Peptidyl-prolyl cis-trans isomerase (EC 5.2.1.8) (PPIase or rotamase) is an enzyme that accelerates protein folding by catalyzing the cis-trans isomerization of proline imidic peptide bonds in oligopeptides [1]. Most characterized PPiases belong to two families, the cyclophilin-type (see <PDOC00154>) and the the FKBP-type (see <PDOC00426>). Recently a third family has been discovered [2,3]. So far, the only biochemically characterized member of this family is the Escherichia coli protein parvulin (gene ppiC), a small (92 residues) cytoplasmic enzyme that prefers amino acid residues with hydrophobic side chains like leucine and phenylalanine in the P1 position of the peptides substrates. PpiC is evolutionary related to a number of proteins that are also probably PPiases:

• Escherichia coli and Haemophilus influenzae ppiD. PpiD is a PPIase which contains a periplasmic ppiC-like domain anchored to the inner membrane and which seems to be involved in the folding of outer membrane proteins.
• Escherichia coli surA. SurA is a periplasmic protein that contains two ppiC-like domains.
• Nitrogen-assimilating bacteria protein nifM which is involved in the activation and stabilization of the iron-component (nifH) of nitrogenase.
• Bacillus subtilis protein prsA, a membrane-bound lipoprotein involved in protein export.
• Lactococcus and lactobacillus protease maturation protein prtM, a membrane- bound lipoprotein involved in the maturation of a secreted serine proteinase.
• Yeast protein ESS1/PTF1 (processing/termination factor 1).
• Drosophila protein dodo (gene dod).
• Mammalian protein PIN1,
• Campylobacter jejuni cell binding factor 2 (CBF2), a secreted antigen.
• Bacillus subtilis hypothetical protein yacD.
• Helicobacter pylori hypothetical protein HP0175.
• A hypothetical slime mold protein.

As a signature pattern, we selected a conserved region that contains a serine which could play a role in the catalytic mechanism of these enzymes. We also developed a profile that spans the complete ppiC domain.