Dipeptidylpeptidase IV (DPP4; EC 3.4.14.5 ) is a serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides. DPP4 is identical to ADA complexing protein-2 and to the T-cell activation
antigen CD26. It is an intrinsic membrane glycoprotein anchored into the cell membrane by its N-terminal end. High levels of the enzyme are found in the brush-border membranes of the kidney proximal tubule and of the small intestine, but several other tissues also express the enzyme. From a colon cancer cell line, Darmoul et al. (1990) isolated a cDNA probe for intestinal dipeptidylpeptidase IV and, by Southern analysis of
somatic cell hybrids, assigned the gene to chromosome 2.
NCBI Summary:
The protein encoded by this gene is identical to adenosine deaminase complexing protein-2, and to the T-cell activation antigen CD26. It is an intrinsic membrane glycoprotein and a serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides. [provided by RefSeq, Jul 2008]
General function
Enzyme, Hydrolase, Peptidase/Protease
Comment
DPP IV is a membrane-bound peptidase and has its catalytic domain at extracellular sites.
Cellular localization
Plasma membrane
Comment
Dipeptidyl Peptidase 4 serum activity and concentration are increased in women with polycystic ovary syndrome. Blauschmidt S et al. (2017) Polycystic ovary syndrome (PCOS) is a complex disease, the etiology of which is not well understood. Alterations in potential candidate genes involved in the biosynthesis and metabolism of androgens, folliculogenesis, and insulin and glucose metabolism have been suggested as possible etiologies. Dipeptidyl peptidase-4 (DPP4) plays a key role in glucose homeostasis and, thus, in the regulation of insulin secretion. The aim of our study was to analyze the DPP4 activity and concentrations in the serum of PCOS and non-PCOS patients and, additionally, study the activation of the DPP4 promoter by androgens in vitro. Serum samples were obtained from 288 female patients treated at the Center for Reproductive Medicine and Andrology (154 non-PCOS and 134 PCOS patients). DPP4 activity was measured by the conversion of the DPP4 substrate Gly-Pro p-nitroanilide hydrochloride and DPP4 concentration with a commercial ELISA. Luciferase reporter assays, qPCR and Western Blot analyses were performed for the in vitro evaluation of the activation of the DPP4 promoter by androgens. DPP4 serum activity was increased in women with PCOS, regardless of which Rotterdam criteria led to the PCOS diagnosis. Furthermore, DPP4 serum levels were strongly correlated with the anti-Müllerian hormone (AMH) serum level. In vitro, the DPP4 promoter was stimulated by androgens in luciferase reporter assays, and DPP4 mRNA expression was increased in KGN granulosa carcinoma cells after androgen treatment. The results suggested that a deregulation of DPP4 serum levels could be an additional characteristic of the metabolic imbalances associated with PCOS. This article is protected by copyright. All rights reserved.//////////////////
Ovarian function
Comment
Expression regulated by
Growth Factors/ cytokines
Comment
Human granulosa cells obtained from patients who had undergone in vitro fertilization were cultured for 7 days in the absence (controls) or presence of hCG, tumor necrosis factor-alpha (TNF alpha), or interleukin 1-alpha (IL-1 alpha). Fujiwara et al. (1994) reported that flow cytometry showed that the percentage of cultured granulosa cells treated with TNF alpha and IL-1 alpha that was positive for DPPIV expression was significantly higher than that in controls, whereas hCG treatment produced no remarkable difference in DPPIV expression. The DPPIV activity of cells treated with TNF alpha and IL-1 alpha was also significantly higher than that of controls, whereas hCG treatment produced no significant difference from control values.
Ovarian localization
Granulosa, Theca, Luteal cells
Comment
Fujiwara et al. (1992) examined the expression of dipeptidyl peptidase IV (DPP IV) in human granulosa cells, thecal cells of growing, preovulatory, and atretic follicles, as well as corpora lutea. Indirect immunofluorescence staining of ovarian tissues with specific monoclonal antibodies revealed that DPP IV was present in large and small luteal cells in corpora lutea. DPP IV peptidase activity was also detected histochemically in corpora lutea. In growing, preovulatory, and atretic follicles, there was weak immunoreactivity and DPP IV peptidase activity on luteinized theca interna cells, but not on granulosa cells.
Follicle stages
Antral, Preovulatory, Corpus luteum
Comment
Fujiwara et al. (1993) raised a monoclonal antibody (OG-1) specifically reactive to human ovarian granulosa cells.
Indirect immunofluorescence staining of freshly isolated granulosa cells from preovulatory follicles showed the OG-1 antigen on the cell surface of granulosa cells. The antigen was purified from granulosa cells by immunoaffinity chromatography.