Property Summary

NCBI Gene PubMed Count 81
PubMed Score 2168.99
PubTator Score 1655.98

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (4)

Disease Target Count
Neoplasm Metastasis 138

Expression

  Differential Expression (21)

Disease log2 FC p
gastric cancer 1.300 9.4e-03
pancreatic cancer 1.600 2.0e-03
malignant mesothelioma -3.800 4.6e-08
osteosarcoma 2.317 6.1e-08
sonic hedgehog group medulloblastoma 3.600 2.4e-07
type II diabetes mellitus and post-ische... 1.300 3.3e-02
atypical teratoid / rhabdoid tumor 1.900 5.4e-03
medulloblastoma, large-cell 1.400 8.8e-05
non-small cell lung cancer -1.977 6.3e-21
colon cancer -1.800 1.4e-02
lung cancer 1.200 9.1e-04
diabetes mellitus -1.200 9.2e-03
lung adenocarcinoma -1.700 9.8e-18
posterior fossa group A ependymoma 1.500 9.3e-10
pancreatic carcinoma 1.600 2.0e-03
breast carcinoma -1.300 6.7e-25
Breast cancer -3.300 3.3e-17
ulcerative colitis -1.200 2.4e-04
ovarian cancer -2.900 1.4e-14
pituitary cancer 1.900 1.4e-02
head and neck cancer -2.000 3.4e-02

Protein-protein Interaction (4)

Gene RIF (53)

