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Information on EC 3.1.4.53 - 3',5'-cyclic-AMP phosphodiesterase
for references in articles please use BRENDA:EC3.1.4.53
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EC Tree 3 Hydrolases
3.1 Acting on ester bonds
3.1.4 Phosphoric-diester hydrolases
3.1.4.53 3',5'-cyclic-AMP phosphodiesterase
IUBMB Comments
Requires Mg2+ or Mn2+ for activity . This enzyme is specific for 3′,5′-cAMP and does not hydrolyse other nucleoside 3′,5′-cyclic phosphates such as cGMP (cf. EC 3.1.4.17, 3,5-cyclic-nucleotide phosphodiesterase and EC 3.1.4.35, 3,5-cyclic-GMP phosphodiesterase). It is involved in modulation of the levels of cAMP, which is a mediator in the processes of cell transformation and proliferation .
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
- 3.1.4.53
- rolipram
- pulmonary
- phosphodiesterases
- roflumilast
- asthma
- airway
- cyclase
- pka
- psoriasis
- agonist
- apremilast
-
inhale
- tnf
-
camp-dependent
-
atopic
- dermatitis
-
corticosteroid
- cgmp
- forskolin
-
bronchodilator
-
adenylyl
-
eosinophil
-
nausea
-
bronchoalveolar
- emesis
-
long-acting
- theophylline
- camp-pde
- salbutamol
-
ointment
- ibmx
- pruritus
- cilostamide
-
moderate-to-severe
- milrinone
-
bronchoconstriction
-
camp-mediated
- zaprinast
- medicine
- salmeterol
-
pcreb
-
beta2ars
-
beta2-adrenoceptors
-
labas
-
camp-elevating
-
beta2-agonists
- pde10a
-
cgmp-specific
- molecular biology
-
akaps
-
tofacitinib
-
ustekinumab
showSynonyms
pde4b, phosphodiesterase 4, phosphodiesterase-4, camp-phosphodiesterase, camp-specific phosphodiesterase, pde4d3, pde4d5, phosphodiesterase type 4, pde7b, pde7a, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
adenosine 3',5'-cyclicmonophosphate-specific PDE
adenylyl cyclase/cAMP phosphodiesterase
cAMP phosphodiesterase
cAMP-PDE
cAMP-phosphodiesterase
cAMP-phosphodiesterase 1C
cAMP-phosphodiesterase 4
cAMP-selective phosphodiesterase
cAMP-specific PDE
cAMP-specific phosphodiesterase
cAMP-specific phosphodiesterase 8A
cAMP-specific phosphodiesterase-4D5
CAPE protein
CpdA
cyclic nucleotide phosphodiesterase
high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A
-
PDE
PDE1C
PDE4
PDE4A
PDE4A1
PDE4B
PDE4B1
PDE4B2
PDE4B3
PDE4B4
PDE4B5
PDE4C
PDE4D
PDE4D3
PDE4D5
PDE5
PDE7
PDE7A
PDE7A1
PDE7B
PDE8
PDE8A
PDE8B
PdeL
phosphodiesterase 4
phosphodiesterase 4B
phosphodiesterase-4
TGGT1_293000
TgPDE2
adenylyl cyclase/cAMP phosphodiesterase
cf. EC 4.6.1.1, the protein encoded by this gene has a class III adenylyl cyclase (AC) in the C-terminal domain and class I phosphodiesterase (PDE) in the N-terminal domain
adenylyl cyclase/cAMP phosphodiesterase
cf. EC 4.6.1.1, the protein encoded by this gene has a class III adenylyl cyclase (AC) in the C-terminal domain and class I phosphodiesterase (PDE) in the N-terminal domain
adenylyl cyclase/cAMP phosphodiesterase
cf. EC 4.6.1.1, the protein encoded by this gene has a class III adenylyl cyclase (AC) in the C-terminal domain and class I phosphodiesterase (PDE) in the N-terminal domain
adenylyl cyclase/cAMP phosphodiesterase
cf. EC 4.6.1.1, the protein encoded by this gene has a class III adenylyl cyclase (AC) in the C-terminal domain and class I phosphodiesterase (PDE) in the N-terminal domain
CAPE protein
cf. EC 4.6.1.1, the protein encoded by this gene has a class III adenylyl cyclase (AC) in the C-terminal domain and class I phosphodiesterase (PDE) in the N-terminal domain
CAPE protein
cf. EC 4.6.1.1, the protein encoded by this gene has a class III adenylyl cyclase (AC) in the C-terminal domain and class I phosphodiesterase (PDE) in the N-terminal domain
CAPE protein
cf. EC 4.6.1.1, the protein encoded by this gene has a class III adenylyl cyclase (AC) in the C-terminal domain and class I phosphodiesterase (PDE) in the N-terminal domain
CAPE protein
cf. EC 4.6.1.1, the protein encoded by this gene has a class III adenylyl cyclase (AC) in the C-terminal domain and class I phosphodiesterase (PDE) in the N-terminal domain
PDE4
-
-
PDE4
key enzyme involved in the regulation of the smooth muscle relaxation associated to cAMP
PDE4
key enzyme involved in the regulation of the smooth muscle relaxation associated to cAMP
PDE4
-
-
PDE4B5
-
PDE4B5, a novel, super-short, brain-specific cAMP phosphodiesterase-4 variant whose isoform-specifying N-terminal region is identical to that of cAMP phosphodiesterase-4D6
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
adenosine 3',5'-cyclic phosphate + H2O = AMP
-
-
-
-
adenosine 3',5'-cyclic phosphate + H2O = AMP
catalytic reaction mechanism, overview
-
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PATHWAY SOURCE
PATHWAYS
KEGG
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SYSTEMATIC NAME
IUBMB Comments
3',5'-cyclic-AMP 5'-nucleotidohydrolase
Requires Mg2+ or Mn2+ for activity [2]. This enzyme is specific for 3',5'-cAMP and does not hydrolyse other nucleoside 3',5'-cyclic phosphates such as cGMP (cf. EC 3.1.4.17, 3,5-cyclic-nucleotide phosphodiesterase and EC 3.1.4.35, 3,5-cyclic-GMP phosphodiesterase). It is involved in modulation of the levels of cAMP, which is a mediator in the processes of cell transformation and proliferation [3].
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CAS REGISTRY NUMBER
COMMENTARY
9036-21-9
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2'-O-(N-methylanthraniloyl)adenosine-3',5'-cyclic monophosphate + H2O
2'-O-(N-methylanthraniloyl)adenosine-5'-monophosphate
Substrates: fluorescent cAMP analogue
Products: -
Products: -
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
Substrates: -
Products: -
Products: -
?
3',5'-cAMP + H2O
5'-AMP
Substrates: DdPDE4 regulates intercellular cAMP during multicellular development
Products: -
Products: -
?
3',5'-cAMP + H2O
5'-AMP
-
Substrates: specific for 3',5'-cAMP, PDE4
Products: -
Products: -
?
3',5'-cAMP + H2O
5'-AMP
-
Substrates: activity with 3',5'-cAMP is much higher than activity with 3',5'-cGMP, PDE7
Products: -
Products: -
?
3',5'-cAMP + H2O
5'-AMP
-
Substrates: specific for 3',5'-cAMP, PDE8
Products: -
Products: -
?
3',5'-cAMP + H2O
5'-AMP
Substrates: PDE4 hydrolyses selectively 3',5'-cAMP with high affinity
Products: -
Products: -
?
3',5'-cAMP + H2O
5'-AMP
Substrates: specific substrate
Products: -
Products: -
?
3',5'-cAMP + H2O
5'-AMP
Substrates: LmjPDEB1 is completely cAMP-specific
Products: -
Products: -
?
3',5'-cAMP + H2O
5'-AMP
Substrates: LmjPDEB2 is completely cAMP-specific
Products: -
Products: -
?
3',5'-cAMP + H2O
5'-AMP
-
Substrates: PDE7A1 possesses a non-catalytic activity that can contribute to the termination of cAMP signals via direct inhibition of C subunit of cAMP-dependent protein kinase
Products: -
Products: -
?
3',5'-cAMP + H2O
5'-AMP
-
Substrates: -
Products: -
Products: -
?
3',5'-cAMP + H2O
5'-AMP
-
Substrates: -
Products: the reaction product, 5'-AMP, is further dephosphorylated to adenosine by PdeA and PdeB
Products: the reaction product, 5'-AMP, is further dephosphorylated to adenosine by PdeA and PdeB
?
3',5'-cAMP + H2O
5'-AMP
Substrates: CpdA possesses 3',5'-cAMP phosphodiesterase activity in vitro
Products: -
Products: -
?
3',5'-cAMP + H2O
5'-AMP
-
Substrates: -
Products: -
Products: -
?
3',5'-cAMP + H2O
adenosine 5'-phosphate
Substrates: -
Products: -
Products: -
?
