Property Summary

NCBI Gene PubMed Count 54
PubMed Score 1167.78
PubTator Score 691.34

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (4)

Expression

  Differential Expression (16)

Disease log2 FC p
malignant mesothelioma 1.800 2.9e-07
astrocytic glioma -1.100 1.7e-03
psoriasis -1.700 2.0e-04
glioblastoma -1.600 5.1e-03
osteosarcoma -1.020 2.0e-02
ependymoma -1.400 1.3e-08
group 3 medulloblastoma -3.100 5.0e-07
atypical teratoid / rhabdoid tumor -1.700 2.8e-04
medulloblastoma, large-cell -3.200 2.7e-06
primitive neuroectodermal tumor -2.100 1.2e-04
adrenocortical carcinoma -1.128 4.2e-03
tuberculosis -1.200 1.4e-05
fibroadenoma -1.100 4.0e-02
adult high grade glioma -1.600 2.4e-04
invasive ductal carcinoma -1.100 3.1e-02
ovarian cancer 1.300 2.0e-03

 MGI Phenotype (1)

 GWAS Trait (1)

Gene RIF (41)

PMID Text
25576684 After 48 h yessotoxin treatment PDE4A-dependent autophagy, as non-apoptotic programmed cell death, is activated.
25230992 curcumin exerts its in vitro anti-angiogenic and in vivo anti-tumour properties through combined PDE2 and PDE4 inhibition
24813785 AKAP 149-PKA-PDE4A complex localization is related with YTX effect in K-562 cell line
24732776 Cyclic AMP phosphodiesterase inhibitors AV411 and AV1013 inhibit HIV-1 replication and block HIV-1 Tat-induced neurotoxicity in human microglia, suggesting that cyclic AMP phosphodiesterase is involved in the Tat-mediated neurotoxicity
24616094 Hydroxycarbamide decreases sickle reticulocyte adhesion to resting endothelium by inhibiting endothelial lutheran/basal cell adhesion molecule (Lu/BCAM) through phosphodiesterase 4A activation.
24227907 long-acting beta -agonist and PDE4 inhibitor have a synergistic effect in regulating fibroblast tissue repair functions and PGE2 can modulate the effect of beta -agonist and PDE4 inhibitor at least in part through the mechanism of regulating PDE4 expression
23043089 PDE4A and PDE4C work in redundant fashion to mediate the loss of inhibitory PGE2 signaling in lung fibroblasts.
23008439 In phosphoinositide 3-kinasegamma-deficient cardiomyocytes, coincident signaling of the major cardiac PDE3 and PDE4 isoforms orchestrates a feedback loop that prevents calcium-dependent ventricular arrhythmia.
22484154 The hPDE4 long isoforms are activated by phosphorylation of a serine located in a conserved RRESF motif in a tandem of N-terminal upstream-conserved regions (UCR).
21898905 These results indicate that PDE4A and PLAT may be susceptibility genes for schizophrenia in the Japanese population.
21732365 Data demonstrate that upregulation of Nox4 leads to an upregulation of PDE4A, B, and D and increased hydrolysis of cAMP which in turn augments cell replication and angiogenesis.
21652625 we have identified a so-far-unknown interaction between LIS1 and PDE4 isoforms, whereby PDE4 can modulate LIS1-dynein complexes and dynein-dependent processes within cells by sequestering LIS1.
21161247 PDE4 expression is reduced in failing human heart. PDE4 affects local but not global cAMP levels in human cardiomyocytes.
20813835 The results of this study suggested that apPDE4s can participate in the regulation of cAMP signaling through specific subcellular localization by means of lipid binding activities.
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20554760 Data show that inhibition of PA hydrolysis provokes internalization of inactive EGFR, accompanied by a transient increase in PA levels and PDE4s activity.
20193079 GSK256066 demonstrated a protective effect on the EAR and LAR.
20086095 Data show that PI3K activation and PIP3 production lead to recruitment of the PKB/beta-arrestin/PDE4 complex to the membrane via the PKB PH domain, resulting in degradation of the TCR-induced cAMP pool and allowing full T-cell activation to proceed.
20082309 Inhibition of PDE4 inhibition (rather than PDE3) may diminish proliferation of human lung fibroblasts and therefore could be useful in the therapy of pathological remodeling in lung diseases.
