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Gene Review

PGPEP1  -  pyroglutamyl-peptidase I

Homo sapiens

Synonyms: 5-oxoprolyl-peptidase, PAP-I, PGP, PGP-I, PGPI, ...
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Disease relevance of PGPEP1

  • In parallel, three proteasome proteolytic activities (CTL, chymotrypsin-like; TL, trypsin-like; PGP, peptidyl-glutamyl-peptidase) significantly increased in gastric cancer patients with respect to controls [1].
  • Soluble and particulate pyroglutamyl peptidase I activities, aminopeptidase A activity, and soluble aminopeptidase B activity do not vary in renal cancer [2].
  • Investigations on enzymatic properties showed that the Pcp over-expressed in E. coli disclosed properties similar to those found for the enzyme extracted from S. pyogenes or for some other Pcps studied previously [3].
  • Technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI) and thallium-201 imaging was performed in a patient with metastatic renal cell carcinoma (RCC), which is a well-known tumour type demonstrating P1-glycoprotein (PGP) overexpression [4].
  • CONCLUSIONS: PGP 9.5-immunoreactivity is prenatally distributed in the Wolffian duct and its derivations; postnatally, it is restricted to a few cells derived from the initial and terminal segment of the Wolffian duct, and to neuroendocrine cells in prostate cancer specimens [5].

High impact information on PGPEP1


Chemical compound and disease context of PGPEP1


Biological context of PGPEP1

  • As an impaired enzyme function caused by genetic alterations might increase the amount of immunogenic gluten peptides, we conducted a comprehensive functional genomics analysis of PGPEP1, including DNA sequencing, genetic association testing, and quantifying RNA expression [11].
  • We describe the cloning and sequencing of the human (AJ278828) and mouse (AJ278829) forms of pyroglutamyl-peptidase I. The deduced amino acid sequences each consist of 209 residues and show approximately 30% identity with bacterial forms of the enzyme [12].
  • Wash-out kinetics of 99mTc-MIBI and the scintigraphic determination of PGP expression [13].
  • Pyrrolidone carboxyl peptidase (EC (Pcp), an enzyme which selectively removes pyrrolidone carboxylic acid (PCA) from some PCA-peptides and -proteins, was demonstrated in bacteria and in plant, animal and human tissues [3].
  • To study the possible involvement of TRH neurons in learning and memory processes, gene expression of TRH, its receptors, and pyroglutamyl peptidase (PPII), were measured in limbic regions of water-maze trained rats [14].

Anatomical context of PGPEP1

  • Pyroglutamyl peptidase I and prolyl endopeptidase in human semen: increased activity in necrozoospermia [15].
  • In the ejaculatory ducts, the PGP 9.5-immunoreactive cells were free of immunoreactivity for semenogelin, the major secretory product of the ejaculatory-vesicular-ampullary complex, and they also lacked chromogranin A-immunoreactivity [5].
  • Moreover, fluoxetine (10 micro M) induces approximately 30% inhibition of PGP activity in Caco-2 cells [16].
  • Nerve fibers were revealed using immunoperoxidase staining with panaxonal antibody PGP 9 [17].
  • Numerous weakly-to-strongly PGP 9.5-immunoreactive cells were found both in the epidermis and in the dermis [18].

Associations of PGPEP1 with chemical compounds

  • Cellular efflux of auxin catalyzed by the Arabidopsis MDR/PGP transporter AtPGP1 [7].
  • Proteins with N-terminal pyroglutamic acid were enzymatically deblocked by in situ pyroglutamyl peptidase digestion, and N-acetylated proteins were also enzymatically deblocked with acylamino acid-releasing enzyme (AARE) after on-membrane digestion with trypsin to generate the N-terminal peptide fragment [19].
  • In contrast, PGP ATPase activity was increased by PKC alpha as well as by verapamil, but only PKC-stimulated activity in the presence of verapamil was inhibited by Ro 31-8220 [9].
  • We have developed two new prodrugs, 4-[N,N-bis(2-chloroethyl)amino]-phenoxycarbonyl-L- glutamic acid (PGP) and (S)-2-[N-[4-[N,N-bis(2-chloroethyl)amino]- phenoxycarbonyl]amino]-4-(5-tetrazoyl)butyric acid (PTP), which are cleaved by the bacterial enzyme CPG2 to release the 4-[N,N-bis(2-chloroethyl)amino] phenol drug [20].
  • As compared to controls, an increased number of PGP-, SP- and CGRP-immunoreactive nerves were demonstrated in the mucosa in 9/10 OSA patients and 4/11 snorers, in addition to varicose nerve endings in the papillae and epithelium [21].