3',5'-cGMP + H2O
5'-GMP
-
Substrates: activity with 3',5'-cAMP is much higher than activity with 3',5'-cGMP, PDE7
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: DdPDE4 is a unique membrane-bound phosphodiesterase with an extracellular catalytic domain regulating intercellular cAMP during multicellular development
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
-
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
-
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
-
Substrates: the enzyme is specific for cAMP
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
-
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
-
Substrates: determination of reaction rate and mechanism using computational modeling, quantum mechanical/molecular mechanical-free energy perturbation, QM/MM-FE, and QM/MM-Poisson-Boltzmann surface area, PBSA, calculations. The onQM/MMreaction-coordinate calculations including the protein environment of any PDE-catalyzed reaction system identifies a unique catalytic reaction mechanism, overview
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
-
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
-
Substrates: the enzyme is highly specific for cAMP
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
-
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
-
Substrates: the enzyme is specific for cAMP
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: PDE8 is specific for the hydrolysis of cAMP
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: no activity with cGMP
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
-
Substrates: both PDE8A and 8B hydrolyze cAMP with a very high affinity
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
-
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: PDE4B4 isoform may have a distinct functional role in regulating cAMP levels in specific cell types
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
-
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
-
Substrates: attenuation of the activity of the cAMP-specific phosphodiesterase PDE4A5 by interaction with the immunophilin XAP2
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: the enzyme is specific fpr cAMP
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: no activity with cGMP
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
AMP
-
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
AMP
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
AMP
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
AMP
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
AMP
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
AMP
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
AMP
-
Substrates: -
Products: -
Products: -
?
cAMP + H2O
5'-AMP
-
Substrates: degradation of extracellular cAMP
Products: -
Products: -
?
cAMP + H2O
5'-AMP
-
Substrates: isoform PDE7A1 possesses a non-catalytic activity that can contribute to the termination of cAMP signals via direct inhibition of C subunit of cAMP-dependent protein kinase
Products: -
Products: -
?
additional information
?
-
-
Substrates: isoform PDE4 regulates both GalphaS-dependent and GalphaS-indeoendent cAMP pools in the neurons controling locomotion rate
Products: -
Products: -
?
additional information
?
-
-
Substrates: cGMP is hydrolyzed at least 100fold more slowly than cAMP
Products: -
Products: -
?
additional information
?
-
Substrates: cGMP is hydrolyzed at least 100fold more slowly than cAMP
Products: -
Products: -
?
additional information
?
-
-
Substrates: PDE4 may be involved in the cyclic nucleotide-mediated control of smooth muscle tone
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme variants PDE4B and/or PDE4D regulate cell growth through cAMP targets in the HMG malignant melanoma cell
Products: -
Products: -
?
additional information
?
-
-
Substrates: interaction of PDE4D5 with both the N- and C-domains of beta-arrestin 2 are essential for beta2-adrenoceptor regulation
Products: -
Products: -
?
additional information
?
-
Substrates: interaction of PDE4D5 with both the N- and C-domains of beta-arrestin 2 are essential for beta2-adrenoceptor regulation
Products: -
Products: -
?
additional information
?
-
-
Substrates: PDE4D5 plays a nonredundant and functionally significant role in its interaction with beta-arrestin and in the mechanics of beta2-adrenergic receptor signalling
Products: -
Products: -
?
additional information
?
-
Substrates: PDE4D deficiency may contribute to heart failure and arrhythmias by promoting defective regulation of the RyR2 channel in humans
Products: -
Products: -
?
additional information
?
-
Substrates: PDE4D deficiency may contribute to heart failure and arrhythmias by promoting defective regulation of the RyR2 channel in humans
Products: -
Products: -
?
additional information
?
-
Substrates: PDE4D deficiency may contribute to heart failure and arrhythmias by promoting defective regulation of the RyR2 channel in humans
Products: -
Products: -
?
additional information
?
-
-
Substrates: wild-type enzyme shows no activity with cGMP, mutant enzymes D440N and D440A show activity with cGMP
Products: -
Products: -
?
additional information
?
-
Substrates: no hydrolysis of cGMP
Products: -
Products: -
?
additional information
?
-
Substrates: PDE7B does not hydrolyse cGMP
Products: -
Products: -
?
additional information
?
-
-
Substrates: PDE7B does not hydrolyse cGMP
Products: -
Products: -
?
additional information
?
-
-
Substrates: recruitment of PDE4 to the beta2 adrenergic receptor
Products: -
Products: -
?
additional information
?
-
-
Substrates: protein-protein interactions between EPAC1 and PDE4D, peptide mapping for binding site determination. A cell-permeable variant of this peptide antagonizes EPAC1-PDE4D binding and directly alters vascular endothelial cell permeability
Products: -
Products: -
?
additional information
?
-
-
Substrates: PDE4B is involved in LPS signaling
Products: -
Products: -
?
additional information
?
-
-
Substrates: PDE4 is a component of signaling pathways involved in the mediation of antidepressant activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: PDE7A1 possesses a non-catalytic activity that can contribute to the termination of cAMP signals via direct inhibition of the C subunit of the cAMP-dependent kinase
Products: -
Products: -
?
additional information
?
-
Substrates: PDE7B does not hydrolyse cGMP
Products: -
Products: -
?
additional information
?
-
-
Substrates: PDE7B does not hydrolyse cGMP
Products: -
Products: -
?
additional information
?
-
-
Substrates: PDE4 regulates adenosine A2A receptor signaling in striatopallidal neurons
Products: -
Products: -
?
additional information
?
-
-
Substrates: Myxococcus xanthus PdeA and PdeB, enzymes hydrolyze 3',5'- and 2',3'-cyclic AMP to adenosine, and also demonstrate phosphatase activity toward nucleoside 5'-tri-, 5'-di-, 5'- and 3'-monophosphates with highest activities for nucleoside 5'-monophosphates. PdeA and PdeB also show high phosphomonoesterase activities against 50-UMP, 3'-AMP, and 3'-GMP, low activities against 5'-dAMP, and no activities toward 2'-AMP and 2'-GMP
Products: -
Products: -
?
additional information
?
-
Substrates: iron and conserved residues are essential for CpdA activity, the catalytic mechanism for Pseudomonas aeruginosa CpdA utilizes a Fe3+-Fe2+ center
Products: -
Products: -
?
additional information
?
-
-
Substrates: iron and conserved residues are essential for CpdA activity, the catalytic mechanism for Pseudomonas aeruginosa CpdA utilizes a Fe3+-Fe2+ center
Products: -
Products: -
?
additional information
?
-
-
Substrates: during development PDE4 is the major PDE
Products: -
Products: -
?
additional information
?
-
-
Substrates: almost all the PDE4D isoforms, known as the main cAMP-regulated rolipramsensitive PDE in Sertoli cells, are expressed throughout the early postpartum period, whereas only the short PDE4D isoforms (PDE4D1 and PDE4D2) are transcriptionally regulated by FSH
Products: -
Products: -
?
additional information
?
-
-
Substrates: increased PDE4 activity, specifically phosphodiesterase 4B4 activity, reduces beta-adrenergic signaling in the kidney and contributes to salt-sensitive hypertension in the Dahl salt-sensitive rat
Products: -
Products: -
?
additional information
?
-
-
Substrates: TbrPDEB1 and TbrPDEB2 are essential for virulence, making them valuable potential targets for new PDE-inhibitor based trypanocidal drugs
Products: -
Products: -
?
additional information
?
-
Substrates: TbrPDEB1 and TbrPDEB2 are essential for virulence, making them valuable potential targets for new PDE-inhibitor based trypanocidal drugs
Products: -
Products: -
?
additional information
?
-
Substrates: TbrPDEB1 and TbrPDEB2 are essential for virulence, making them valuable potential targets for new PDE-inhibitor based trypanocidal drugs
Products: -
Products: -
?
additional information
?
-
Substrates: TbrPDEB1 and TbrPDEB2 are essential for virulence, making them valuable potential targets for new PDE-inhibitor based trypanocidal drugs
Products: -
Products: -
?
additional information
?
-
Substrates: cGMP neither activates the enzyme nor competes as a substrate
Products: -
Products: -
?
additional information
?
-
-
Substrates: cGMP neither activates the enzyme nor competes as a substrate
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with cGMP
Products: -
Products: -
?
additional information
?
-
Substrates: no activity with cGMP
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with up to 0.1 mM cGMP
Products: -
Products: -
?
additional information
?
-
Substrates: no activity with up to 0.1 mM cGMP
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3',5'-cAMP + H2O
5'-AMP
Substrates: DdPDE4 regulates intercellular cAMP during multicellular development
Products: -
Products: -
?
3',5'-cAMP + H2O
5'-AMP
-
Substrates: PDE7A1 possesses a non-catalytic activity that can contribute to the termination of cAMP signals via direct inhibition of C subunit of cAMP-dependent protein kinase
Products: -
Products: -
?
3',5'-cAMP + H2O
5'-AMP
-
Substrates: -
Products: the reaction product, 5'-AMP, is further dephosphorylated to adenosine by PdeA and PdeB
Products: the reaction product, 5'-AMP, is further dephosphorylated to adenosine by PdeA and PdeB
?
