Parvulins

Parvulins are a family of peptidyl-prolyl cis-trans isomerases (PPIases) that belong to the parvulin subfamily. They catalyze the cis-trans isomerization of peptide bonds preceding proline residues, a reaction that can influence protein folding, conformational switching, and signaling. By altering the shape of substrate proteins, parvulins can regulate activity, stability, interactions, and subcellular localization.

In humans, the best-characterized member is Pin1, a multifunctional protein with an N-terminal domain that recognizes phosphorylated Ser/Thr-Pro motifs and a C-terminal parvulin-type PPIase domain. This arrangement allows Pin1 to bind phosphoproteins and accelerate prolyl isomerization, thereby modulating the function of substrates such as cyclin D1, p53, and other signaling and cell-cycle regulators. Other vertebrate parvulins include smaller proteins such as Par14 and Par17, which share a parvulin PPIase domain but differ in localization and regulatory interactions.

Parvulins are broadly distributed across life, occurring in bacteria, archaea, and eukaryotes. Bacterial parvulin homologs function as PPIases and contribute to protein folding and stress responses, with roles that vary between species. The structure of parvulins typically centers on a conserved catalytic core of the parvulin PPIase domain; in some proteins, this domain is part of a larger, modular architecture that provides substrate targeting or regulatory control.

Clinical and research relevance: due to their involvement in cell cycle control and signaling, parvulins—especially Pin1—are studied as potential targets for cancer and neurodegenerative disease therapies. Inhibiting parvulin activity can influence the fate of multiple signaling proteins and pathways.