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Gene Review

PRKG1  -  protein kinase, cGMP-dependent, type I

Homo sapiens

Synonyms: AAT8, PGK, PKG, PRKG1B, PRKGR1A, ...
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Disease relevance of PRKG1

  • The association between C2276T polymorphism in PRKG1 gene and obesity was tested using linear regression analysis [1].
  • To determine whether Langerhans' histiocytosis is a polyclonal reactive disease or a clonal disorder, we used X-linked polymorphic DNA probes (HUMARA, PGK, M27 beta[DXS255], and HPRT) to assess clonality in lesional tissues and control leukocytes from 10 female patients with various forms of the disease [2].
  • Recombination frequencies of 0%-4% were found between choroideremia and five markers (PGK, DXS3, DXYS12, DXS72, and DXYS1) located in Xq13-22 [3].
  • We used human immunodeficiency virus type-1 (HIV-1)-based vectors expressing enhanced green fluorescent protein (EGFP) driven by different promoters (CMV, MPSV, or PGK) and investigated their ability to transduce human T- and B-cell lines, as well as resting or activated primary peripheral and umbilical cord blood lymphocytes [4].
  • Specimens from 10 fibroadenomas and 5 phyllodes tumors heterozygous for the BstXI polymorphism of PGK gene were subjected to clonal analysis [5].

High impact information on PRKG1

  • Analysis of mouse-human hybrids with the relevant chromosome provides evidence that the derepressed locus is on the inactive X, and that reactivation is not extensive (the PGK locus is not derepressed) [6].
  • We therefore analysed X-chromosome inactivation patterns with differential methylation patterns of heterozygotes for three DNA probes, HPRT, PGK, and M27 beta, in leukaemic patients and normal controls [7].
  • Data obtained using this assay correlated substantially with those obtained using the PGK, HPRT, and M27 beta probes, which detect X inactivation patterns by Southern blot analysis [8].
  • The content of mRNA in the variant fibroblasts was compared to that of normal cells by the semiquantitative dot hybridization method, and, more accurately, by the liquid hybridization method, using a human PGK cDNA as a probe [9].
  • Microsatellite polymerase chain reaction (PCR) and PCR analysis of PGK gene methylation have been used to study highly purified populations of peripheral blood cells [10].

Chemical compound and disease context of PRKG1


Biological context of PRKG1


Anatomical context of PRKG1

  • In contrast, human cGKIbeta mRNA (7.0 kb) was detected abundantly only in the uterus [13].
  • Three different second-generation lentiviral self-inactivating vectors containing CMV, EF1alpha and PGK promoter, respectively, and all carrying the exogenous GFP gene, were compared for expression in human B-cell precursor ALL blasts [15].
  • Substituting the CAG promoter for PGK in lentiviral constructs enhanced transgene expression in DC and EBV-B cells, amplifying T cell recognition [16].
  • Plasmid DNA containing factor VIII or factor IX minigenes and driven by three human cellular promoters (albumin, factor IX, PGK) or the strong viral promoter RSV-LTR were electroporated into TE671 and HepG2 cell lines, and clotting factor levels were determined by ELISA [17].
  • The Ad5F35-GFP vector-mediated gene transfer efficiency was compared with a fiber non-modified Ad5-GFP vector, which also encodes the GFP gene under the control of the PGK promoter [18].

Associations of PRKG1 with chemical compounds

  • Mutation of these four serines to alanine showed that cGKIbeta-dependent phosphorylation of Ser(696) is necessary to decrease calcium release from InsP(3)-sensitive stores [19].
  • For the type I cGMP-dependent protein kinases (cGKIalpha and cGKIbeta), a high affinity interaction exists between the C2 amino group of cGMP and the hydroxyl side chain of a threonine conserved in most cGMP binding sites [20].
  • Immunological analysis of cyanogen bromide digests of SmPGK with monoclonal antibodies that recognize SmPGK but not human PGK identifies a B-cell epitope on a 12.2-kDa fragment represented by amino acids 61 to 174 [21].
  • Human PGK demonstrated catalytic efficiencies in the 10(4)-10(5)M(-1)s(-1) range for purine ribo-, deoxyribo- and dideoxyribonucleotide derivatives, either in D- or L-configuration [22].
  • In the present work, we extended the enzymatic study of human PGK specificity to purine and pyrimidine nucleotide derivatives in both D- and L-configuration [22].

Physical interactions of PRKG1

  • IRAG is present in a macromolecular complex with the InsP(3) receptor type I (InsP(3)RI) and cGKIbeta [19].