3',5'-cAMP + H2O
5'-AMP
Substrates: CpdA possesses 3',5'-cAMP phosphodiesterase activity in vitro
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: DdPDE4 is a unique membrane-bound phosphodiesterase with an extracellular catalytic domain regulating intercellular cAMP during multicellular development
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
-
Substrates: determination of reaction rate and mechanism using computational modeling, quantum mechanical/molecular mechanical-free energy perturbation, QM/MM-FE, and QM/MM-Poisson-Boltzmann surface area, PBSA, calculations. The onQM/MMreaction-coordinate calculations including the protein environment of any PDE-catalyzed reaction system identifies a unique catalytic reaction mechanism, overview
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
-
Substrates: both PDE8A and 8B hydrolyze cAMP with a very high affinity
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
Substrates: PDE4B4 isoform may have a distinct functional role in regulating cAMP levels in specific cell types
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
AMP
-
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
AMP
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
AMP
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
AMP
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
AMP
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
AMP
Substrates: -
Products: -
Products: -
?
adenosine 3',5'-cyclic phosphate + H2O
AMP
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: isoform PDE4 regulates both GalphaS-dependent and GalphaS-indeoendent cAMP pools in the neurons controling locomotion rate
Products: -
Products: -
?
additional information
?
-
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Substrates: PDE4 may be involved in the cyclic nucleotide-mediated control of smooth muscle tone
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additional information
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Substrates: enzyme variants PDE4B and/or PDE4D regulate cell growth through cAMP targets in the HMG malignant melanoma cell
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additional information
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Substrates: interaction of PDE4D5 with both the N- and C-domains of beta-arrestin 2 are essential for beta2-adrenoceptor regulation
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additional information
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Substrates: interaction of PDE4D5 with both the N- and C-domains of beta-arrestin 2 are essential for beta2-adrenoceptor regulation
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additional information
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Substrates: PDE4D5 plays a nonredundant and functionally significant role in its interaction with beta-arrestin and in the mechanics of beta2-adrenergic receptor signalling
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additional information
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Substrates: PDE4D deficiency may contribute to heart failure and arrhythmias by promoting defective regulation of the RyR2 channel in humans
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additional information
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Substrates: PDE4D deficiency may contribute to heart failure and arrhythmias by promoting defective regulation of the RyR2 channel in humans
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additional information
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Substrates: PDE4D deficiency may contribute to heart failure and arrhythmias by promoting defective regulation of the RyR2 channel in humans
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additional information
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Substrates: recruitment of PDE4 to the beta2 adrenergic receptor
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additional information
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Substrates: protein-protein interactions between EPAC1 and PDE4D, peptide mapping for binding site determination. A cell-permeable variant of this peptide antagonizes EPAC1-PDE4D binding and directly alters vascular endothelial cell permeability
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Substrates: PDE4B is involved in LPS signaling
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Substrates: PDE4 is a component of signaling pathways involved in the mediation of antidepressant activity
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Substrates: PDE7A1 possesses a non-catalytic activity that can contribute to the termination of cAMP signals via direct inhibition of the C subunit of the cAMP-dependent kinase
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Substrates: PDE4 regulates adenosine A2A receptor signaling in striatopallidal neurons
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additional information
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Substrates: Myxococcus xanthus PdeA and PdeB, enzymes hydrolyze 3',5'- and 2',3'-cyclic AMP to adenosine, and also demonstrate phosphatase activity toward nucleoside 5'-tri-, 5'-di-, 5'- and 3'-monophosphates with highest activities for nucleoside 5'-monophosphates. PdeA and PdeB also show high phosphomonoesterase activities against 50-UMP, 3'-AMP, and 3'-GMP, low activities against 5'-dAMP, and no activities toward 2'-AMP and 2'-GMP
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additional information
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Substrates: iron and conserved residues are essential for CpdA activity, the catalytic mechanism for Pseudomonas aeruginosa CpdA utilizes a Fe3+-Fe2+ center
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additional information
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Substrates: iron and conserved residues are essential for CpdA activity, the catalytic mechanism for Pseudomonas aeruginosa CpdA utilizes a Fe3+-Fe2+ center
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Substrates: during development PDE4 is the major PDE
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Substrates: almost all the PDE4D isoforms, known as the main cAMP-regulated rolipramsensitive PDE in Sertoli cells, are expressed throughout the early postpartum period, whereas only the short PDE4D isoforms (PDE4D1 and PDE4D2) are transcriptionally regulated by FSH
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Substrates: increased PDE4 activity, specifically phosphodiesterase 4B4 activity, reduces beta-adrenergic signaling in the kidney and contributes to salt-sensitive hypertension in the Dahl salt-sensitive rat
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additional information
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Substrates: TbrPDEB1 and TbrPDEB2 are essential for virulence, making them valuable potential targets for new PDE-inhibitor based trypanocidal drugs
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additional information
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Substrates: TbrPDEB1 and TbrPDEB2 are essential for virulence, making them valuable potential targets for new PDE-inhibitor based trypanocidal drugs
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additional information
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Substrates: TbrPDEB1 and TbrPDEB2 are essential for virulence, making them valuable potential targets for new PDE-inhibitor based trypanocidal drugs
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additional information
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Substrates: TbrPDEB1 and TbrPDEB2 are essential for virulence, making them valuable potential targets for new PDE-inhibitor based trypanocidal drugs
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
Fe2+
Mg2+
Mn2+
additional information
Co2+
-
the 3',5'-phosphodiesterase enzyme activities of PdeA and PdeB are stimulated 3.2fold and 1.98old, respectively, by 0.05 mM Co2+ at pH 8.0 in 50 mM Tris-HCl buffer
Fe2+
Fe2+ is required for enzyme activity. The catalytic mechanism for CpdA utilizes a Fe3+-Fe2+ center. Addition of 0.01 mM FeCl2, as a source of Fe2+, results in an 2fold stimulation of CpdA activity
Fe2+
iron and conserved residues are essential for CpdA activity
Mg2+
-
the concentration-response curve for Mg2+ is biphasic and ranges from 0.1 to 100 mM. Phosphorylation of PDE-4D3 by protein kinase A produces a monophasic Mg2+ response curve
Mg2+
the enzyme requires the presence of at least 1 mM Mn2+ or Mg2+ for maximal activity in vitro
Mg2+
activity was higher in the presence of Mn2+ than Mg2+ as cofactor
Mn2+
the enzyme requires the presence of at least 1 mM Mn2+ or Mg2+ for maximal activity in vitro
Mn2+
-
the 3',5'-phosphodiesterase enzyme activities of PdeA and PdeB are stimulated 4fold and 2.14old, respectively, by 0.05 mM Mn2+ at pH 8.0 in 50 mM Tris-HCl buffer
Mn2+
activity was higher in the presence of Mn2+ than Mg2+ as cofactor
additional information
-
the 3',5'-phosphodiesterase enzyme activities of PdeA and PdeB are not stimulated by 0.05 mM Ca2+, Mg2+, Fe2+, and Fe3+
additional information
the addition of Mg2+, Mn2+, Zn2+, and Ca2+ has no effect on CdpA
additional information
-
the addition of Mg2+, Mn2+, Zn2+, and Ca2+ has no effect on CdpA
additional information
no effect on enzyme activity by Mg2+, Mn2+, Zn2+, and Ca2+
additional information
-
no effect on enzyme activity by Mg2+, Mn2+, Zn2+, and Ca2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(-)-6-(3-(3-cyclopropyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.1195 mM, PDE7
(2E)-9,10-dimethoxy-3-methyl-2-[(2,4,6-trimethylphenyl)imino]-2,3,6,7-tetrahydro-4H-pyrimido[6,1-a]isoquinolin-4-one
-
(2Z)-9,10-dimethoxy-3-methyl-2-[(2,4,6-trimethylphenyl)imino]-2,3,6,7-tetrahydro-4H-pyrimido[6,1-a]isoquinolin-4-one
-
IC50: 0.00043 mM, PDE4
1-(2,4-dichlorobenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
1-(2-methylbenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
1-(3-chlorobenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
1-(4-chlorobenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
1-(4-methylbenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
10-(4'-N-pyrrolidinobutyl)-2-trifluoromethylphenoxazine
-
increase of Km value in presence of inhibitor
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
-
IC50: 0.0203 mM, PDE7; IC50: 0.0453 mM, PDE4