Physical interactions of PGPEP1


Other interactions of PGPEP1


Analytical, diagnostic and therapeutic context of PGPEP1


  1. Increased muscle proteasome activity correlates with disease severity in gastric cancer patients. Bossola, M., Muscaritoli, M., Costelli, P., Grieco, G., Bonelli, G., Pacelli, F., Rossi Fanelli, F., Doglietto, G.B., Baccino, F.M. Ann. Surg. (2003) [Pubmed]
  2. Altered levels of acid, basic, and neutral peptidase activity and expression in human clear cell renal cell carcinoma. Varona, A., Blanco, L., López, J.I., Gil, J., Agirregoitia, E., Irazusta, J., Larrinaga, G. Am. J. Physiol. Renal Physiol. (2007) [Pubmed]
  3. One step purification and characterization of the pyrrolidone carboxyl peptidase of Streptococcus pyogenes over-expressed in Escherichia coli. Awadé, A., Gonzalès, T., Cleuziat, P., Robert-Baudouy, J. FEBS Lett. (1992) [Pubmed]
  4. 99mTc-MIBI scintigraphy in metastatic renal cell carcinoma: clinical validation of the relationship between 99mTc-MIBI uptake and P-glycoprotein expression in tumour tissue. Derebek, E., Kirkali, Z., Dogan, A.S., Degirmenci, B., Yilmaz, M., Igci, E., Yorukoglu, K., Kovanlikaya, I., Durak, H. European journal of nuclear medicine. (1996) [Pubmed]
  5. Localization of protein gene product 9.5 immunoreactivity in derivatives of the human Wolffian duct and in prostate cancer. Aumüller, G., Renneberg, H., Leonhardt, M., Lilja, H., Abrahamsson, P.A. Prostate (1999) [Pubmed]
  6. Autonomic denervation in jejunal mucosa of homosexual men infected with HIV. Batman, P.A., Miller, A.R., Sedgwick, P.M., Griffin, G.E. AIDS (1991) [Pubmed]
  7. Cellular efflux of auxin catalyzed by the Arabidopsis MDR/PGP transporter AtPGP1. Geisler, M., Blakeslee, J.J., Bouchard, R., Lee, O.R., Vincenzetti, V., Bandyopadhyay, A., Titapiwatanakun, B., Peer, W.A., Bailly, A., Richards, E.L., Ejendal, K.F., Smith, A.P., Baroux, C., Grossniklaus, U., Müller, A., Hrycyna, C.A., Dudler, R., Murphy, A.S., Martinoia, E. Plant J. (2005) [Pubmed]
  8. Tannic acid synergizes the cytotoxicity of chemotherapeutic drugs in human cholangiocarcinoma by modulating drug efflux pathways. Naus, P.J., Henson, R., Bleeker, G., Wehbe, H., Meng, F., Patel, T. J. Hepatol. (2007) [Pubmed]
  9. Modulation of P-glycoprotein by protein kinase C alpha in a baculovirus expression system. Ahmad, S., Safa, A.R., Glazer, R.I. Biochemistry (1994) [Pubmed]
  10. Benarthin: a new inhibitor of pyroglutamyl peptidase. III. Synthesis and structure-activity relationships. Hatsu, M., Tuda, M., Muraoka, Y., Aoyagi, T., Takeuchi, T. J. Antibiot. (1992) [Pubmed]
  11. Genetic and functional analysis of pyroglutamyl-peptidase I in coeliac disease. Monsuur, A.J., Stepniak, D., Diosdado, B., Wapenaar, M.C., Mearin, M.L., Koning, F., Wijmenga, C. European journal of gastroenterology & hepatology. (2006) [Pubmed]
  12. Pyroglutamyl-peptidase I: cloning, sequencing, and characterisation of the recombinant human enzyme. Dando, P.M., Fortunato, M., Strand, G.B., Smith, T.S., Barrett, A.J. Protein Expr. Purif. (2003) [Pubmed]
  13. Wash-out kinetics of 99mTc-MIBI and the scintigraphic determination of PGP expression. Derebek, E., Değirmenci, B., Durak, H. European journal of nuclear medicine. (1997) [Pubmed]