Other interactions of PRKG1

  • The protein kinase cGMP-dependent, type I (PRKG1) and the TBP genes were expressed at common abundance and exhibited the lowest variability among the cell specimens [23].
  • These results show that cGMP induced reduction of cytosolic calcium concentrations requires cGKIbeta and phosphorylation of Ser(696) of IRAG [19].
  • Finally, we present evidence that the dominant negative properties of this truncation mutant are specific to cGKII when compared with cAMP-dependent protein kinase Calpha and cGKIbeta [24].

Analytical, diagnostic and therapeutic context of PRKG1

  • In four patients, three of whom were already studied by Southern analyses of genomic DNA and one in whom there were insufficient amounts of DNA, polymerase chain reaction (PCR)-based clonal analysis was performed with primer pairs flanking the BstXI polymorphism on the PGK gene [25].
  • We used WAS-/- mice to test the efficacy of a gene therapy approach based on nonlethal irradiation followed by transplantation of WAS-/- HSCs transduced with lentiviral vectors encoding the WAS protein (WASP) from either the ubiquitous PGK promoter or the tissue- specific WAS promoter [26].
  • Thus, during natural infection antibodies that cross-react with human PGK are not produced; however, as a result of active immunization with an intact conserved molecule, such cross-reacting antibodies are produced [21].
  • RT-PCR analysis identified this aberrant transcript as arising from the antisense strand of the PGK promoter [27].