3-(1-methyl-7-oxo-3-propyl-4,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-N-[2-(1-methylpyrrolidin-2-yl)ethyl]-4-propoxybenzenesulfonamide
-
-
4-(3,4-dimethoxy-phenyl)-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one
-
PDE4 inhibitor, potent inhibitor of isoform PDE4D3
4-(3,4-dimethoxyphenyl)-2-{5-[(2-{5-[2-(2-fluoro-5-methoxyphenyl)ethyl]tetrahydrofuran-2-yl}ethyl)amino]pentyl}-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
the dual PDE4 inhibitor/selective serotonin reuptake inhibitor shows potent and selective serotonin reuptake inhibition
4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid
i.e. NVP; i.e. NVP; i.e. NVP
6-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4,5-dihydropyridazin-3(2H)-one
-
-
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.0513 mM, PDE7; IC50: 0.1008 mM, PDE4
8-methoxymethyl-isobutylmethylxanthine
-
inhibits activated PDE1 and PDE2 isoforms as well as PDE4 and PDE5
alpha-alpha'-dipyridyl
treatment of CpdA with the Fe2+-specific chelator alpha-alpha'-dipyridyl results in a nearly complete loss of activity
apremilast
-
CC-10004, i.e. (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]acetamide, oral phosphodiesterase-4 inhibitor, apremilast shows no marked selectivity among PDE4 isozymes
ayanin
-
i.e. quercetin-3,7,4'-O-trimethylether, non-selective phosphodiesterase 1-4 inhibitor
Biochanin A
-
IC50: 0.0085 mM, more selectively inhibits PDE4 than PDE1 or PDE2
CI-1044
-
i.e. (R)-N-[9-amino-3,4,6,7-tetrahydro-4-oxo-1-phenylpyrrolo[3,2,1-j,k][1,4] benzodiazepin-3-yl]-3-pyridinecarboxamide, selective inhibitor of PDE4, administration of 160 mg/kg of CI-1044 causes perivascular and interstitial inflammation, with infiltrates of admixed neutrophils and macrophages but without evidence of vascular necrosis, PDE4 inhibitor CI-1044 induces changes of vascular tone that could lead to histological alterations in the mesenteric area
cis-(+)-4-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-(-)-4-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-2-[(E)-4-(1H-imidazol-1-yl)but-2-enyl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-2-[2-[2-(1H-imidazol-1-yl)ethoxy]ethyl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-2-[4-(1,4-dioxa-8-azaspiro[4.5]decan-8-ylmethyl)-benzyl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-2-[4-[(1H-imidazol-1-yl)methyl]benzyl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-4-(3,4-dimethoxyphenyl)-2-[2-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-4-(3,4-dimethoxyphenyl)-2-[3-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-4-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4a,5,6,7,8,8a-hexahydrophthalazin-1(2H)-one
-
-
cis-4-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-4-(3,4-dimethoxyphenyl)-2-[4-(piperidin-1-ylmethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-4-(3,4-dimethoxyphenyl)-2-[4-[(4-methylpiperazin-1-yl)methyl]benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-4-(3,4-dimethoxyphenyl)-2-[4-[(4-oxopiperidin-1-yl)-methyl]benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-4-(3,4-dimethoxyphenyl)-2-[4-[(dimethylamino)-methyl]benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-5-(3,4-dimethoxyphenyl)-3-[4-(morpholinomethyl)benzyl]-3,4-diazabicyclo[4.1.0]hept-4-en-2-one
-
-
cis-5-(3,4-dimethoxyphenyl)-3-[4-(morpholinomethyl)benzyl]-3,4-diazabicyclo[4.2.0]oct-4-en-2-one hydrochloride
-
-
DC-TA 46
-
the inhibitor affects memory retention in a visible/hidden-platform water maze task. This memory impairment can be correlated to the decrease of cAMP nucleotide, due to the induction of a PDE4D cAMP-specific PDE isoform
dioclein
-
dioclein is at least 11times more potent in inhibiting calmodulin-activated PDE1 than other PDE types. Among PDE1-PDE5, dioclein is at least 19fold more selective for the activated PDE1 isoform compared to PDE3
erythro-9-[3-(2-hydroxynonyl)]adenine
-
0.1 mM, 12% inhibition, wild-type enzyme
ethyl 2-([4-(3-carbamoylpiperazin-1-yl)-6-[4-(dimethylamino)piperidin-1-yl]pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 2-([4-[(3,4-dimethoxybenzyl)amino]-6-(piperazin-1-yl)pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 2-([4-[4-(dimethylamino)piperidin-1-yl]-6-(4-hydroxypiperidin-1-yl)pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 2-([4-[4-(dimethylamino)piperidin-1-yl]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 2-([4-[4-(dimethylamino)piperidin-1-yl]-6-(morpholin-4-yl)pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 2-([4-[4-(dimethylamino)piperidin-1-yl]-6-[3-(hydroxymethyl)piperidin-1-yl]pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 2-([7-ethyl-6-[(4-sulfamoylbenzyl)amino]-7H-purin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 2-[[4,6-bis(4-hydroxypiperidin-1-yl)pyrimidin-2-yl]amino]-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 2-[[4-[4-[2-(dimethylamino)ethyl]piperazin-1-yl]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl]amino]-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carboxylate
-
IC50: 0.00027 mM, PDE4D; IC50: 0.00031 mM, PDE4B
ethyl 3,5-dimethyl-1-quinolin-8-yl-1H-pyrazole-4-carboxylate
-
IC50: 0.017 mM, PDE4B; IC50: 0.019 mM, PDE4D
ethyl 3,5-dimethyl-1H-pyrazole-4-carboxylate
-
IC50: 0.015 mM, PDE4B; IC50: 0.019 mM, PDE4D
ethyl 3-(4-chlorophenyl)-1-phenyl-1H-pyrazole-4-carboxylate
-
IC50: 0.00088 mM, PDE4D; IC50: 0.0015 mM, PDE4B
ethyl 3-methyl-5-(4-methylphenyl)-1H-pyrazole-4-carboxylate
-
IC50: 0.06 mM, PDE4B; IC50: 0.082 mM, PDE4D
ethyl 4-methyl-2-([4-(4-methylpiperazin-1-yl)-6-[methyl(3,4,5-trimethoxybenzyl)amino]pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
-
-
ethyl 4-methyl-2-([4-(methylamino)-6-[(4-sulfamoylbenzyl)amino]pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
-
-
ethyl 4-methyl-2-([4-(piperazin-1-yl)-6-[(4-sulfamoylbenzyl)amino]pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
-
-
ethyl 4-methyl-2-([4-[(4-sulfamoylbenzyl)amino]pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
-
-
ethyl 4-methyl-2-([4-[methyl(3,4,5-trimethoxybenzyl)amino]-6-(piperazin-1-yl)pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
-
-
ethyl 4-methyl-2-[[4-(piperazin-1-yl)-7-(3,4,5-trimethoxybenzyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-1,3-thiazole-5-carboxylate
-
-
ethyl 5-amino-1-(4a,5,6,7,8,9a-hexahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)-1H-pyrazole-4-carboxylate
-
IC50: 0.025 mM, PDE4B; IC50: 0.05 mM, PDE4D
imperatorin
-
potent PFE4 inhibitor, imperatorin is significantly more active against PDE4B than PDE4A
luteolin-7-glucoside
-
IC50: 0.043 mM, PDB4, dual inhibition of PDE2 and PDE4
N-[(5S)-5-[2-(3-fluorophenyl)acetamido]-6-[4-(6-methylpyridin-2-yl)piperazin-1-yl]-6-oxohexyl]prop-2-enamide
-
N-[2-(5-chloro-2-nitrophenylthio)phenyl]acetamide
10% inhibition at 0.01 mM; 11% inhibition at 0.01 mM; lead compound for Parkinson's disease treatment
N-[3-(1H-imidazol-1-yl)propyl]-2-[cis-4-(3,4-dimethoxyphenyl)-1-oxo-4a,5,8,8a-tetrahydrophthalazin-2(1H)-yl]acetamide
-
-
O-phospho-L-serine
-
PdeA and PdeB show 59% and 73% residual activity, respectively, for 3',5'-cAMP hydrolysis at 5 mM phosphoserine
O-phospho-L-tyrosine
-
PdeA and PdeB show 44% and 52% residual activity, respectively, for 3',5'-cAMP hydrolysis at 5 mM phosphotyrosine
orthovanadate
-
PdeA and PdeB show 26% and 29% residual activity, respectively, for 3',5'-cAMP hydrolysis at 1 mM orthovanadate
RS-25344
-
phosphorylation of PDE-4D3 increases the sensitivity of the enzyme to inhibition by RS-25344 about 100fold
RS-33793
-
phosphorylation of PDE-4D3 increases the sensitivity of the enzyme to inhibition by RS-33793 about 330fold
XAP2
-
noncompetitive inhibition, aryl-hydrocarbon receptor-interacting protein XAP2 inhibits PDE4A5 activity by XAP2 does not require any intermediate proteins. XAP2 inhibits PDE4A5 and not other PDE4 isoforms
-
Zl-n-91
-
selective PDE4 inhibitor, Zl-n-91 at 0.03, 0.3 or 3 mg/kg dose dependently inhibits PDE4 activity
3-isobutyl-1-methylxanthine
-
the inhibitor binds to a subpocket that comprises key residues Ile336, Phe340, Gln369 and Phe372 of PDE54D2. This subpocket may be a common site for binding nonselective inhibitors
3-isobutyl-1-methylxanthine
nonselective inhibitor, the PDE8A1 catalytic domain is insensitive to 3-isobutyl-1-methylxanthine inhibition
dipyridamole
inhibits activity by approximately 40% at high concentrations
EDTA
-
PdeA and PdeB show 39% residual activity, respectively, for 3',5'-cAMP hydrolysis at 0.1 mM EDTA
isobutylmethylxanthine
0.1 mM, 14% inhibition; 0.1 mM, 32% inhibition
rolipram
-
competitive inhibitor of the cytosol enzyme but as a partial competitive inhibitor of the particulate enzyme. Particulate PDE-46 shows a 60fold higher affinity for rolipram than cytosolic PDE-46
rolipram
-
PDE4 inhibition by rolipram can promote regression of malignant brain tumors when administered as an adjunct to established therapies
rolipram
PDE4 is specifically inhibited by rolipram; PDE4 is specifically inhibited by rolipram; PDE4 is specifically inhibited by rolipram; PDE4 is specifically inhibited by rolipram
rolipram
-
isozyme PDE4A is only partially inhibited by 0.02 mM rolipram, whereas PDE4B is completely inhibited at this concentration
rolipram
-
the inhibitor affects memory retention in a visible/hidden-platform water maze task. This memory impairment can be correlated to the decrease of cAMP nucleotide, due to the induction of a PDE4D cAMP-specific PDE isoform
Rolipramm
binds to PDE4 at two sites; binds to PDE4 at two sites; binds to PDE4 at two sites; binds to PDE4 at two sites
-
Rolipramm
binds to PDE4 at two sites; binds to PDE4 at two sites; binds to PDE4 at two sites; binds to PDE4 at two sites
-
Rolipramm
binds to PDE4 at two sites; binds to PDE4 at two sites; binds to PDE4 at two sites; binds to PDE4 at two sites
-
Zn2+
-
more than 90% inhibition at 0.05 mM Zn2+ in the presence of 0.1 mM EDTA, inhibition can be greatly relieved with EDTA at 0.30 mM
Zn2+
-
the 3',5'-phosphodiesterase enzyme activities of PdeA and PdeB are reduced to 24% and 28%, respectively, by 0.05 mM Zn2+ at pH 8.0 in 50 mM Tris-HCl buffer
additional information
-
the major enzyme activity (isoform PDE8) is insensitive towards 3-isobutyl-methylxanthine
-
additional information
-
not inhibited by quercetin-3,7,3',4'-O-tetramethylether
-
additional information
-
IC 50 for sildenafil and tadalafil is above 10000 nM, PDE7; IC50 for sildenafil is above 100000 nM and IC50 for tadalafil and vardenafil is above 10000 nM, PDE8
-
additional information
-
