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Gene Review

PDE7A  -  phosphodiesterase 7A

Homo sapiens

Synonyms: HCP1, High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A, PDE7, TM22
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Disease relevance of PDE7A

  • As treatment with the methylxanthine theophylline, a nonspecific PDE inhibitor, induces apoptosis in leukemic cells from patients with the B-lineage malignancy chronic lymphocytic leukemia (CLL), we sought to determine if PDE7A was a target of theophylline therapy in such cells [1].
  • Refolding and purification of recombinant human PDE7A expressed in Escherichia coli as inclusion bodies [2].
  • The development of dual-specificity compounds that inhibit PDE4 and PDE1, PDE3, PDE5 or PDE7 could be beneficial for the treatment of chronic inflammatory lung diseases and are currently being investigated [3].
  • Intestinal Hcp1 mRNA content was not significantly changed by iron overload (600 mg/kg); however, it was increased to 170 % of controls 72 h after withdrawal of 0.7 ml of blood; the same treatment increased intestinal Cybrd1 mRNA to 900 % of controls [4].

High impact information on PDE7A

  • Increased PDE7 in T cells correlated with decreased cAMP, increased interleukin-2 expression, and increased proliferation [5].
  • Induction of adenosine 3',5'-monophosphate (cAMP)-specific phosphodiesterase-7 (PDE7) was found to be a consequence of such costimulation [5].
  • Histone H3 phosphorylation and HCP-1 staining, which marks kinetochores, were reduced in the absence of either BIR-1 or AIR-2 [6].
  • The localization of HCP-4 to the centromere is dependent on the centromeric histone HCP-3; in addition, HCP-3 and HCP-4 are both required for localization of a CENP-F-like protein, HCP-1, indicating an ordered assembly pathway [7].
  • PDE7A and PDE7B exhibit the same general pattern of inhibitor specificity among the several drugs tested [8].

Biological context of PDE7A


Anatomical context of PDE7A

  • PDE7A is a recently described 3',5'-cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase (PDE) whose expression has been detected in T-cells [1].
  • PDE7A is expressed in human B-lymphocytes and is up-regulated by elevation of intracellular cAMP [1].
  • Immunoconfocal analyses showed that PDE7A was expressed in neutrophils and alveolar macrophages [11].
  • Western analysis revealed expression of PDE7A in normal human splenic B-cells, primary CLL cells, and in a CLL-derived cell line (WSU-CLL) [1].
  • The even distribution of PDE7A mRNA among fetal tissues and the relative abundance of its two mRNAs strongly suggest that the expression of PDE7A is regulated throughout development [9].

Associations of PDE7A with chemical compounds

  • A potent selective inhibitor of PDE4 (IC50 = 0.00031 microM), RP 73401, which did not effectively suppress PDE7A (IC50 > 10 microM), inhibited the Df- and anti-CD3 MoAb-stimulated responses only weakly, even at 10 microM [12].
  • HCP1 is a high affinity cAMP-specific PDE (Km = 0.2 microM) that does not share other properties of the cAMP-specific PDE family, i.e. extensive sequence homology to the Drosophila dunce cAMP PDE and sensitivity to rolipram and R020-1724 [13].
  • Benzothiadiazine 16, although less potent at PDE 7 (IC(50) = 25 microM), also showed a trend of selectivity toward PDE 3 and PDE 4 [14].
  • By in situ hybridization histochemistry we have determined the expression pattern of two newly described cAMP-specific phosphodiesterases families, PDE7 and PDE8, in several brain areas in control subjects [15].
  • The CD spectra of the polyheptapeptides TM-8, TM-15, and TM-22 show large increases in molar ellipticity at 220 nm on the addition of trifluoroethanol (helix-inducing solvent) to the benign buffer [16].

Other interactions of PDE7A

  • Further analysis of MTG/PDE association illustrated that PDE4A and PDE7A bind residues 1-344 of MTG16b [17].
  • Confocal analysis of HuT 78 cells stained with anti-PDE7A showed overlapping staining patterns with the Golgi marker GM130, suggesting that PDE7A is located in the Golgi [17].
  • Qualitative RT-PCR identified transcripts for PDE4A10, PDE4A7, PDE4B1, PDE4B2, PDE4D1, and PDE4D2 isoforms as well as transcripts for both PDE3B and PDE7A in T cells, monocytes, and macrophages in all subjects [18].
  • Interestingly, the relative V(max) value of recombinant PDE7B was half to one-third of recombinant PDE7A [19].
  • Further analysis by RT-PCR of the PDE4D and PDE7A splice variants gave different accumulation patterns which may indicate that differential splicing has a role in the regulation of these enzymes [20].

Analytical, diagnostic and therapeutic context of PDE7A

  • The staining pattern of PDE7A also showed similarity to the staining pattern of MTG, supporting the immunoprecipitation data and suggesting that MTG may interact with PDE7A in the Golgi [17].
  • Northern blot analysis indicates that high levels of HCP1 mRNA are present in human skeletal muscle [13].
  • The PDE7A1 (HCP1) isozyme is detected on Western blots as a band with an apparent mobility of 57 kDa, demonstrating that the previously isolated HCP1 cDNA encodes the full-length PDE7A1 protein [9].
  • The peptides TM-8, TM-15, and TM-22 were shown to be monomeric in both denaturant (8 M urea) and benign medium by gel-filtration high-performance liquid chromatography on TSK G2000 SW while peptides TM-29 and TM-36 were shown to be dimeric in benign medium both by gel-filtration and sedimentation equilibrium experiments [16].
  • Using quantitative real-time PCR, we examined the expression of Hcp1 and other intestinal iron-transporting proteins in male C57BL/6 mice with experimentally altered iron homeostasis [4].


