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Gene Review

PPIG  -  peptidylprolyl isomerase G (cyclophilin G)

Homo sapiens

Synonyms: CARS-Cyp, CARS-cyclophilin, CASP10, CYP, Clk-associating RS-cyclophilin, ...
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Disease relevance of PPIG


Psychiatry related information on PPIG

  • Variability of alimentary CYP expression may contribute to individual differences in susceptibility to carcinogens and/or drugs [6].

High impact information on PPIG

  • Divergent approaches, including kinetic modeling and X-ray crystallography, are providing new information about how multiple ligand binding yields complex CYP kinetics [7].
  • However, as it is possible that human CYP 1A2 may also be inducible by these same chemicals (because of the possible presence of an ARE in this gene), the ultimate consequence of dietary treatment with chemicals that induce biotransformation enzymes via an ARE is uncertain [8].
  • The role of a 150-kD SR-cyclophilin (NK-TR1) in monocyte differentiation was investigated [9].
  • Association of the expression of an SR-cyclophilin with myeloid cell differentiation [9].
  • This indicates that factors affecting CYP 2E1 metabolism exerted a greater role on production of 1,4-BQ than BO, presumably because of the second oxidation step from phenol to hydroquinone [10].

Chemical compound and disease context of PPIG


Biological context of PPIG

  • SR-cyp might direct its effect via either alteration of protein folding/conformation or of protein-protein interaction and thus may add another control level of regulation of SR family proteins and modification of their functions [16].
  • Only in late telophase is SRcyp recruited to the newly formed nuclei [17].
  • We report here the identification of five Cdc2-type phosphorylation sites gathered in and around the moca domain of SRcyp, a human cyclophilin belonging to the Moca family [17].
  • The cytochrome P450 3A7 (CYP3A7) is the most abundant CYP in human liver during fetal development and first months of postnatal age, playing an important role in the metabolism of endogenous hormones, drugs, differentiation factors, and potentially toxic and teratogenic substrates [18].
  • The human P450IIB gene has been located to chromosome 19q12----19q13.2 using a probe derived from intron 5, and is close to the CYP 2A locus encoding cytochrome P450IIA2 [19].

Anatomical context of PPIG

  • These results indicate that carcinogen activation by CYP enzymes expressed in the gastric mucosa may contribute to carcinogenesis of the stomach [20].
  • A peptidyl-prolyl cis/trans-isomerase (cyclophilin G) in regulated secretory granules [21].
  • Clarithromycin, ketoconazole, and fluconazole inhibited CYP-mediated metabolism of rifabutin in enterocyte microsomes equally or more potently than in liver microsomes but had no effect on cholinesterase activity [22].
  • Microsomes enriched in each of these CYPs were obtained from commercial +/- lymphoblast cells that had been transfected with cDNA encoding the specific human CYP [23].
  • Finally, the identification of mutant alleles of the P-450IID1 gene (CYP 2D) by restriction fragment length polymorphisms in lymphocyte DNA of poor metabolizers is presented [24].

Associations of PPIG with chemical compounds

  • One explanation for the noted increase in the theophylline level is that metabolism occurs mainly by cytochrome P450 (CYP 1A2), an enzyme that is known to be inhibited with high concentrations of zafirlukast [25].
  • Efavirenz induces the metabolism of co-administered drugs through the induction of CYP A4 [26].
  • However, this possibility is at odds with previous clinical studies that showed that acute ethanol ingestion could protect against hepatotoxicity by inhibiting CYP-mediated acetaminophen oxidation [27].
  • A combined mephenytoin, sparteine, and caffeine test performed before, during, and after multiple dosing of moclobemide showed changes in the metabolic indexes compatible with a reversible inhibition of oxidation by way of the corresponding CYP enzymes--CYP2C19, CYP2D6, and CYP1A2--during moclobemide treatment [28].
  • The major pathways of arachidonic acid metabolism catalyzed by cytochrome P450 generate metabolites that are subdivided into two groups: the epoxyeicosatrienoic acids, formed by CYP epoxygenases, and the arachidonic acid derivatives that are hydroxylated at or near the omega-terminus by CYP omega-oxidases [29].

Other interactions of PPIG

  • Over-expression of SR-cyclophilin, an interaction partner of nuclear pinin, releases SR family splicing factors from nuclear speckles [16].