  14. The expression of TRH, its receptors and degrading enzyme is differentially modulated in the rat limbic system during training in the Morris water maze. Aguilar-Valles, A., Sánchez, E., de Gortari, P., García-Vazquez, A.I., Ramírez-Amaya, V., Bermúdez-Rattoni, F., Joseph-Bravo, P. Neurochem. Int. (2007) [Pubmed]
  15. Pyroglutamyl peptidase I and prolyl endopeptidase in human semen: increased activity in necrozoospermia. Valdivia, A., Irazusta, J., Fernández, D., Múgica, J., Ochoa, C., Casis, L. Regul. Pept. (2004) [Pubmed]
  16. Antidepressant fluoxetine enhances glucocorticoid receptor function in vitro by modulating membrane steroid transporters. Pariante, C.M., Kim, R.B., Makoff, A., Kerwin, R.W. Br. J. Pharmacol. (2003) [Pubmed]
  17. A quantitative method for the assessment of intraepidermal nerve fibers in small-fiber neuropathy. Koskinen, M., Hietaharju, A., Kyläniemi, M., Peltola, J., Rantala, I., Udd, B., Haapasalo, H. J. Neurol. (2005) [Pubmed]
  18. Protein gene product 9.5-immunoreactive nerve fibres and cells in human skin. Wang, L., Hilliges, M., Jernberg, T., Wiegleb-Edström, D., Johansson, O. Cell Tissue Res. (1990) [Pubmed]
  19. Microsequence analysis of the N-terminally blocked proteins immobilized on polyvinylidene difluoride membrane by western blotting. Hirano, H., Komatsu, S., Kajiwara, H., Takagi, Y., Tsunasawa, S. Electrophoresis (1993) [Pubmed]
  20. Anti-tumour effects of an antibody-carboxypeptidase G2 conjugate in combination with phenol mustard prodrugs. Blakey, D.C., Davies, D.H., Dowell, R.I., East, S.J., Burke, P.J., Sharma, S.K., Springer, C.J., Mauger, A.B., Melton, R.G. Br. J. Cancer (1995) [Pubmed]
  21. Abnormal afferent nerve endings in the soft palatal mucosa of sleep apnoics and habitual snorers. Friberg, D., Gazelius, B., Hökfelt, T., Nordlander, B. Regul. Pept. (1997) [Pubmed]
  22. Rapid inactivation and phosphorylation of pyroglutamyl peptidase II in Y-79 human retinoblastoma cells after exposure to phorbol ester. Suen, C.S., Wilk, S. Endocrinology (1990) [Pubmed]
  23. Activity of some proteolytic enzymes in normal and dystrophic human muscle. Kar, N.C., Pearson, C.M. Clin. Biochem. (1979) [Pubmed]
  24. Identification of a human CD4-CDR3-like surface involved in CD4+ T cell function. Friedman, T.M., Reddy, A.P., Wassell, R., Jameson, B.A., Korngold, R. J. Biol. Chem. (1996) [Pubmed]
  25. GAP-43 immunoreactivity of subepithelial and detrusor muscle nerve fibres in patients with refractory idiopathic detrusor overactivity. Schofield, E.C., Clausen, J.A., Burcher, E., Moore, K.H. Neurourology and urodynamics. (2005) [Pubmed]
  26. Nerve distribution in hemangiomas depends on the proliferative state of the microvasculature. Jang, Y.C., Isik, F.F., Gibran, N.S. J. Surg. Res. (2000) [Pubmed]
  27. Partial purification and some properties of pyroglutamyl peptidase from Enterococcus faecalis. Mineyama, R., Saito, K. Microbios (1998) [Pubmed]
  28. Impaired Tc-99m MIBI uptake in the thyroid and parathyroid glands during early phase imaging in hemodialysis patients. Kiratli, P.O., Ceylan, E., Naldöken, S., Beylergil, V. Revista española de medicina nuclear. (2004) [Pubmed]
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