  1. PDE7A is expressed in human B-lymphocytes and is up-regulated by elevation of intracellular cAMP. Lee, R., Wolda, S., Moon, E., Esselstyn, J., Hertel, C., Lerner, A. Cell. Signal. (2002) [Pubmed]
  2. Refolding and purification of recombinant human PDE7A expressed in Escherichia coli as inclusion bodies. Richter, W., Hermsdorf, T., Kronbach, T., Dettmer, D. Protein Expr. Purif. (2002) [Pubmed]
  3. Life after PDE4: overcoming adverse events with dual-specificity phosphodiesterase inhibitors. Giembycz, M.A. Current opinion in pharmacology. (2005) [Pubmed]
  4. Effect of lipopolysaccharide and bleeding on the expression of intestinal proteins involved in iron and haem transport. Krijt, J., Vokurka, M., Sefc, L., Duricov??, D., Necas, E. Folia Biol. (Praha) (2006) [Pubmed]
  5. CD3- and CD28-dependent induction of PDE7 required for T cell activation. Li, L., Yee, C., Beavo, J.A. Science (1999) [Pubmed]
  6. The survivin-like C. elegans BIR-1 protein acts with the Aurora-like kinase AIR-2 to affect chromosomes and the spindle midzone. Speliotes, E.K., Uren, A., Vaux, D., Horvitz, H.R. Mol. Cell (2000) [Pubmed]
  7. HCP-4, a CENP-C-like protein in Caenorhabditis elegans, is required for resolution of sister centromeres. Moore, L.L., Roth, M.B. J. Cell Biol. (2001) [Pubmed]
  8. Cloning and characterization of PDE7B, a cAMP-specific phosphodiesterase. Hetman, J.M., Soderling, S.H., Glavas, N.A., Beavo, J.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  9. Alternative splicing of the high affinity cAMP-specific phosphodiesterase (PDE7A) mRNA in human skeletal muscle and heart. Han, P., Zhu, X., Michaeli, T. J. Biol. Chem. (1997) [Pubmed]
  10. Assignment of the mouse Pde7A gene to the proximal region of chromosome 3 and of the human PDE7A gene to chromosome 8q13. Han, P., Fletcher, C.F., Copeland, N.G., Jenkins, N.A., Yaremko, L.M., Michaeli, T. Genomics (1998) [Pubmed]
  11. Ubiquitous expression of phosphodiesterase 7A in human proinflammatory and immune cells. Smith, S.J., Brookes-Fazakerley, S., Donnelly, L.E., Barnes, P.J., Barnette, M.S., Giembycz, M.A. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  12. Potential role of phosphodiesterase 7 in human T cell function: comparative effects of two phosphodiesterase inhibitors. Nakata, A., Ogawa, K., Sasaki, T., Koyama, N., Wada, K., Kotera, J., Kikkawa, H., Omori, K., Kaminuma, O. Clin. Exp. Immunol. (2002) [Pubmed]
  13. Isolation and characterization of a previously undetected human cAMP phosphodiesterase by complementation of cAMP phosphodiesterase-deficient Saccharomyces cerevisiae. Michaeli, T., Bloom, T.J., Martins, T., Loughney, K., Ferguson, K., Riggs, M., Rodgers, L., Beavo, J.A., Wigler, M. J. Biol. Chem. (1993) [Pubmed]
  14. Benzyl derivatives of 2,1,3-benzo- and benzothieno[3,2-a]thiadiazine 2,2-dioxides: first phosphodiesterase 7 inhibitors. Martínez, A., Castro, A., Gil, C., Miralpeix, M., Segarra, V., Doménech, T., Beleta, J., Palacios, J.M., Ryder, H., Miró, X., Bonet, C., Casacuberta, J.M., Azorín, F., Piña, B., Puigdoménech, P. J. Med. Chem. (2000) [Pubmed]
  15. Alterations on phosphodiesterase type 7 and 8 isozyme mRNA expression in Alzheimer's disease brains examined by in situ hybridization. Pérez-Torres, S., Cortés, R., Tolnay, M., Probst, A., Palacios, J.M., Mengod, G. Exp. Neurol. (2003) [Pubmed]
  16. Synthesis of a model protein of defined secondary and quaternary structure. Effect of chain length on the stabilization and formation of two-stranded alpha-helical coiled-coils. Lau, S.Y., Taneja, A.K., Hodges, R.S. J. Biol. Chem. (1984) [Pubmed]
  17. A-kinase anchoring proteins interact with phosphodiesterases in T lymphocyte cell lines. Asirvatham, A.L., Galligan, S.G., Schillace, R.V., Davey, M.P., Vasta, V., Beavo, J.A., Carr, D.W. J. Immunol. (2004) [Pubmed]
  18. Differential expression of PDE4 cAMP phosphodiesterase isoforms in inflammatory cells of smokers with COPD, smokers without COPD, and nonsmokers. Barber, R., Baillie, G.S., Bergmann, R., Shepherd, M.C., Sepper, R., Houslay, M.D., Heeke, G.V. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  19. Identification of human PDE7B, a cAMP-specific phosphodiesterase. Sasaki, T., Kotera, J., Yuasa, K., Omori, K. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  20. Phosphodiesterases 4D and 7A splice variants in the response of HUVEC cells to TNF-alpha(1). Miró, X., Casacuberta, J.M., Gutiérrez-López, M.D., de Landázuri, M.O., Puigdomènech, P. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
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