PMID Text
26657792 Our data showed a significant and previously undocumented upregulation of PDE5 in both rat and human BPH.
26299804 cGMP PDE isozymes, PDE5 and 10, are elevated in colon tumor cells compared with normal colonocytes, and inhibitors and siRNAs can selectively suppress colon tumor cell growth
25837309 Overexpression of PDE5 in papillary thyroid carcinomas.
25322361 PDE5A appears to jointly influence amygdala volume and emotion recognition performance.
25247292 Results show that Ser102 and Ser104 may influence the conformational flexibility of PDE5A, which may in turn influence phosphorylation status, allosteric regulation by cGMP or other as yet unknown regulatory mechanisms for PDE5A.
24112792 inhibition of PDE5 can counteract apoptosis during aging by modulating proand antiapoptotic molecules and the APP pathway.
23527037 Myocardial PDE5 expression is increased in the hearts of humans and mice with chronic pressure overload.
23033484 analysis of amino acid residues responsible for the selectivity of tadalafil binding to two closely related phosphodiesterases, PDE5 and PDE6
22960860 it is concluded that assessment of PDE5 and PDE9 expression may be useful in the differential diagnosis of benign and malignant breast disease and successful treatment of breast cancer
22843873 PDE5 is highly expressed and increases ( approximately 130%) during growth whereas ABCC5 exhibited low to moderate expression, with a moderate increase ( approximately 40%) during growth
21987443 Treatment of L-1236 with PDE5A-inhibitor sildenafil or with siRNA directed against PDE5A and concomitant stimulation with cyclic guanosine monophosphate (cGMP) resulted in enhanced apoptosis, indicating PDE5A as an oncogene.
21736695 PDE9 is widely distributed in the urothelial epithelium of the human lower urinary tract and its potential roles may be different from those of PDE5.
21697861 found in smooth muscle wall of blood vessels transversing the clitoral supepithelial and stromal space
21525805 These studies suggest a novel role for PDE5 in erythrocytes.
21505183 PDE5 inhibition by sulindac sulfide selectively induces apoptosis and attenuates oncogenic Wnt/beta-catenin-mediated transcription in human breast tumor cells
21425347 Solved is the crystal structure of the structurally uncharacterized PDE5A GAF-B domain.
21421555 the spatial localization of PDE5A at the level of caveolin-rich lipid rafts allows for a feedback loop between endothelial PDE5A and nitric oxide synthase (NOS3)
21215707 In melanoma cells, oncogenic (V600E) BRAF signaling downregulates PDE5A through the transcription factor BRN2, leading to increased cGMP and Ca2+ and the induction of invasion through increased cell contractility.
21193396 Distinct allostery induced in the cyclic GMP-binding, cyclic GMP-specific phosphodiesterase (PDE5) by cyclic GMP, sildenafil, and metal ions.
20861010 Conformation changes, N-terminal involvement, and cGMP signal relay in the phosphodiesterase-5 GAF domain.
20563733 Suggest that PDE5A is associated with increased disease susceptibility, pathological progression, and development of proteinuria in childhood IgA nephropathy.
20563733 Observational study of gene-disease association. (HuGE Navigator)
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20351714 Observational study of gene-disease association. (HuGE Navigator)
20346360 Observational study of gene-disease association. (HuGE Navigator)
20332439 High PDE5A1 expression is associated with malignant melanoma.
20332099 Observational study of gene-disease association. (HuGE Navigator)
20308615 Myocardial oxidative stress increases PDE5 expression in the failing heart
20196613 Data show that the identified compound will be a useful agent for evaluating the therapeutic potential of central inhibition of PDE5.
20177899 The distribution of PDE-5 and NOD II may indicate a physiologic role in the regulatory function of human vagina.
19996273 Data show that SS increased intracellular cGMP levels and activated protein kinase G, and selectively inhibited PDE5 in breast tumor cells.
19961855 PDE5-inhibition blocks TRPC6 channel activation and associated Cn/NFAT activation signaling by PKG-dependent channel phosphorylation
19852267 The rAd5-shRNA-PDE5A3 can obviously increase the cGMP level in the smooth muscle cells of human corpus cavernosum, and enhance the inhibition of the PDE5 gene.
19139381 Increased myocardial PDE5 expression in patients with advanced cardiomyopathy may contribute to the development of heart failure and represents an important therapeutic target.
18757735 may define a molecular mechanism by which PDE5 inhibition can differentially impact selected cellular functions of platelets, and perhaps of other cell types
18635550 analysis of functional chimeras of the phosphodiesterase 5 and 10 tandem GAF domains
18293931 GAF domains of PDE5A can act as sensors and intracellular sinks for cyclic GMP, but not cyclic AMP.
17906676 The PDE-5A was expressed in both pre-adipocytes and adipocytes. PDE-5A mRNA and protein levels decreased as pre-adipocytes differentiated.
17138653 PDE5 may be a possible therapeutic target in bladder dysfunction for ameliorating irritative lower urinary tract symptoms.
17017938 Virtually all tissues and cell types express PDE5, with heart and cardiomyocytes being contentious; PDE5A1 and PDE5A2 are ubiquitous, but PDE5A3 is specific to smooth muscle, as described in this review.
16690614 Subdomains are structurally and functionally interdependent and act in concert in regulating human PDE5.
16407275 Results suggest that glutamine(817) is a positive determinant for phosphodiesterase 5 affinity for cyclic GMP and several inhibitors.
15817798 Phosphodiesterase Type 5 is the main factor regulating cyclic guanosine monophosphate hydrolysis and downstream signaling in human PASMCs.
15640438 PDE5 gene expression and activity are androgen-dependent in vas deferens.
15240816 Phosphorylation of PDE5 seems to act as memory switch for activation leading to long-term desensitization of the signaling pathway.
15175637 no correlations of a novel polymorphism of the PDE5A promoter gene with the intermediate phenotype essential hypertension/erectile dysfunction
14764637 demonstrated, for the first time, that androgens positively regulate phosphodiesterase 5
14668322 Crystal structures of phosphodiesterases 4 and 5 in complex with inhibitor 3-isobutyl-1-methylxanthine
12955149 three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra)
12650945 GAFa domain of PDE5A adopts a structure similar to the GAFb domain of PDE2A, and provides the sole site for cGMP binding in PDE5A
12604588 CGMP-dependent protein kinase I causes NO-induced PDE5 phosphorylation. However, cGMP can directly activate PDE5 without phosphorylation in platelet cytosol, most likely by binding to GAF domains.
12359732 cGMP-directed regulation of PDE5 phosphorylation and the resulting increase in cGMP binding affinity occur largely within the R domain
11896473 Human PDE5A gene encodes three PDE5 isoforms from two alternate promoters.

AA Sequence

MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKATREMVNAWFAERVHTIPVCKE      1 - 70
GIRGHTESCSCPLQQSPRADNSAPGTPTRKISASEFDRPLRPIVVKDSEGTVSFLSDSEKKEQMPLTPPR     71 - 140
FDHDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLISADRYSLFLVCEDSSNDKFLISRLFDVAEG    141 - 210
STLEEVSNNCIRLEWNKGIVGHVAALGEPLNIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVG    211 - 280
VAQAINKKSGNGGTFTEKDEKDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVI    281 - 350
LKKIAATIISFMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTME    351 - 420
PLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGKVKPFNRNDEQ    421 - 490
FLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETRELQSLAAAVVPSAQTLKITDFS    491 - 560
FSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWILSVKKNYRKNVAYHNWRHAFNTAQCMFAALK    561 - 630
AGKIQNKLTDLEILALLIAALSHDLDHRGVNNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQI    631 - 700
LSGLSIEEYKTTLKIIKQAILATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITK    701 - 770
PWPIQQRIAELVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCF    771 - 840
PLLDGCRKNRQKWQALAEQQEKMLINGESGQAKRN                                       841 - 875
//

Text Mined References (85)