19913121 Observational study of gene-disease association. (HuGE Navigator)
19759179 Results suggest that TGF-beta1 mediated up-regulation of phosphodiesterase 4 promotes epithelial-mesenchymal transition in alveolar epithelial cells.
19642024 The results suggest that brain-derived neurotrophic factor/TrkB and cAMP phosphodiesterase-4, but not the gastrin-releasing peptide receptor, regulate the viability of medulloblastoma cells.
19047098 PDE4 is widely expressed in brain tumors and promotes their growth
19018233 observed that specific isoforms of PDE4A were reduced in cerebella of patients with bipolar disorder, whereas there was no change in patients with schizophrenia or major depression
18095939 unique tissue distribution of PDE4A8, combined with the evolutionary divergence of its N-terminus, suggest that this isoform may have a specific function in regulating cAMP levels in human skeletal muscle and brain
17576803 PDE4A4 interacts with the p75 neurotropin receptor to enhance cAMP degradation and block fibrinolysis by down-regulating tissue plasminogen activator and so perpetuating scar formation after sciatic nerve and lung injury
16940352 The unique N-terminal region of PDE4A1 consists of two helices, where Helix-1 regulates the phospholipase-D-dependent redistribution of PDE4A1 in response to release of Ca2+, providing a unique link between these signalling pathways
16856845 The N-terminal region unique to PDE4A1 consists of two well-defined helical regions separated by a mobile hinge region. Helix-2 provides the core membrane-insertion module and helix-1 facilitates membrane association.
16300476 In this review, the fundamental biological role of PDE4 in intracellular signalling, its tissue distribution and regulation are described.
16257373 Keynote review: phosphodiesterase-4 as a therapeutic target
15738310 PDE4A11 is a novel, widely expressed long isoform that is activated by protein kinase A phosphorylation, shows a distinct intracellular localization, and may contribute to compartmentalized cyclic AMP signaling in cells in which it is expressed.
15047569 PDE4A4 is specifically up-regulated in macrophages from smokers with chronic obstructive pulmonary disease (COPD) and may provide a specific therapeutic target.
12810716 The immunophilin AIP (XAP2/ARA9) reversibly inhibited the enzymatic activity of PDE4A5, an isoform of PDE4A.
12764607 Results suggest that type 4A cAMP-specific phosphodiesterase may downregulate cyclic AMP signaling at the cell membrane and/or in the extracellular space at the time of granule release.
11994273 An 11-residue helical module in the N-terminal region of PDE4A1 determines the association with phospholipid bilayers and shows a profound selectivity for interaction with phosphatidic acid.
11852080 In vitro phosphorylation of PDE4A4 by the PKA-catalytic subunit increases the enzyme's sensitivity to Mg(2+), leading to 4-fold increased cAMP hydrolysis without affecting its K(m).
11839681 Inhibition of PDE3B augments PDE4 inhibitor-induced apoptosis in a subset of patients with chronic lymphocytic leukemia
11566027 purification and characterization of recombinant proteins from E coli and Sf9 cells
11306681 PDE4A10 is a long form splice variant of the human cAMP phosphodiesterase PDE4A gene. PDE4A10 was localized primarily to the perinuclear region of COS7 cells.
11156964 Cyclic AMP phosphodiesterase inhibitors AV411 and AV1013 inhibit HIV-1 replication and block HIV-1 Tat-induced neurotoxicity in human microglia, suggesting that cyclic AMP phosphodiesterase is involved in the Tat-mediated neurotoxicity
11114167 Cyclic AMP phosphodiesterase inhibitors AV411 and AV1013 inhibit HIV-1 replication and block HIV-1 Tat-induced neurotoxicity in human microglia, suggesting that cyclic AMP phosphodiesterase is involved in the Tat-mediated neurotoxicity