treatment with oxidant t-butylhydroperoxide results in release of significant amounts of interleukin-8, which is prevented by inhibition of enzyme isoforms PDE1 and PDE4
-
additional information
the enzyme is insensitive (up to 100 mM) to a variety of PDE inhibitors including rolipram, zaprinast, vinpocetine, SKF-94120, and IBMX
-
additional information
-
the enzyme is insensitive (up to 100 mM) to a variety of PDE inhibitors including rolipram, zaprinast, vinpocetine, SKF-94120, and IBMX
-
additional information
-
EHNA, milrinone, rolipram, and zaprinast, which are PDE2, PDE3, and PDE4 inhibitors, respectively, do not inhibit the PDE7B activity up to concentrations of 0.100 mM
-
additional information
zaprinast, rolipram, and milrinone do not significantly inhibit PDE7B
-
additional information
-
zaprinast, rolipram, and milrinone do not significantly inhibit PDE7B
-
additional information
-
not affected by Ca2+, Fe2+, Mn2+, HSCH2CH2OH, methanol, and dimethylsulfoxide
-
additional information
-
not inhibited by alpha-bisabolol, caffeic acid, ferulic acid, quinic acid, rutin, chlorogenic acid, herniarin, and umbelliferone
-
additional information
-
the oxidant t-butylhydroperoxide signifcantly increases the cytosolic calcium concentration. Inhibition of both isoforms PDE1 and PDE4 completely prevent the t-butylhydroperoxide stimulated TNF-alpha release
-
additional information
zaprinast, rolipram, and milrinone do not significantly inhibit PDE7B
-
additional information
-
zaprinast, rolipram, and milrinone do not significantly inhibit PDE7B
-
additional information
-
unlike other cAMP-specific PDEs, PDE8s are insensitive to a common nonselective PDE inhibitor, 3-isobutyl-1-methylxanthine (IBMX), but ca be inhibited by a high concentration of dipyridamole
-
additional information
-
he 3',5'-phosphodiesterase activities of PdeA and PdeB are not inhibited by theophylline, 3-isobuthyl-1-methylxanthine, and beta-glycerophosphate
-
additional information
-
removal of the last 35 amino acids of an N-terminal 80-residue highly conserved region (UCR2) results in a 6fold increase in PDE activity, providing evidence that this part of the molecule acts as an intramolecular inhibitor
-
additional information
TcrPDEA1 is resistant to the typical phosphodiesterase inhibitors, such as IBMX, papaverine and theophylline; not inhibitory: 3-isobutyl-1-methylxanthine, papaverine, theophylline
-
additional information
-
TcrPDEA1 is resistant to the typical phosphodiesterase inhibitors, such as IBMX, papaverine and theophylline; not inhibitory: 3-isobutyl-1-methylxanthine, papaverine, theophylline
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
extract of Ginkgo biloba
-
some beneficial effects of extract of Ginkgo biloba might be due to its modulating influences on cellular cyclic AMP levels via activation of membrane-bound PDE
-
haloperidol
-
chronic treatment with 20 mg/kg clozapine increases PDE4B2 and PDE4B4 expression by 102 and 71%, respectively
isoproterenol
-
0.001 mM isoproterenol triggers a sustained, 2fold increase in PDE4 activity
additional information
-
PDE4B1, PDE4B2, PDE4B3, and PDE4B4 are not changed by chronic haloperidol treatment
-
additional information
expression of cpdA is activated by the cAMP-cAMP receptor protein complex via direct binding to the regulatory region
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.6
3',5'-cGMP
wild type PDE8A1 catalytic domain, in 20 mM Tris-HCl, pH 7.5, 4 mM MnCl2, at 24°C
0.0007
3',5'-cAMP
mutant enzyme T748A, in 20 mM Tris-HCl, pH 7.5, 4 mM MnCl2, at 24°C
0.0018
3',5'-cAMP
wild type PDE8A1 catalytic domain, in 20 mM Tris-HCl, pH 7.5, 4 mM MnCl2, at 24°C
0.0033
3',5'-cAMP
-
PdeA, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40°C
0.005
3',5'-cAMP
-
PdeB, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40°C
0.0067
3',5'-cAMP
the addition of FeCl2 does not significantly influence substrate affinity of CdpA increases the rate of the 5'-AMP production, pH and temperature not specified in the publication
0.00013
adenosine 3',5'-cyclic phosphate
-
PDE7B expressed in transfected COS-7 cells
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.6
3',5'-cGMP
wild type PDE8A1 catalytic domain, in 20 mM Tris-HCl, pH 7.5, 4 mM MnCl2, at 24°C
0.00093
3',5'-cAMP
-
PdeB, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40°C
0.00096
3',5'-cAMP
-
PdeA, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40°C
4
3',5'-cAMP
wild type PDE8A1 catalytic domain, in 20 mM Tris-HCl, pH 7.5, 4 mM MnCl2, at 24°C
4.3
3',5'-cAMP
mutant enzyme T748A, in 20 mM Tris-HCl, pH 7.5, 4 mM MnCl2, at 24°C
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.001
10-(3-pyrrolidin-1-ylpropyl)-2-(trifluoromethyl)-10H-phenoxazine
-
pH 7.5, 30°C
0.00097
10-[3'-[(beta-hydroxyethyl)-piperazino]propyl]-2-trifluoromethylphenoxazine
-
-
0.00038
10-[4'-[(beta-hydroxy ethyl)-piperazino]butyl]-2-trifluoro-methylphenoxazine
-
-
0.000002
4-(3,4-dimethoxyphenyl)-2-{5-[(2-{5-[2-(2-fluoro-5-methoxyphenyl)ethyl]tetrahydrofuran-2-yl}ethyl)amino]pentyl}-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
isoform PDE4D3, pH and temperature not specified in the publication
0.000068
apremilast
-
PDE4 purified from U-937 cells, using 0.001 mM cAMP as substrate, pH and temperature not specified in the publication
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.1195
(-)-6-(3-(3-cyclopropyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
Bos taurus
-
IC50: 0.1195 mM, PDE7
0.00043
(2Z)-9,10-dimethoxy-3-methyl-2-[(2,4,6-trimethylphenyl)imino]-2,3,6,7-tetrahydro-4H-pyrimido[6,1-a]isoquinolin-4-one
Homo sapiens
-
IC50: 0.00043 mM, PDE4
0.000085
(4aS,8aR)-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.0001
1-(2,4-dichlorobenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
Cavia porcellus
-
-
0.0009
1-(2-methylbenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
Cavia porcellus
-
-
0.0024
1-(3-chlorobenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
Cavia porcellus
-
-
0.0006
1-(4-chlorobenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
Cavia porcellus
-
-
0.002
1-(4-methylbenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
Cavia porcellus
-
-
0.0031
10-[4'-[(b-hydroxy ethyl)-piperazino]butyl]-2-trifluoro-methylphenoxazine
Bos taurus
-
-
0.0203 - 0.0453
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
0.0513 - 0.1008
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
0.0085
Biochanin A
Cavia porcellus
-
IC50: 0.0085 mM, more selectively inhibits PDE4 than PDE1 or PDE2
0.0000003
cis-(+)-4-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.0000088
cis-(-)-4-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.0000004
cis-2-[(E)-4-(1H-imidazol-1-yl)but-2-enyl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.0000052
cis-2-[2-[2-(1H-imidazol-1-yl)ethoxy]ethyl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.0000013
cis-2-[4-(1,4-dioxa-8-azaspiro[4.5]decan-8-ylmethyl)-benzyl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.0000007
cis-2-[4-[(1H-imidazol-1-yl)methyl]benzyl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.0000013
cis-4-(3,4-dimethoxyphenyl)-2-[2-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.0000014
cis-4-(3,4-dimethoxyphenyl)-2-[3-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.000001
cis-4-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4a,5,6,7,8,8a-hexahydrophthalazin-1(2H)-one
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.0000009
cis-4-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.0000082
cis-4-(3,4-dimethoxyphenyl)-2-[4-(piperidin-1-ylmethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.000002
cis-4-(3,4-dimethoxyphenyl)-2-[4-[(4-methylpiperazin-1-yl)methyl]benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.0000009
cis-4-(3,4-dimethoxyphenyl)-2-[4-[(4-oxopiperidin-1-yl)-methyl]benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.0000097
cis-4-(3,4-dimethoxyphenyl)-2-[4-[(dimethylamino)-methyl]benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.0000459
cis-5-(3,4-dimethoxyphenyl)-3-[4-(morpholinomethyl)benzyl]-3,4-diazabicyclo[4.1.0]hept-4-en-2-one
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.0000164
cis-5-(3,4-dimethoxyphenyl)-3-[4-(morpholinomethyl)benzyl]-3,4-diazabicyclo[4.2.0]oct-4-en-2-one hydrochloride
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.0168
dioclein
Bos taurus
-
isoform PDE4, pH and temperature not specified in the publication
0.000082
ethyl 2-([4-(3-carbamoylpiperazin-1-yl)-6-[4-(dimethylamino)piperidin-1-yl]pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
Homo sapiens
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.000031
ethyl 2-([4-[(3,4-dimethoxybenzyl)amino]-6-(piperazin-1-yl)pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
Homo sapiens
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.000076
ethyl 2-([4-[4-(dimethylamino)piperidin-1-yl]-6-(4-hydroxypiperidin-1-yl)pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
Homo sapiens
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.000083
ethyl 2-([4-[4-(dimethylamino)piperidin-1-yl]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
Homo sapiens
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00013
ethyl 2-([4-[4-(dimethylamino)piperidin-1-yl]-6-(morpholin-4-yl)pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
Homo sapiens
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00012
ethyl 2-([4-[4-(dimethylamino)piperidin-1-yl]-6-[3-(hydroxymethyl)piperidin-1-yl]pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
Homo sapiens
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00001
ethyl 2-([7-ethyl-6-[(4-sulfamoylbenzyl)amino]-7H-purin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
Homo sapiens
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.000063
ethyl 2-[[4,6-bis(4-hydroxypiperidin-1-yl)pyrimidin-2-yl]amino]-4-methyl-1,3-thiazole-5-carboxylate
Homo sapiens
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.000056
ethyl 2-[[4-[4-[2-(dimethylamino)ethyl]piperazin-1-yl]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl]amino]-4-methyl-1,3-thiazole-5-carboxylate
Homo sapiens
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.000039
ethyl 4-methyl-2-([4-(4-methylpiperazin-1-yl)-6-[methyl(3,4,5-trimethoxybenzyl)amino]pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
Homo sapiens
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.0001
ethyl 4-methyl-2-([4-(methylamino)-6-[(4-sulfamoylbenzyl)amino]pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
Homo sapiens
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00001
ethyl 4-methyl-2-([4-(piperazin-1-yl)-6-[(4-sulfamoylbenzyl)amino]pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
