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Gene Review

QPCT  -  glutaminyl-peptide cyclotransferase

Homo sapiens

Synonyms: EC, GCT, Glutaminyl cyclase, Glutaminyl-peptide cyclotransferase, Glutaminyl-tRNA cyclotransferase, ...
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Disease relevance of QPCT

  • Three of the genes, QPCT, CYP1B1, and LXN, are densely methylated in >95% of uncultured melanoma tumor samples [1].
  • However, the results obtained for conversion of H-Gln-Gln-OH, H-Gln-NH2, and H-Gln-AMC were found to be contradictory to previous studies on human QC expressed intracellularly in E. coli [2].
  • CONCLUSIONS--The GCT repeat in myotonic dystrophy is highly mutable [3].
  • Triplet repeat polymorphism in the transmembrane region of the MICA gene: a strong association of six GCT repetitions with Behçet disease [4].
  • One, GCT, was isolated from a lung metastasis of a fibrous histiocytoma; the other, RC4, from a monocyte-enriched fraction of normal blood [5].

High impact information on QPCT

  • Prenatal measurement of the GCT triplet repeat has utility for families with myotonic dystrophy risk since mutant and normal repeats are distinguishable and the length of mutant repeat alleles is associated with clinical severity [3].
  • Crystal structures of human glutaminyl cyclase, an enzyme responsible for protein N-terminal pyroglutamate formation [6].
  • This N-terminal cyclization reaction, once thought to proceed spontaneously, is greatly facilitated by the enzyme glutaminyl cyclase (QC) [6].
  • To probe this important but poorly understood modification, we present here the structure of human QC in free form and bound to a substrate and three imidazole-derived inhibitors [6].
  • During nucleotide sequence analyses of the MICA genomic clone, we found a triplet repeat microsatellite polymorphism of (GCT/AGC)n in the transmembrane (TM) region of the MICA gene [4].

Chemical compound and disease context of QPCT


Biological context of QPCT


Anatomical context of QPCT

  • GCT, a human monocyte-like cell line, has been shown to release biochemically distinct colony-stimulating activities (CSAs) for mouse and human marrows [15].
  • Medium conditioned by well-developed MDLCCs (at day 21 to day 28 of cultivation) was added to bone marrow cultures containing GCT cell line-conditioned medium (GCT-CM) or other material as a source of granulocyte-macrophage colony-stimulating factors (GM-CSFs) [16].
  • CM depleted of acidic isoferritins or CM originally devoid of this activity (human GCT, 5637, Mo, lymphocytes: mouse L cells or pokeweed-mitogen-stimulated spleen cells) increased the sensitivity of the assay to detect acidic isoferritin inhibitory activity [17].
  • Some, such as GCT CM, stimulated both HL-60 cells and normal CFU-GM, whereas others, like HL-60 CM, stimulated only HL-60 growth [18].
  • Subcellular fractionation of GCT cells indicates that there are pools of preformed CSAs primarily associated with the cell cytosol that have similar apparent molecular weights to their secreted counterparts [15].

Associations of QPCT with chemical compounds

  • Here we report another example of genes: glutaminyl-peptide cyclotransferase gene (QPCT), an essential modifier of pituitary peptide hormones, including GnRH [12].
  • The effect of EDTA on QC catalysis was negligible [19].
  • The kinetically obtained pKa values of 6.94 +/- 0.02, 6.93 +/- 0.03, and 5.60 +/- 0.05 for imidazole, methylimidazole, and benzimidazole, respectively, match the values obtained by titrimetric pKa determination, indicating the requirement for an unprotonated nitrogen for binding to QC [19].
  • Human glutaminyl cyclase (QC) was identified as a metalloenzyme as suggested by the time-dependent inhibition by the heterocyclic chelators 1,10-phenanthroline and dipicolinic acid [19].
  • Comparisons of the protein sequences of QC from a variety of eukaryotic species show four completely conserved histidine residues [13].

Other interactions of QPCT

  • RESULTS: In each of the analyses a well defined melanoma component was identified that contained a gene coding for the enzyme, glutaminyl cyclase, which was as highly expressed as genes from a variety of well established biomarkers for melanoma, such as MAGE-3 and MART-1, which have frequently been used in clinical trials of melanoma vaccines [20].
  • Regularly tapped latexes also accumulated several low molecular weight proteins not yet identified, as well as three proteins identified as a trypsin inhibitor, a class-II chitinase and a glutaminyl cyclase on the basis of their enzymatic or inhibitory activities and chromatographic elution profiles [21].

