domain exhibit readily detectable PPIase activity [1].

High impact information on FPR2

• In S. cerevisiae, the gene for a 112-residue cytosolic FKBP (FPR1) and the gene for a 135-residue ER-associated FKBP (FPR2) have been described before [1].
• The core region of VfFKBP15 is most similar to yeast and mammalian FKBP13 localized in the endoplasmic reticulum (ER) [2].
• As with KAR2, FKB2 mRNA levels are also elevated by heat shock [3].
• The similarities in the regulation of FKB2 and other ER chaperone genes suggest that FKBP-13 may play a role in protein trafficking in the ER [3].
• FKB2 mRNA levels are elevated in cells blocked in N-glycosylation--i.e., in wild-type cells treated with tunicamycin and in the sec53-6 mutant grown at the nonpermissive temperature [3].

Biological context of FPR2

• FKB2 is located on the right arm of chromosome IV and contains an open reading frame of 135 amino acids, of which the first 17 residues comprise a putative hydrophobic leader peptide [4].
• FKB2 encodes a homolog of human FKBP-13, a membrane-associated binding protein for the immunosuppressants FK506 and rapamycin [4].
• Recombinant Cyp40 produced in bacteria has a peptidyl-prolyl cis-trans isomerase activity with a catalytic efficiency (k[cat]/K[m]) of 0.5 x 10(6)M(-1)s(-1), which can be inhibited by cyclosporin A with an IC50 value of 60nM [5].

Anatomical context of FPR2

• The FKB2 gene of Saccharomyces cerevisiae, encoding the immunosuppressant-binding protein FKBP-13, is regulated in response to accumulation of unfolded proteins in the endoplasmic reticulum [3].

Associations of FPR2 with chemical compounds

• This protein, a peptidyl-prolyl cis-trans isomerase, is the yeast homologue of the protein that mediates the immunosuppressant effects of the drug cyclosporin A (CsA) [6].
• Furthermore, deletion of the entire PPIase domain did not significantly affect growth or Hsp90-mediated steroid receptor activity [7].
• The whole process of reactivation is catalysed by peptidyl prolyl cis-trans isomerase and thus suggests that one or more proline residues stereochemically control the rate limiting step of reactivation [8].

Other interactions of FPR2

• The reaction is not catalyzed by peptidyl-prolyl cis-trans isomerase of the cyclophilin type [9].

References