Analytical, diagnostic and therapeutic context of PPIG


  1. Genetic variability of the CYP 2D6 gene is not a risk factor for sporadic Parkinson's disease. Diederich, N., Hilger, C., Goetz, C.G., Keipes, M., Hentges, F., Vieregge, P., Metz, H. Ann. Neurol. (1996) [Pubmed]
  2. Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis. Huang, Y.S., Chern, H.D., Su, W.J., Wu, J.C., Chang, S.C., Chiang, C.H., Chang, F.Y., Lee, S.D. Hepatology (2003) [Pubmed]
  3. Retroviral transfer of human cytochrome P450 genes for oxazaphosphorine-based cancer gene therapy. Jounaidi, Y., Hecht, J.E., Waxman, D.J. Cancer Res. (1998) [Pubmed]
  4. Export of a heterologous cytochrome P450 (CYP105D1) in Escherichia coli is associated with periplasmic accumulation of uroporphyrin. Akhtar, M.K., Kaderbhai, N.N., Hopper, D.J., Kelly, S.L., Kaderbhai, M.A. J. Biol. Chem. (2003) [Pubmed]
  5. Cyclophilin D as a drug target. Waldmeier, P.C., Zimmermann, K., Qian, T., Tintelnot-Blomley, M., Lemasters, J.J. Current medicinal chemistry. (2003) [Pubmed]
  6. Expression of cytochrome P450 mRNAs in the colon and the rectum in normal human subjects. Mercurio, M.G., Shiff, S.J., Galbraith, R.A., Sassa, S. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  7. Non-Michaelis-Menten kinetics in cytochrome P450-catalyzed reactions. Atkins, W.M. Annu. Rev. Pharmacol. Toxicol. (2005) [Pubmed]
  8. Mechanisms of aflatoxin carcinogenesis. Eaton, D.L., Gallagher, E.P. Annu. Rev. Pharmacol. Toxicol. (1994) [Pubmed]
  9. Association of the expression of an SR-cyclophilin with myeloid cell differentiation. Giardina, S.L., Coffman, J.D., Young, H.A., Potter, S.J., Frey, J.L., Ortaldo, J.R., Anderson, S.K. Blood (1996) [Pubmed]
  10. Albumin adducts of benzene oxide and 1,4-benzoquinone as measures of human benzene metabolism. Rappaport, S.M., Waidyanatha, S., Qu, Q., Shore, R., Jin, X., Cohen, B., Chen, L.C., Melikian, A.A., Li, G., Yin, S., Yan, H., Xu, B., Mu, R., Li, Y., Zhang, X., Li, K. Cancer Res. (2002) [Pubmed]
  11. CYP1A in TCDD toxicity and in physiology-with particular reference to CYP dependent arachidonic acid metabolism and other endogenous substrates. Rifkind, A.B. Drug Metab. Rev. (2006) [Pubmed]
  12. Metabolism of the soyabean isoflavone daidzein by CYP1A2 and the extra-hepatic CYPs 1A1 and 1B1 affects biological activity. Atherton, K.M., Mutch, E., Ford, D. Biochem. Pharmacol. (2006) [Pubmed]
  13. Nicotine induces brain CYP enzymes: relevance to Parkinson's disease. Miksys, S., Tyndale, R.F. J. Neural Transm. Suppl. (2006) [Pubmed]
  14. Influence of chronic renal failure on stereoselective metoprolol metabolism in hypertensive patients. Cerqueira, P.M., Coelho, E.B., Geleilete, T.J., Goldman, G.H., Lanchote, V.L. Journal of clinical pharmacology. (2005) [Pubmed]
  15. Genetic polymorphism of CYP2A6 as one of the potential determinants of tobacco-related cancer risk. Kamataki, T., Fujieda, M., Kiyotani, K., Iwano, S., Kunitoh, H. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  16. Over-expression of SR-cyclophilin, an interaction partner of nuclear pinin, releases SR family splicing factors from nuclear speckles. Lin, C.L., Leu, S., Lu, M.C., Ouyang, P. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  17. The human nuclear SRcyp is a cell cycle-regulated cyclophilin. Dubourg, B., Kamphausen, T., Weiwad, M., Jahreis, G., Feunteun, J., Fischer, G., Modjtahedi, N. J. Biol. Chem. (2004) [Pubmed]
  18. A novel polymorphic cytochrome P450 formed by splicing of CYP3A7 and the pseudogene CYP3AP1. Rodriguez-Antona, C., Axelson, M., Otter, C., Rane, A., Ingelman-Sundberg, M. J. Biol. Chem. (2005) [Pubmed]