PMID Year Title
26657792 2015 Upregulation of Phosphodiesterase type 5 in the Hyperplastic Prostate.
26299804 2015 Suppression of ?-catenin/TCF transcriptional activity and colon tumor cell growth by dual inhibition of PDE5 and 10.
25837309 2015 PDE5 expression in human thyroid tumors and effects of PDE5 inhibitors on growth and migration of cancer cells.
25799991 2015 Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease.
25322361 2015 Pleiotropic locus for emotion recognition and amygdala volume identified using univariate and bivariate linkage.
25247292 2014 Role of Ser102 and Ser104 as regulators of cGMP hydrolysis by PDE5A.
24112792 2014 Effect of phosphodiesterase-5 inhibition on apoptosis and beta amyloid load in aged mice.
23527037 2013 Increased cardiac myocyte PDE5 levels in human and murine pressure overload hypertrophy contribute to adverse LV remodeling.
23033484 2012 Identification of amino acid residues responsible for the selectivity of tadalafil binding to two closely related phosphodiesterases, PDE5 and PDE6.
22960860 2012 Evaluation of PDE5 and PDE9 expression in benign and malignant breast tumors.
22843873 2012 Increased gene expression of the ABCC5 transporter without distinct changes in the expression of PDE5 in human cervical cancer cells during growth.
21987443 2011 t(4;8)(q27;q24) in Hodgkin lymphoma cells targets phosphodiesterase PDE5A and homeobox gene ZHX2.
21736695 2012 Phosphodiesterase type 9 (PDE9) in the human lower urinary tract: an immunohistochemical study.
21697861 Expression and distribution of key enzymes of the cyclic GMP signaling in the human clitoris: relation to phosphodiesterase type 5 (PDE5).
21525805 2011 Identification of cytosolic phosphodiesterases in the erythrocyte: a possible role for PDE5.
21505183 2011 Inhibition of PDE5 by sulindac sulfide selectively induces apoptosis and attenuates oncogenic Wnt/?-catenin-mediated transcription in human breast tumor cells.
21425347 2011 Crystal structure of the GAF-B domain from human phosphodiesterase 5.
21421555 2011 Phosphodiesterase-5A (PDE5A) is localized to the endothelial caveolae and modulates NOS3 activity.
21215707 2011 Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A.
21193396 2011 Distinct allostery induced in the cyclic GMP-binding, cyclic GMP-specific phosphodiesterase (PDE5) by cyclic GMP, sildenafil, and metal ions.
20861010 2010 Conformation changes, N-terminal involvement, and cGMP signal relay in the phosphodiesterase-5 GAF domain.
20595799 2010 Retraction: Expression of phosphodiesterase type 5A in human spermatozoa and influence of its inhibition on motility and functional sperm parameters.
20590607 2010 Signalling pathways involved in sildenafil-induced relaxation of human bladder dome smooth muscle.
20563733 2010 Phosphodiesterase-5 gene (PDE5A) polymorphisms are associated with progression of childhood IgA nephropathy.
20555034 2010 Attenuated proliferation and trans-differentiation of prostatic stromal cells indicate suitability of phosphodiesterase type 5 inhibitors for prevention and treatment of benign prostatic hyperplasia.
20553468 2010 A new era in the treatment of erectile dysfunction: chronic phosphodiesterase type 5 inhibition.
20491634 2010 PDE5 inhibitors and their applications.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20351714 2011 Poor replication of candidate genes for major depressive disorder using genome-wide association data.
20346360 2010 Genetic risk factors for hepatopulmonary syndrome in patients with advanced liver disease.
20332439 2010 Expression and role of phosphodiesterase 5 in human malignant melanoma cell line.
20332099 2010 A systematic gene-based screen of chr4q22-q32 identifies association of a novel susceptibility gene, DKK2, with the quantitative trait of alcohol dependence symptom counts.
20308615 2010 Oxidative stress regulates left ventricular PDE5 expression in the failing heart.
20196613 2010 Design, synthesis, and biological evaluation of 3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one, a potent, orally active, brain penetrant inhibitor of phosphodiesterase 5 (PDE5).
20177899 2011 PDE-5 and NOS II mRNA expression in menopausal women: a molecular biology study.
19996273 2009 Sulindac sulfide selectively inhibits growth and induces apoptosis of human breast tumor cells by phosphodiesterase 5 inhibition, elevation of cyclic GMP, and activation of protein kinase G.
19961855 2010 Cyclic GMP/PKG-dependent inhibition of TRPC6 channel activity and expression negatively regulates cardiomyocyte NFAT activation Novel mechanism of cardiac stress modulation by PDE5 inhibition.
19852267 2009 [Impact of rAd5-shRNA- PDE5A3 on cGMP in the smooth muscle cells of human corpus cavernosum].
19139381 2009 Ventricular phosphodiesterase-5 expression is increased in patients with advanced heart failure and contributes to adverse ventricular remodeling after myocardial infarction in mice.