AA Sequence

MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERAERERQPHRPIERADA      1 - 70
MDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRRFEAENGPTPSPGRSPLDSQASPGLVLHAGAATS     71 - 140
QRRESFLYRSDSDYDMSPKTMSRNSSVTSEAHAEDLIVTPFAQVLASLRSVRSNFSLLTNVPVPSNKRSP    141 - 210
LGGPTPVCKATLSEETCQQLARETLEELDWCLEQLETMQTYRSVSEMASHKFKRMLNRELTHLSEMSRSG    211 - 280
NQVSEYISTTFLDKQNEVEIPSPTMKEREKQQAPRPRPSQPPPPPVPHLQPMSQITGLKKLMHSNSLNNS    281 - 350
NIPRFGVKTDQEELLAQELENLNKWGLNIFCVSDYAGGRSLTCIMYMIFQERDLLKKFRIPVDTMVTYML    351 - 420
TLEDHYHADVAYHNSLHAADVLQSTHVLLATPALDAVFTDLEILAALFAAAIHDVDHPGVSNQFLINTNS    421 - 490
ELALMYNDESVLENHHLAVGFKLLQEDNCDIFQNLSKRQRQSLRKMVIDMVLATDMSKHMTLLADLKTMV    491 - 560
ETKKVTSSGVLLLDNYSDRIQVLRNMVHCADLSNPTKPLELYRQWTDRIMAEFFQQGDRERERGMEISPM    561 - 630
CDKHTASVEKSQVGFIDYIVHPLWETWADLVHPDAQEILDTLEDNRDWYYSAIRQSPSPPPEEESRGPGH    631 - 700
PPLPDKFQFELTLEEEEEEEISMAQIPCTAQEALTAQGLSGVEEALDATIAWEASPAQESLEVMAQEASL    701 - 770
EAELEAVYLTQQAQSTGSAPVAPDEFSSREEFVVAVSHSSPSALALQSPLLPAWRTLSVSEHAPGLPGLP    771 - 840
STAAEVEAQREHQAAKRACSACAGTFGEDTSALPAPGGGGSGGDPT                            841 - 886
//

Text Mined References (60)