  19. A novel human cytochrome P450 gene (P450IIB): chromosomal localization and evidence for alternative splicing. Miles, J.S., Spurr, N.K., Gough, A.C., Jowett, T., McLaren, A.W., Brook, J.D., Wolf, C.R. Nucleic Acids Res. (1988) [Pubmed]
  20. Mutagenic activation of environmental carcinogens by microsomes of gastric mucosa with intestinal metaplasia. Tatemichi, M., Nomura, S., Ogura, T., Sone, H., Nagata, H., Esumi, H. Cancer Res. (1999) [Pubmed]
  21. A peptidyl-prolyl cis/trans-isomerase (cyclophilin G) in regulated secretory granules. Takaki, Y., Muta, T., Iwanaga, S. J. Biol. Chem. (1997) [Pubmed]
  22. Metabolism of rifabutin in human enterocyte and liver microsomes: kinetic parameters, identification of enzyme systems, and drug interactions with macrolides and antifungal agents. Iatsimirskaia, E., Tulebaev, S., Storozhuk, E., Utkin, I., Smith, D., Gerber, N., Koudriakova, T. Clin. Pharmacol. Ther. (1997) [Pubmed]
  23. Production of reactive oxygen species by microsomes enriched in specific human cytochrome P450 enzymes. Puntarulo, S., Cederbaum, A.I. Free Radic. Biol. Med. (1998) [Pubmed]
  24. The genetic polymorphism of debrisoquine/sparteine metabolism-molecular mechanisms. Meyer, U.A., Skoda, R.C., Zanger, U.M. Pharmacol. Ther. (1990) [Pubmed]
  25. A drug interaction between zafirlukast and theophylline. Katial, R.K., Stelzle, R.C., Bonner, M.W., Marino, M., Cantilena, L.R., Smith, L.J. Arch. Intern. Med. (1998) [Pubmed]
  26. Dose escalation or immediate full dose when switching from efavirenz to nevirapine-based highly active antiretroviral therapy in HIV-1-infected individuals? Winston, A., Pozniak, A., Smith, N., Fletcher, C., Mandalia, S., Parmar, D., Gibbons, S., Back, D., Gazzard, B., Nelson, M. AIDS (2004) [Pubmed]
  27. Ethanol and production of the hepatotoxic metabolite of acetaminophen in healthy adults. Thummel, K.E., Slattery, J.T., Ro, H., Chien, J.Y., Nelson, S.D., Lown, K.E., Watkins, P.B. Clin. Pharmacol. Ther. (2000) [Pubmed]
  28. Moclobemide, a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6, and CYP1A2: a panel study. Gram, L.F., Guentert, T.W., Grange, S., Vistisen, K., Brøsen, K. Clin. Pharmacol. Ther. (1995) [Pubmed]
  29. Role of cytochrome P450 in phospholipase A2- and arachidonic acid-mediated cytotoxicity. Caro, A.A., Cederbaum, A.I. Free Radic. Biol. Med. (2006) [Pubmed]
  30. Induction of CYP2E1 activity in liver transplant patients as measured by chlorzoxazone 6-hydroxylation. Burckart, G.J., Frye, R.F., Kelly, P., Branch, R.A., Jain, A., Fung, J.J., Starzl, T.E., Venkataramanan, R. Clin. Pharmacol. Ther. (1998) [Pubmed]
  31. Transcript profiling of enzymes involved in detoxification of xenobiotics and reactive oxygen in human normal and simian virus 40 T antigen-immortalized oral keratinocytes. Vondracek, M., Weaver, D.A., Sarang, Z., Hedberg, J.J., Willey, J.C., Wärngård, L., Grafström, R.C. Int. J. Cancer (2002) [Pubmed]
  32. CYP enzyme polymorphisms and susceptibility to HCV-related chronic liver disease and liver cancer. Silvestri, L., Sonzogni, L., De Silvestri, A., Gritti, C., Foti, L., Zavaglia, C., Leveri, M., Cividini, A., Mondelli, M.U., Civardi, E., Silini, E.M. Int. J. Cancer (2003) [Pubmed]
  33. Metabolic activation of pradefovir by CYP3A4 and its potential as an inhibitor or inducer. Lin, C.C., Fang, C., Benetton, S., Xu, G.F., Yeh, L.T. Antimicrob. Agents Chemother. (2006) [Pubmed]
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