Homo sapiens
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00022
ethyl 4-methyl-2-([4-[(4-sulfamoylbenzyl)amino]pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
Homo sapiens
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00001
ethyl 4-methyl-2-([4-[methyl(3,4,5-trimethoxybenzyl)amino]-6-(piperazin-1-yl)pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
Homo sapiens
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.000006
ethyl 4-methyl-2-[[4-(piperazin-1-yl)-7-(3,4,5-trimethoxybenzyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-1,3-thiazole-5-carboxylate
Homo sapiens
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.025 - 0.05
ethyl 5-amino-1-(4a,5,6,7,8,9a-hexahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)-1H-pyrazole-4-carboxylate
0.043
luteolin-7-glucoside
Cavia porcellus
-
IC50: 0.043 mM, PDB4, dual inhibitionof PDE2 and PDE4
0.105
N-[(5S)-5-[2-(3-fluorophenyl)acetamido]-6-[4-(6-methylpyridin-2-yl)piperazin-1-yl]-6-oxohexyl]prop-2-enamide
Trypanosoma cruzi
30°C, pH 7.5
0.0021
N-[2-(5-chloro-2-nitrophenylthio)phenyl]acetamide
Homo sapiens
pH not specified in the publication, 30°C
0.0000143
N-[3-(1H-imidazol-1-yl)propyl]-2-[cis-4-(3,4-dimethoxyphenyl)-1-oxo-4a,5,8,8a-tetrahydrophthalazin-2(1H)-yl]acetamide
Homo sapiens
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30°C
0.01
additional information
Homo sapiens
-
IC 50 for sildenafil and tadalafil is above 10000 nM, PDE7
-
0.0203
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
Bos taurus
-
IC50: 0.0203 mM, PDE7
0.0453
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
Bos taurus
-
IC50: 0.0453 mM, PDE4
0.0658
3-isobutyl-1-methylxanthine
Homo sapiens
mutant enzyme T748A, in 20 mM Tris-HCl, pH 7.5, 4 mM MnCl2, at 24°C
0.698
3-isobutyl-1-methylxanthine
Homo sapiens
wild type enzyme, in 20 mM Tris-HCl, pH 7.5, 4 mM MnCl2, at 24°C
0.00018
4-[(2-chloro-4-nitrophenyl)thio]-pyridine
Homo sapiens
pH not specified in the publication, 30°C
0.0066
4-[(2-chloro-4-nitrophenyl)thio]-pyridine
Homo sapiens
pH not specified in the publication, 30°C
0.0073
4-[(2-chloro-4-nitrophenyl)thio]-pyridine
Homo sapiens
pH not specified in the publication, 30°C
0.00057
4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid
Homo sapiens
pH 7.5, 25°C
0.00065
4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid
Homo sapiens
pH 7.5, 25°C
0.0033
4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid
Homo sapiens
pH 7.5, 25°C
0.0057
4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid
Homo sapiens
pH 7.5, 25°C
0.0513
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
Bos taurus
-
IC50: 0.0513 mM, PDE7
0.1008
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
Bos taurus
-
IC50: 0.1008 mM, PDE4
0.00002
apremilast
Homo sapiens
-
recombinant isoform PDE4A4, using 0.001 mM cAMP as substrate, pH and temperature not specified in the publication
0.00003
apremilast
Homo sapiens
-
recombinant isoform PDE4D3, using 0.001 mM cAMP as substrate, pH and temperature not specified in the publication
0.000049
apremilast
Homo sapiens
-
recombinant isoform PDE4B2, using 0.001 mM cAMP as substrate, pH and temperature not specified in the publication
0.00005
apremilast
Homo sapiens
-
recombinant isoform PDE4C2, using 0.001 mM cAMP as substrate, pH and temperature not specified in the publication
0.000074
apremilast
Homo sapiens
-
PDE4 purified from U-937 cells, using 0.001 mM cAMP as substrate, pH and temperature not specified in the publication
0.00159
carboxyamidotriazole
Mus musculus
-
enzyme from peritoneal macrophage, at pH 8.0 and 30°C
0.00562
carboxyamidotriazole
Mus musculus
-
enzyme from Lewis lung carcinoma cells, at pH 8.0 and 30°C
0.00027
ethyl 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carboxylate
Homo sapiens
-
IC50: 0.00027 mM, PDE4D
0.00031
ethyl 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carboxylate
Homo sapiens
-
IC50: 0.00031 mM, PDE4B
0.017
ethyl 3,5-dimethyl-1-quinolin-8-yl-1H-pyrazole-4-carboxylate
Homo sapiens
-
IC50: 0.017 mM, PDE4B
0.019
ethyl 3,5-dimethyl-1-quinolin-8-yl-1H-pyrazole-4-carboxylate
Homo sapiens
-
IC50: 0.019 mM, PDE4D
0.00088
ethyl 3-(4-chlorophenyl)-1-phenyl-1H-pyrazole-4-carboxylate
Homo sapiens
-
IC50: 0.00088 mM, PDE4D
0.0015
ethyl 3-(4-chlorophenyl)-1-phenyl-1H-pyrazole-4-carboxylate
Homo sapiens
-
IC50: 0.0015 mM, PDE4B
0.06
ethyl 3-methyl-5-(4-methylphenyl)-1H-pyrazole-4-carboxylate
Homo sapiens
-
IC50: 0.06 mM, PDE4B
0.082
ethyl 3-methyl-5-(4-methylphenyl)-1H-pyrazole-4-carboxylate
Homo sapiens
-
IC50: 0.082 mM, PDE4D
0.025
ethyl 5-amino-1-(4a,5,6,7,8,9a-hexahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)-1H-pyrazole-4-carboxylate
Homo sapiens
-
IC50: 0.025 mM, PDE4B
0.05
ethyl 5-amino-1-(4a,5,6,7,8,9a-hexahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)-1H-pyrazole-4-carboxylate
Homo sapiens
-
IC50: 0.05 mM, PDE4D
0.0000002
PF-04957325
Mus musculus
-
PDE8B, pH and temperature not specified in the publication
0.0000007
PF-04957325
Mus musculus
-
PDE8A, pH and temperature not specified in the publication
0.00001
rolipram
Homo sapiens
-
in 20 mM Tris-HCl at pH 7.4, 10 mM MgCl2, and 0.1 mM EDTA, at 30°C
0.0007
rolipram
Bos taurus
-
isoform PDE4, pH and temperature not specified in the publication
0.131
vinpocetine
Bos taurus
-
isoform PDE4, pH and temperature not specified in the publication
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0058
substrate: adenosine 3',5'-cyclic phosphate, pH 8.0, 25°C
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5 - 8.5
-
PdeA and PdeB have slightly alkaline pH optima (pH 7.5-8.5) for 3',5'-cAMP hydrolysis in 0.1 M Tris-HCl buffer
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.3 - 9.2
-
pH 6.3: about 40% of maximal activity, pH 9.2: about 80% of maximal activity
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40
-
the optimum temperatures for the 3',5'-cAMP phosphodiesterase activity of PdeA is 40°C
50
-
the optimum temperatures for the 3',5'-cAMP phosphodiesterase activity of PdeB is 50°C
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
isoform PDE4, enzyme is expressed during single cell stages and expression increases after 9 h of starvation
SwissProt
brenda
-
691859, 692724, 710817, 711379, 711443, 711630, 711812, 713394, 715546, 716016, 716435, 729557, 729990
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isoform PDE4B5, variant of PDE4B with a different 5'-terminus
SwissProt
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patients with idiopathic pulmonary arterial hypertension or secondary pulmonary hypertension
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isoform PDE4D, short variants PDE4D1 and PDE4D2 are transcriptionally regulated by follicle-stimulating hormone
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isoform PDEB1, expression in all developmental stages
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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phosphodiesterase 4 is detected in smooth muscle cells of the wall, and in the cytoplasm of luminal endothelial cells of cavernous arteries
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presence of isoform PDE4 in nonvascular smooth musculature of the corpus carnosum
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highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order
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lowering cyclic adenosine-3',5'-monophosphate levels by expression of a cAMP-specific phosphodiesterase decreases intrinsic pulsatile gonadotropin-releasing hormone secretion from GT1 cells
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Leydig cells express both PDE8A and PDE8B isoforms
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PDE4B. Ablation of PDE4B partially protects mice from LPS-induced shock
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gingiva-derived malignant melanoma cell, expression of variants PDE4B and PDE4D
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monocytic cells may express different PDE4 isozymes, depending on their state of activation or differentiation. These isozymes could thus regulate intracellular cAMP levels at various stages of monocyte activation and could thereby be important in limiting the inflammatory response
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strong expression of isoform PDE4 throughout the nervous system
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abundantly present in the fibromusclular stroma as well as in glandular structures of the transition zone
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additional information
PDE4A expression in GH-secreting adenomas is highly variable and independent from the presence of the gsp oncogene
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PDE4B expression in GH-secreting adenomas is highly variable and independent from the presence of the gsp oncogene
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the level of PDE4C transcripts in gsp+ tumors is significantly higher than that found in gsp- adenomas
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the level of PDE4D transcripts in gsp+ tumors is significantly higher than that found in gsp- adenomas
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tumor tissues from patients with isolated micronodular adrenocortical disease and no mutations in the coding PDE8B sequence or any other related genes (PRKAR1A, PDE11A) show downregulated PDE8B expression compared to normal adrenal cortex. PDE8B is a PDE gene linked to isolated micronodular adrenocortical disease. It is a candidate causative gene for other adrenocortical lesions linked to the cAMP signaling pathway and possibly for tumors in other tissues
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PDE7A1 co-localizes with PKA II in the Golgi centrosome region
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parietal, frontal, temporal cortex, hippocampus, striatum, thalamus, hypothalamus, substantia nigra, nucleus accumbens, cerebellum
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highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order
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in the brain, PDE4D11 expression levels increase in the cerebellum, but decrease in the hippocampus with progressive age