Analytical, diagnostic and therapeutic context of QPCT


  1. Epigenetic silencing of novel tumor suppressors in malignant melanoma. Muthusamy, V., Duraisamy, S., Bradbury, C.M., Hobbs, C., Curley, D.P., Nelson, B., Bosenberg, M. Cancer Res. (2006) [Pubmed]
  2. Heterologous expression and characterization of human glutaminyl cyclase: evidence for a disulfide bond with importance for catalytic activity. Schilling, S., Hoffmann, T., Rosche, F., Manhart, S., Wasternack, C., Demuth, H.U. Biochemistry (2002) [Pubmed]
  3. Relationship between parental trinucleotide GCT repeat length and severity of myotonic dystrophy in offspring. Redman, J.B., Fenwick, R.G., Fu, Y.H., Pizzuti, A., Caskey, C.T. JAMA (1993) [Pubmed]
  4. Triplet repeat polymorphism in the transmembrane region of the MICA gene: a strong association of six GCT repetitions with Behçet disease. Mizuki, N., Ota, M., Kimura, M., Ohno, S., Ando, H., Katsuyama, Y., Yamazaki, M., Watanabe, K., Goto, K., Nakamura, S., Bahram, S., Inoko, H. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  5. Human cell lines that elaborate colon-stimulating activity for the marrow cells of man and other species. Di Persio, J.F., Brennan, J.K., Lichtman, M.A., Speiser, B.L. Blood (1978) [Pubmed]
  6. Crystal structures of human glutaminyl cyclase, an enzyme responsible for protein N-terminal pyroglutamate formation. Huang, K.F., Liu, Y.L., Cheng, W.J., Ko, T.P., Wang, A.H. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  7. Combination chemotherapy with gemcitabine plus oxaliplatin in patients with intensively pretreated or refractory germ cell cancer: a study of the German Testicular Cancer Study Group. Kollmannsberger, C., Beyer, J., Liersch, R., Schoeffski, P., Metzner, B., Hartmann, J.T., Rick, O., Stengele, K., Hohloch, K., Spott, C., Kanz, L., Bokemeyer, C. J. Clin. Oncol. (2004) [Pubmed]
  8. Negative cooperativity of substrate binding but not enzyme activity in wild-type and mutant forms of CTP:glycerol-3-phosphate cytidylyltransferase. Sanker, S., Campbell, H.A., Kent, C. J. Biol. Chem. (2001) [Pubmed]
  9. Hepatocytic transcription factor expression in human embryonal carcinoma and yolk sac carcinoma cell lines: expression of HNF-3 alpha in models of early endodermal cell differentiation. Roach, S., Schmid, W., Pera, M.F. Exp. Cell Res. (1994) [Pubmed]
  10. Two missense mutations causing tyrosinemia type 1 with presence and absence of immunoreactive fumarylacetoacetase. Rootwelt, H., Chou, J., Gahl, W.A., Berger, R., Coşkun, T., Brodtkorb, E., Kvittingen, E.A. Hum. Genet. (1994) [Pubmed]
  11. Seladin-1/DHCR24 expression in normal ovary, ovarian epithelial and granulosa tumours. Fuller, P.J., Alexiadis, M., Jobling, T., McNeilage, J. Clin. Endocrinol. (Oxf) (2005) [Pubmed]
  12. Association of multiple nucleotide variations in the pituitary glutaminyl cyclase gene (QPCT) with low radial BMD in adult women. Ezura, Y., Kajita, M., Ishida, R., Yoshida, S., Yoshida, H., Suzuki, T., Hosoi, T., Inoue, S., Shiraki, M., Orimo, H., Emi, M. J. Bone Miner. Res. (2004) [Pubmed]
  13. Evidence for essential histidines in human pituitary glutaminyl cyclase. Bateman, R.C., Temple, J.S., Misquitta, S.A., Booth, R.E. Biochemistry (2001) [Pubmed]
  14. Molecular cloning, sequence analysis and expression of human pituitary glutaminyl cyclase. Song, I., Chuang, C.Z., Bateman, R.C. J. Mol. Endocrinol. (1994) [Pubmed]
  15. The fractionation, characterization, and subcellular localization of colony-stimulating activities released by the human monocyte-like cell line, GCT. DiPersio, J.F., Brennan, J.K., Lichtman, M.A., Abboud, C.N., Kirkpatrick, F.H. Blood (1980) [Pubmed]
  16. Biological characterization of a granulomonopoietic enhancing activity derived from cultured human lipid-containing macrophages. Wang, S.Y., Castro-Malaspina, H., Lu, L., Moore, M.A. Blood (1985) [Pubmed]
  17. Monocyte-macrophage-derived acidic isoferritins: normal feedback regulators of granulocyte-macrophage progenitor cells in vitro. Broxmeyer, H.E., Bognacki, J., Ralph, P., Dörner, M.H., Lu, L., Castro-Malaspina, H. Blood (1982) [Pubmed]
  18. Autostimulation of growth by human myelogenous leukemia cells (HL-60). Brennan, J.K., Abboud, C.N., DiPersio, J.F., Barlow, G.H., Lichtman, M.A. Blood (1981) [Pubmed]
  19. Identification of human glutaminyl cyclase as a metalloenzyme. Potent inhibition by imidazole derivatives and heterocyclic chelators. Schilling, S., Niestroj, A.J., Rahfeld, J.U., Hoffmann, T., Wermann, M., Zunkel, K., Wasternack, C., Demuth, H.U. J. Biol. Chem. (2003) [Pubmed]
  20. Microarray evidence of glutaminyl cyclase gene expression in melanoma: implications for tumor antigen specific immunotherapy. Gillis, J.S. Journal of translational medicine [electronic resource]. (2006) [Pubmed]
  21. Detection of three wound-induced proteins in papaya latex. Azarkan, M., Wintjens, R., Looze, Y., Baeyens-Volant, D. Phytochemistry (2004) [Pubmed]
  22. A general strategy for random insertion and substitution mutagenesis: substoichiometric coupling of trinucleotide phosphoramidites. Sondek, J., Shortle, D. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  23. Clinical impact of germ cell tumor cells in apheresis products of patients receiving high-dose chemotherapy. Bokemeyer, C., Gillis, A.J., Pompe, K., Mayer, F., Metzner, B., Schleucher, N., Schleicher, J., Pflugrad-Jauch, G., Oosterhuis, J.W., Kanz, L., Looijenga, L.H. J. Clin. Oncol. (2001) [Pubmed]
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