18757735 2008 Compartmentation and compartment-specific regulation of PDE5 by protein kinase G allows selective cGMP-mediated regulation of platelet functions.
18635550 2008 Functional chimeras of the phosphodiesterase 5 and 10 tandem GAF domains.
18293931 2008 The GAF domain of the cGMP-binding, cGMP-specific phosphodiesterase (PDE5) is a sensor and a sink for cGMP.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17906676 2007 Phosphodiesterase-5A and neutral endopeptidase activities in human adipocytes do not control atrial natriuretic peptide-mediated lipolysis.
17138653 2007 Characterization and functional role of androgen-dependent PDE5 activity in the bladder.
17017938 2006 Expression, distribution and regulation of phosphodiesterase 5.
16690614 2006 Characterization of the tandem GAF domain of human phosphodiesterase 5 using a cyanobacterial adenylyl cyclase as a reporter enzyme.
16407275 2006 Phosphodiesterase-5 Gln817 is critical for cGMP, vardenafil, or sildenafil affinity: its orientation impacts cGMP but not cAMP affinity.
16381901 2006 The LIFEdb database in 2006.
15938621 2005 Structural determinants for inhibitor specificity and selectivity in PDE2A using the wheat germ in vitro translation system.
15817798 2005 Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells.
15815621 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
15640438 2005 Expression and functional activity of phosphodiesterase type 5 in human and rabbit vas deferens.
15489336 2004 From ORFeome to biology: a functional genomics pipeline.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15240816 2004 In vivo reconstitution of the negative feedback in nitric oxide/cGMP signaling: role of phosphodiesterase type 5 phosphorylation.
15175637 2004 Cardiovascular effects of sildenafil in hypertensive men with erectile dysfunction and different alleles of the type 5 cGMP-specific phosphodiesterase (PDE5).
15093609 2004 The cGMP-binding, cGMP-specific phosphodiesterase (PDE5): intestinal cell expression, regulation and role in fluid secretion.
14764637 2004 Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14687666 2004 Differentiation of human monocytes in vitro with granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor produces distinct changes in cGMP phosphodiesterase expression.
14668322 2004 Crystal structures of phosphodiesterases 4 and 5 in complex with inhibitor 3-isobutyl-1-methylxanthine suggest a conformation determinant of inhibitor selectivity.
12955149 2003 Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules.
12650945 2003 Modeling and mutational analysis of the GAF domain of the cGMP-binding, cGMP-specific phosphodiesterase, PDE5.
12604588 2003 Direct activation of PDE5 by cGMP: long-term effects within NO/cGMP signaling.
12554648 2003 PDE5 is converted to an activated state upon cGMP binding to the GAF A domain.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12359732 2002 Phosphorylation of isolated human phosphodiesterase-5 regulatory domain induces an apparent conformational change and increases cGMP binding affinity.
11723116 2002 Regulation of cGMP-specific phosphodiesterase (PDE5) phosphorylation in smooth muscle cells.
11602184 2001 The gamma subunit of the rod photoreceptor cGMP phosphodiesterase can modulate the proteolysis of two cGMP binding cGMP-specific phosphodiesterases (PDE6 and PDE5) by caspase-3.
11358813 2001 Exisulind, a novel proapoptotic drug, inhibits rat urinary bladder tumorigenesis.
11230166 2001 Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.
11162575 2001 Identification and regulation of human PDE5A gene promoter.
11076863 2000 DNA cloning using in vitro site-specific recombination.
10859452 2000 Gene expression of the phosphodiesterases 3A and 5A in human corpus cavernosum penis.
10679255 2000 Expression of three isoforms of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in human penile cavernosum.
10679249 2000 Identification of three alternative first exons and an intronic promoter of human PDE5A gene.
10411650 1999 Genomic origin and transcriptional regulation of two variants of cGMP-binding cGMP-specific phosphodiesterases.
10393044 1999 Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells.
9716380 1998 Expression, structure and chromosomal localization of the human cGMP-binding cGMP-specific phosphodiesterase PDE5A gene.
9714779 1998 Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase.
9642111 1998 Molecular cloning and expression of human cGMP-binding cGMP-specific phosphodiesterase (PDE5).
9115850 1996 Characterization of the isoenzymes of cyclic nucleotide phosphodiesterase in human platelets and the effects of E4021.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.
8557689 1996 Isolation and characterization of cDNAs corresponding to two human calcium, calmodulin-regulated, 3',5'-cyclic nucleotide phosphodiesterases.