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isoforms PDE4A, PDE4D, PDE7A, PDE8A, PDE8B show an age-related increase or decrease in mRNA expression in at least 1 of the 4 brain regions examined (hippocampus, cortex, striatum, and cerebellum). mRNA expression of isoforms PDE7A, PDE7B does not change with age. Age-related increases in PDE11A4, PDE8A3, PDE8A4/5, and PDE1C1 protein expression are confirmed in hippocampus of old versus young rodents, as are age-related increases in PDE8A3 protein expression in the striatum
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isoforms PDE4A, PDE4D, PDE7A, PDE8A, PDE8B show an age-related increase or decrease in mRNA expression in at least 1 of the 4 brain regions examined (hippocampus, cortex, striatum, and cerebellum). mRNA expression of isoforms PDE7A, PDE7B does not change with age. Age-related increases in PDE11A4, PDE8A3, PDE8A4/5, and PDE1C1 protein expression are confirmed in hippocampus of old versus young rodents, as are age-related increases in PDE8A3 protein expression in the striatum
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PDE4D11 expression levels increase in the cerebellum with progressive age
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PDE4 is observed in the nonvascular smooth musculature of the corpus cavernosum clitoris, sinusoidal endothelial and subendothelial layers, and nerve fibers innervating the tissue
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presence of isoform PDE4 in nonvascular smooth musculature of the corpus carnosum, in sinusoidal endothelial and subendothelial layers, and nerve fiber innervating the tissue
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age-related increases in isoform PDE8A3 protein expression are confirmed in hippocampus of old versus young rodents
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age-related increases in isoform PDE8A3 protein expression are confirmed in hippocampus of old versus young rodents
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sinusoidal endothelial and subendothelialn layer of clitoris, presence of isoform PDE4
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highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order
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PDE4D represents the main PDE4 isoform in the human heart
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highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order
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PDE4D11 expression levels decrease in the hippocampus with progressive age
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age-related increases in isoforms PDE8A3, PDE8A4/5 and PDE1C1 protein expression are confirmed in hippocampus of old versus young rodents
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age-related increases in isoforms PDE8A3, PDE8A4/5 protein expression are confirmed in hippocampus of old versus young rodents. Relative to young rats, the hippocampi of old rats demonstrate strikingly decreased phosphorylation of GluR1, CaMKIIalpha, and CaMKIIbeta, decreased expression of the transmembrane AMPA regulatory proteins gamma2 (a.k.a. stargazin) and gamma8, and increased trimethylation of H3K27. Expression of isoforms of PDE8A4/5, PDE8A3 correlate with these functional endpoints in young but not old rats
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highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order
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the phosphodiesterase 4B4 isoform present in kidney tissue from spontaneously hypertensive rats, hypertensive Dahl salt-sensitive rats, and Dahl salt-resistant rats, phosphodiesterase 4B expression is detected in the renal vasculature, proximal tubules, and distal tubules
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highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order
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highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order
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most highly expressed in pancreas followed by brain, heart, thyroid, skeletal muscle, eye, ovary, submaxillary gland, epididymus, and liver
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immature cell. Almost all PDE4D variants are expressed throughout the early postpartum period with a specific increase in PDE4 activity in both soluble and particulate fraction of 20 day old Sertoli cells
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isolated from 10-, 20-, and 30-days-old rats. Specific increase in PDE4 activity in both the soluble and particulate subcellular fractions of 20-days-old Sertoli cells. Almost all the PDE4D isoforms, known as the main cAMP-regulated rolipramsensitive PDE in Sertoli cells, are expressed throughout the early postpartum period, whereas only the short PDE4D isoforms (PDE4D1 and PDE4D2) are transcriptionally regulated by FSH. The subcellular distribution and expression of PDE4D proteins are unaffected by the developmental status of the Sertoli cells. Only the expression of short PDE4D1 appears to be upregulated by FSH and only in 20-days-old Sertoli cells, which suggests phenotype-dependent differential regulation of Pde4d1 mRNA translation
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highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order
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PDE4 is present in young and adult gland. During development PDE4 is the major PDE
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highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order. In testis PDE8 is expressed in the seminiferous epithelium in a stage-specific manner
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numerous PDE4D gene-derived variants including PDE4D3, PDE4D5, PDE4D7, PDE4D8, and PDE4D9
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additional information
mRNA expression levels of PDEs 4A, 4B, 4C and 4D are significantly higher in rats than in humans. Higher PDE4 expression levels are correlated with a higher enzyme activity level in rat leukocytes
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additional information
mRNA expression levels of PDEs 4A, 4B, 4C and 4D are significantly higher in rats than in humans. Higher PDE4 expression levels are correlated with a higher enzyme activity level in rat leukocytes
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additional information
mRNA expression levels of PDEs 4A, 4B, 4C and 4D are significantly higher in rats than in humans. Higher PDE4 expression levels are correlated with a higher enzyme activity level in rat leukocytes
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additional information
mRNA expression levels of PDEs 4A, 4B, 4C and 4D are significantly higher in rats than in humans. Higher PDE4 expression levels are correlated with a higher enzyme activity level in rat leukocytes
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additional information
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mRNA expression levels of PDEs 4A, 4B, 4C and 4D are significantly higher in rats than in humans. Higher PDE4 expression levels are correlated with a higher enzyme activity level in rat leukocytes
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additional information
PDE IVB is not detected in Placenta, liver, kidney, or pancreas
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additional information
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PDE IVB is not detected in Placenta, liver, kidney, or pancreas
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additional information
determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview
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additional information
determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview
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additional information
determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview
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additional information
determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview
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additional information
determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview
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additional information
determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview
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additional information
determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview
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additional information
determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview
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additional information
mRNA expression levels of PDEs 4A, 4B, 4C and 4D are significantly higher in rats than in humans. Higher PDE4 expression levels are correlated with a higher enzyme activity level in rat leukocytes
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additional information
mRNA expression levels of PDEs 4A, 4B, 4C and 4D are significantly higher in rats than in humans. Higher PDE4 expression levels are correlated with a higher enzyme activity level in rat leukocytes
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additional information
mRNA expression levels of PDEs 4A, 4B, 4C and 4D are significantly higher in rats than in humans. Higher PDE4 expression levels are correlated with a higher enzyme activity level in rat leukocytes
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
PDE8A accumulates nearby the forming acrosome, in the trans-Golgi apparatus of spermatocytes and spermatids and it follows the fate of this organelle in the later stages translocating to the caudal part of the cell
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colocalization of isoform PDE7A1 with protein kinase II in the golgi-centrosome region
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the enzyme is secreted by the plasmodium during migration
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additional information
TbrPDEB2 is distributed between flagellum and cytoplasm
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predominant localization, recombinant protein expressed in COS-7 cell
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when expressed in COS-7 cells, PDE4A8 localizes predominantly in the cytosol, but 20% of the enzyme is associated with membrane fractions
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the enzyme associated with both the soluble and particulate fractions
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with the exception of one isoform PDE4A, PDE4 enzymes are primarily cytosolic enzymes
