Prolyl endopeptidase (EC 3.4.21.26 ) is a large cytosolic enzyme that belongs to a distinct class of serine peptidases. The
enzyme is involved in the maturation and degradation of peptide hormones and neuropeptides. PREP cleaves peptide bonds
at the C-terminal side of proline residues. Its activity is confined to action on oligopeptides of less than 10 kD and it has an
absolute requirement for the trans-configuration of the peptide bond preceding proline.Also known as prolyl oligopeptidase, this enzyme shows sequence similarity with dipeptidyl peptidase IV.
NCBI Summary:
Prolyl endopeptidase; hydrolyses peptide bonds on the C-terminal side of proline residues
General function
Enzyme, Hydrolase, Peptidase/Protease
Comment
Epigenetic patterns at the mouse prolyl oligopeptidase gene locus suggest the CpG island in the gene body to be a novel regulator for gene expression. Matsubara S et al. Prolyl oligopeptidase (POP) is a widely distributed serine peptidase which hydrolyzes small peptides on the carboxyl side of an internal proline residue. While its physiological role has been intensely studied, the regulatory mechanism of the gene expression is poorly understood. This time we assessed the POP mRNA expression in mouse embryos and tissues related to reproduction and development and found that POP mRNA was highly expressed in the ovarian granulosa cell, placental spongiotrophoblast, and blastocyst embryo. To elucidate the mechanism by which POP expression is regulated, we investigated DNA methylation and histone modification patterns of the two CpG islands (CGIs) found at the mouse POP locus. Whereas the CGI including the POP promoter (CGI-1) was completely hypomethylated in all the tissues examined, DNA methylation level of the CGI in the gene body (CGI-2) was lower in the granulosa cell, placenta, and blastocyst than in the liver. Some specific CpGs in CGI-2 were significantly demethylated in the three tissues. An in vitro reporter analysis indicated that CGI-2 enhanced POP promoter activity and its effect was significantly reduced by DNA methylation. Moreover, histone H3 acetylation and H3K4 methylation levels of CGI-2 were higher in the granulosa cell than liver. The results suggest that the CGI-2 region is a cis-element for the POP gene expression.
Cellular localization
Cytoplasmic
Comment
Ovarian function
Luteinization, Luteolysis
Comment
Kimura A et al 2000 reported cDNA cloning of rat prolyl oligopeptidase and its expression in the ovary during
the estrous cycle. Northern blot analysis showed wide expression of the
prolyl oligopeptidase gene. Using ovaries from hormone-treated rats, it was found that both the mRNA
expression and enzyme activity increased in the luteal phase. These findings suggest the involvement
of prolyl oligopeptidase in events associated with corpus luteum formation and/or luteal regression.
Expression regulated by
LH
Comment
Ovarian localization
Granulosa, Luteal cells
Comment
Kimura et al 1978 reported localization of prolyl endopeptidase mRNA in small growing follicles of porcine
ovary. Both follicular fluid and
granulosa cell fractions from small follicles showed higher activity than those from large follicles.
Molecular cloning and Northern blot analysis suggested that only one species of prolyl endopeptidase
gene was expressed in the ovary. In addition, in situ hybridization study revealed that the prolyl
endopeptidase mRNA expression was more noticeable in the granulosa cell layers of small ovarian
follicles than in those of large follicles, suggesting its importance in the early stage of follicular
development. Localization of prolyl endopeptidase mRNA in small growing follicles of porcine ovary.