PMID Year Title
25576684 2015 Key role of phosphodiesterase 4A (PDE4A) in autophagy triggered by yessotoxin.
25230992 2015 Tumour growth inhibition and anti-angiogenic effects using curcumin correspond to combined PDE2 and PDE4 inhibition.
24813785 2014 Role of AKAP 149-PKA-PDE4A complex in cell survival and cell differentiation processes.
24616094 2014 Hydroxycarbamide decreases sickle reticulocyte adhesion to resting endothelium by inhibiting endothelial lutheran/basal cell adhesion molecule (Lu/BCAM) through phosphodiesterase 4A activation.
24227907 2013 PGE 2 desensitizes ? -agonist effect on human lung fibroblast-mediated collagen gel contraction through upregulating PDE4.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23043089 2012 Attenuation of inhibitory prostaglandin E2 signaling in human lung fibroblasts is mediated by phosphodiesterase 4.
23008439 2012 Phosphoinositide 3-kinase ? protects against catecholamine-induced ventricular arrhythmia through protein kinase A-mediated regulation of distinct phosphodiesterases.
22484154 2012 The regulatory tandem domains of human phosphodiesterases 1 and 4 regulate a cyanobacterial adenylyl cyclase.
21898905 2011 Positive association of phencyclidine-responsive genes, PDE4A and PLAT, with schizophrenia.
21732365 2012 NADPH oxidase 4 mediates upregulation of type 4 phosphodiesterases in human endothelial cells.
21652625 2011 Interaction between LIS1 and PDE4, and its role in cytoplasmic dynein function.
21161247 2011 Conserved expression and functions of PDE4 in rodent and human heart.
20813835 2010 N termini of apPDE4 isoforms are responsible for targeting the isoforms to different cellular membranes.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20554760 2010 Phosphatidic acid induces ligand-independent epidermal growth factor receptor endocytic traffic through PDE4 activation.
20196770 2010 Selective SUMO modification of cAMP-specific phosphodiesterase-4D5 (PDE4D5) regulates the functional consequences of phosphorylation by PKA and ERK.
20193079 2010 The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma.
20086095 2010 Cross talk between phosphatidylinositol 3-kinase and cyclic AMP (cAMP)-protein kinase a signaling pathways at the level of a protein kinase B/beta-arrestin/cAMP phosphodiesterase 4 complex.
20082309 2010 Cytokine-dependent balance of mitogenic effects in primary human lung fibroblasts related to cyclic AMP signaling and phosphodiesterase 4 inhibition.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19759179 2009 Expression and activity of phosphodiesterase isoforms during epithelial mesenchymal transition: the role of phosphodiesterase 4.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19642024 2010 BDNF and PDE4, but not the GRPR, regulate viability of human medulloblastoma cells.
19047098 2008 Targeted inhibition of cyclic AMP phosphodiesterase-4 promotes brain tumor regression.
19018233 2008 Phosphodiesterase-4A expression is reduced in cerebella of patients with bipolar disorder.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18095939 2008 Human PDE4A8, a novel brain-expressed PDE4 cAMP-specific phosphodiesterase that has undergone rapid evolutionary change.
17727341 2007 Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors.
17704206 2007 Differential regulation of endothelial cell permeability by cGMP via phosphodiesterases 2 and 3.
17576803 2007 p75 neurotrophin receptor regulates tissue fibrosis through inhibition of plasminogen activation via a PDE4/cAMP/PKA pathway.
17404263 2007 Differential expression and function of phosphodiesterase 4 (PDE4) subtypes in human primary CD4+ T cells: predominant role of PDE4D.
16940352 2006 Helix-1 of the cAMP-specific phosphodiesterase PDE4A1 regulates its phospholipase-D-dependent redistribution in response to release of Ca2+.
16856845 2006 cAMP phosphodiesterase-4A1 (PDE4A1) has provided the paradigm for the intracellular targeting of phosphodiesterases, a process that underpins compartmentalized cAMP signalling.
16300476 2005 Phosphodiesterase-4 as a potential drug target.
16257373 2005 Keynote review: phosphodiesterase-4 as a therapeutic target.
15738310 2005 Identification and characterization of PDE4A11, a novel, widely expressed long isoform encoded by the human PDE4A cAMP phosphodiesterase gene.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15057824 2004 The DNA sequence and biology of human chromosome 19.
15047569 2004 Differential expression of PDE4 cAMP phosphodiesterase isoforms in inflammatory cells of smokers with COPD, smokers without COPD, and nonsmokers.
14759258 2004 An unappreciated role for RNA surveillance.
12810716 2003 Attenuation of the activity of the cAMP-specific phosphodiesterase PDE4A5 by interaction with the immunophilin XAP2.
12764607 2003 Type 4A cAMP-specific phosphodiesterase is stored in granules of human neutrophils and eosinophils.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11994273 2002 TAPAS-1, a novel microdomain within the unique N-terminal region of the PDE4A1 cAMP-specific phosphodiesterase that allows rapid, Ca2+-triggered membrane association with selectivity for interaction with phosphatidic acid.
11839681 2002 Inhibition of PDE3B augments PDE4 inhibitor-induced apoptosis in a subset of patients with chronic lymphocytic leukemia.
11566027 2001 Purification and characterization of the human PDE4A catalytic domain (PDE4A330-723) expressed in Sf9 cells.
11306681 2001 Molecular cloning, genomic positioning, promoter identification, and characterization of the novel cyclic amp-specific phosphodiesterase PDE4A10.
11156964 2001 HIV-1 Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/AKT/cyclic nucleoside phosphodiesterase pathway.
11114167 2000 Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+ T cell hyperactivation and HIV type 1 replication.
10393044 1999 Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells.
10206997 1999 Association with the SRC family tyrosyl kinase LYN triggers a conformational change in the catalytic region of human cAMP-specific phosphodiesterase HSPDE4A4B. Consequences for rolipram inhibition.
9677330 1998 Identification and characterization of the human homologue of the short PDE4A cAMP-specific phosphodiesterase RD1 (PDE4A1) by analysis of the human HSPDE4A gene locus located at chromosome 19p13.2.
9371714 1997 Molecular cloning and transient expression in COS7 cells of a novel human PDE4B cAMP-specific phosphodiesterase, HSPDE4B3.
8940140 1996 The human cyclic AMP-specific phosphodiesterase PDE-46 (HSPDE4A4B) expressed in transfected COS7 cells occurs as both particulate and cytosolic species that exhibit distinct kinetics of inhibition by the antidepressant rolipram.
8413254 1993 A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs.
8009369 1994 Chromosome localizations of genes for five cAMP-specific phosphodiesterases in man and mouse.
7888306 1994 Molecular cloning and expression, in both COS-1 cells and S. cerevisiae, of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-IVA-h6.1).
7772058 1995 Molecular cloning of a novel splice variant of human type IVA (PDE-IVA) cyclic AMP phosphodiesterase and localization of the gene to the p13.2-q12 region of human chromosome 19 [corrected].
2160582 1990 Cloning and expression of cDNA for a human low-Km, rolipram-sensitive cyclic AMP phosphodiesterase.