  1. Lack of association between polymorphism of the human cyclic GMP-dependent protein kinase gene and obesity. Zakharkin, S.O., Belay, A.T., Fernandez, J.R., De Luca, V., Kennedy, J.L., Sokolowski, M.B., Allison, D.B. International journal of obesity (2005) (2005) [Pubmed]
  2. Langerhans'-cell histiocytosis (histiocytosis X)--a clonal proliferative disease. Willman, C.L., Busque, L., Griffith, B.B., Favara, B.E., McClain, K.L., Duncan, M.H., Gilliland, D.G. N. Engl. J. Med. (1994) [Pubmed]
  3. Multipoint linkage analysis of loci in the proximal long arm of the human X chromosome: application to mapping the choroideremia locus. Lesko, J.G., Lewis, R.A., Nussbaum, R.L. Am. J. Hum. Genet. (1987) [Pubmed]
  4. Lentiviral-mediated gene transfer into human lymphocytes: role of HIV-1 accessory proteins. Chinnasamy, D., Chinnasamy, N., Enriquez, M.J., Otsu, M., Morgan, R.A., Candotti, F. Blood (2000) [Pubmed]
  5. Clonal analysis of fibroadenoma and phyllodes tumor of the breast. Noguchi, S., Motomura, K., Inaji, H., Imaoka, S., Koyama, H. Cancer Res. (1993) [Pubmed]
  6. Derepression with decreased expression of the G6PD locus on the inactive X chromosome in normal human cells. Migeon, B.R., Wolf, S.F., Mareni, C., Axelman, J. Cell (1982) [Pubmed]
  7. Frequency of clonal remission in acute myeloid leukaemia. Gale, R.E., Wheadon, H., Goldstone, A.H., Burnett, A.K., Linch, D.C. Lancet (1993) [Pubmed]
  8. Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. Allen, R.C., Zoghbi, H.Y., Moseley, A.B., Rosenblatt, H.M., Belmont, J.W. Am. J. Hum. Genet. (1992) [Pubmed]
  9. Normal mRNA content in a phosphoglycerate kinase variant with severe enzyme deficiency. Tani, K., Takizawa, T., Yoshida, A. Am. J. Hum. Genet. (1985) [Pubmed]
  10. Deletion of chromosome 20q in myelodysplasia can occur in a multipotent precursor of both myeloid cells and B cells. White, N.J., Nacheva, E., Asimakopoulos, F.A., Bloxham, D., Paul, B., Green, A.R. Blood (1994) [Pubmed]
  11. Characterization of the human gene encoding the type I alpha and type I beta cGMP-dependent protein kinase (PRKG1). Orstavik, S., Natarajan, V., Taskén, K., Jahnsen, T., Sandberg, M. Genomics (1997) [Pubmed]
  12. A drosophila model for attention deficit hyperactivity disorder (ADHD): No evidence of association with PRKG1 gene. De Luca, V., Muglia, P., Jain, U., Basile, V.S., Sokolowski, M.B., Kennedy, J.L. Neuromolecular Med. (2002) [Pubmed]
  13. cDNA cloning and gene expression of human type Ialpha cGMP-dependent protein kinase. Tamura, N., Itoh, H., Ogawa, Y., Nakagawa, O., Harada, M., Chun, T.H., Suga, S., Yoshimasa, T., Nakao, K. Hypertension (1996) [Pubmed]
  14. Localization of the human gene for the type I cyclic GMP-dependent protein kinase to chromosome 10. Orstavik, S., Sandberg, M., Bérubé, D., Natarajan, V., Simard, J., Walter, U., Gagné, R., Hansson, V., Jahnsen, T. Cytogenet. Cell Genet. (1992) [Pubmed]
  15. Functional transfer of CD40L gene in human B-cell precursor ALL blasts by second-generation SIN lentivectors. Bonamino, M., Serafini, M., D'Amico, G., Gaipa, G., Todisco, E., Bernasconi, S., Golay, J., Biondi, A., Introna, M. Gene Ther. (2004) [Pubmed]
  16. Lentivirus vector-mediated expression of tumor-associated epitopes by human antigen presenting cells. Lizée, G., Gonzales, M.I., Topalian, S.L. Hum. Gene Ther. (2004) [Pubmed]
  17. Production of minigene-containing retroviral vectors using an alphavirus/retrovirus hybrid vector system. Wahlfors, J.J., Morgan, R.A. Hum. Gene Ther. (1999) [Pubmed]
  18. Development of an adenoviral vector system with adenovirus serotype 35 tropism; efficient transient gene transfer into primary malignant hematopoietic cells. Nilsson, M., Ljungberg, J., Richter, J., Kiefer, T., Magnusson, M., Lieber, A., Widegren, B., Karlsson, S., Fan, X. The journal of gene medicine. (2004) [Pubmed]
  19. Molecular determinants of the interaction between the inositol 1,4,5-trisphosphate receptor-associated cGMP kinase substrate (IRAG) and cGMP kinase Ibeta. Ammendola, A., Geiselhöringer, A., Hofmann, F., Schlossmann, J. J. Biol. Chem. (2001) [Pubmed]
  20. The amino-terminal cyclic nucleotide binding site of the type II cGMP-dependent protein kinase is essential for full cyclic nucleotide-dependent activation. Taylor, M.K., Uhler, M.D. J. Biol. Chem. (2000) [Pubmed]
  21. Immune response to Schistosoma mansoni phosphoglycerate kinase during natural and experimental infection: identification of a schistosome-specific B-cell epitope. Lee, K.W., Thakur, A., Karim, A.M., LoVerde, P.T. Infect. Immun. (1995) [Pubmed]
  22. Broad specificity of human phosphoglycerate kinase for antiviral nucleoside analogs. Gallois-Montbrun, S., Faraj, A., Seclaman, E., Sommadossi, J.P., Deville-Bonne, D., Véron, M. Biochem. Pharmacol. (2004) [Pubmed]
  23. Optimization of quantitative real-time RT-PCR parameters for the study of lymphoid malignancies. Lossos, I.S., Czerwinski, D.K., Wechser, M.A., Levy, R. Leukemia (2003) [Pubmed]
  24. Autoinhibition and isoform-specific dominant negative inhibition of the type II cGMP-dependent protein kinase. Taylor, M.K., Ahmed, R., Begley, M., Uhler, M.D. J. Biol. Chem. (2002) [Pubmed]
  25. Clonal studies of CD3- lymphoproliferative disease of granular lymphocytes. Nash, R., McSweeney, P., Zambello, R., Semenzato, G., Loughran, T.P. Blood (1993) [Pubmed]
  26. Efficacy of gene therapy for Wiskott-Aldrich syndrome using a WAS promoter/cDNA-containing lentiviral vector and nonlethal irradiation. Dupré, L., Marangoni, F., Scaramuzza, S., Trifari, S., Hernández, R.J., Aiuti, A., Naldini, L., Roncarolo, M.G. Hum. Gene Ther. (2006) [Pubmed]
  27. Bidirectional transcriptional activity of PGK-neomycin and unexpected embryonic lethality in heterozygote chimeric knockout mice. Scacheri, P.C., Crabtree, J.S., Novotny, E.A., Garrett-Beal, L., Chen, A., Edgemon, K.A., Marx, S.J., Spiegel, A.M., Chandrasekharappa, S.C., Collins, F.S. Genesis (2001) [Pubmed]
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