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PDE4B5 is distributed predominantly and unevenly within the cytosol
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a fully functional GFP-tagged PdeH is cytosolic but associates dynamically with the plasma membrane and vesicular compartments
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TbrPDEB2 is distributed between flagellum and cytoplasm
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PDE8A accumulates nearby the forming acrosome, in the trans-Golgi apparatus of spermatocytes and spermatids and it follows the fate of this organelle in the later stages translocating to the caudal part of the cell
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colocalization of isoform PDE7A1 with protein kinase II in the golgi-centrosome region
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PDE4A splice variant RD1 contains a membrane-association signal which allows the targeted expression of RD1 within the Golgi complex of human follicular thyroid carcinoma cell lines FTC133 and FTC236
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membrane-bound enzyme with an extracellular domain
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DdPDE4 is a unique membrane-bound phosphodiesterase with an extracellular catalytic domain regulating intercellular cAMP during multicellular development
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about 20% of protein is associated with membrane, recombinant protein expressed in COS-7 cell
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when expressed in COS-7 cells, PDE4A8 localizes predominantly in the cytosol, but 20% of the enzyme is associated with membrane fractions
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helix-1 is important for intracellular targeting of PDE4A1 in living cells, facilitating membrane association, targeting to the trans-Golgi stack and conferring Ca2+-stimulated intracellular redistribution in a manner that is dependent on the phospholipase-D-mediated generation of phosphatidic acid
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PDE4D is associated with the envelope of the nucleus isolated from human cardiac cells
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PDE4 (56%) and PDE3 (44%) are the main cyclic phosphodiesterase activities in cardiac nuclei
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small part of enzyme is associated with the plasma membrane
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PDE4 is mostly associated with the enriched fraction of sarcolemma membranes
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PDE4 is mostly associated with the enriched fraction of sarcolemma membranes
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PDE4 is mostly associated with the enriched fraction of sarcolemma membranes
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additional information
the deletion mutant the GFP-PdeL localizes predominantly to the nucleus
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additional information
the deletion mutant the GFP-PdeL localizes predominantly to the nucleus
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additional information
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the soluble PDE4 activities are mainly related to the long PDE4D isoforms and short PDE4D1 is predominantly particulate
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Highest Expressing Human Cell Lines
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
evolution
malfunction
metabolism
physiological function
additional information
drug target
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the PDE4 inhibitor roflumilast, offers a therapeutic approach to protect neurons against redox stress under conditions such as aging, sleep deprivation, and the associated neurochemical and cognitive changes
drug target
critical role for PDE4/PDE4D in controlling function of the cystic fibrosis transmembrane conductance regulator (CFTR) in an in vivo model and in inducing salivation, hinting at a therapeutic potential of PDE4 inhibition for cystic fibrosis and conditions associated with xerostomia
drug target
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PDE4 inhibition is promising for the treatment of acute neuroinflammation following a stroke
drug target
PDE4 inhibitors are effective in decreasing osteoporosis
drug target
allosteric inhibitor of PDE4D would be effective in the loss of fat mass without changing cognitive function
drug target
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PDE4 inhibition is promising for the treatment of acute neuroinflammation following a stroke
drug target
PDE4 inhibitors are effective in decreasing osteoporosis
drug target
allosteric inhibitor of PDE4D would be effective in the loss of fat mass without changing cognitive function
drug target
PDE4 inhibitors are effective in decreasing osteoporosis
drug target
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PDE4 inhibition is promising for the treatment of acute neuroinflammation following a stroke
drug target
allosteric inhibitor of PDE4D would be effective in the loss of fat mass without changing cognitive function
evolution
all plant taxonomic groups reproducing via motile sperm possess CAPE protein (with class III adenylyl cyclase (AC) in the C-terminal domain and class I phosphodiesterase (PDE) in the N-terminal domain), whereas those that do not produce motile sperm do not possess CAPE protein, with one exception in gymnosperm Cupressales. The phylogenic distribution of CAPE almost corresponds to the evolutionary history of motile sperm production
evolution
all plant taxonomic groups reproducing via motile sperm possess CAPE protein (with class III adenylyl cyclase (AC) in the C-terminal domain and class I phosphodiesterase (PDE) in the N-terminal domain), whereas those that do not produce motile sperm do not possess CAPE protein, with one exception in gymnosperm Cupressales. The phylogenic distribution of CAPE almost corresponds to the evolutionary history of motile sperm production
evolution
all plant taxonomic groups reproducing via motile sperm possess CAPE protein (with class III adenylyl cyclase (AC) in the C-terminal domain and class I phosphodiesterase (PDE) in the N-terminal domain), whereas those that do not produce motile sperm do not possess CAPE protein, with one exception in gymnosperm Cupressales. The phylogenic distribution of CAPE almost corresponds to the evolutionary history of motile sperm production
malfunction
deletion of cpdA results in the accumulation of intracellular cAMP and altered regulation of Pseudomonas aeruginosa virulence traits
malfunction
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PDE4 inhibition together with transforming growth factor-beta1 results in augmented PGE2 production together with increased expression of COX mRNA and protein. inhibitors may attenuate fibroblast activities that can lead to fibrosis, PDE4 inhibitors may be particularly effective in the presence of transforming growth factor-beta1-induced fibroblast stimulation
malfunction
deletion of cpdA results in the accumulation of intracellular cAMP and altered regulation of Pseudomonas aeruginosa virulence traits. The cpdA mutant has a cAMP-independent small-colony, slow-growth phenotype
malfunction
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effects of acute hypoxia on cAMP accumulation induced by PDE inhibitors in oxygen-specific chemosensors, the carotid bodies and in non-chemosensitive CB-related structures: carotid arteries and superior cervical ganglia, overview. Acute hypoxia enhances the effects of IBMX and PDE4 inhibitors on cAMP accumulation in carotid arteries and bodies, while in superior cervical ganglia In SCG, acute hypoxia reduces cAMP accumulation induced by all the four PDE inhibitors
malfunction
loss of PdeH leads to increased accumulation of intracellular cAMP during vegetative and infectious growth. Furthermore, the pdeHD shows 2-3fold enhanced conidiation, precocious appressorial development, loss of surface dependency during pathogenesis, and highly reduced in planta growth and host colonization. A pdeHDELTA/pdeLDELTA mutant shows reduced conidiation, exhibits dramatically increased cAMP levels relative to the wild-type, and is completely defective in virulence
malfunction
a pdeHDELTA/pdeLDELTA mutant shows reduced conidiation, exhibits dramatically increased cAMP levels relative to the wild-type, and is completely defective in virulence
malfunction
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PDE8B KO mice have elevated levels of urinary corticosterone in both basal and stressed conditions compared with their littermate wild-type controls. PDE8B KO mice exhibit adrenal hypersensitivity toward adrenocorticotropin. PDE8B gene ablation increases mRNA expressions of StAR protein and MC2R
malfunction
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in cultured smooth muscle cells, isoform PDE1C deficiency or PDE1 inhibition attenuates smooth muscle cell proliferation and migration
malfunction
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in cultured smooth muscle cells, isoform PDE1C deficiency or PDE1 inhibition attenuates smooth muscle cell proliferation and migration
malfunction
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in cultured smooth muscle cells, isoform PDE1C deficiency or PDE1 inhibition attenuates smooth muscle cell proliferation and migration
malfunction
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DELTAPdel shows defects in conidiation, producing approximately 65% reduced conidiation and forming lowly pigmented aberrant structures. In response to osmotic stress, 1AaPdel was more sensitive to non-ionic osmotic stress than ionic osmotic stress. AaPdel deletion mutants have defects in vegetative growth and hyphal growth
malfunction
mutations in PDE4D in humans predispose to acrodysostosis, associated with cognitive and behavioral deficits
malfunction
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PAN-selective inhibition of cAMP-phosphodiesterase 4 induces gastroparesis in mice
malfunction
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PDE4 inhibition induces hypothermia via effects on behavioral and central autonomous thermoregulation. It affects central body temperature regulation and acts by lowering the cold-defense balance point of behavioral (including posture and locomotion) and autonomous (including cutaneous tail vasodilation) cold-defense mechanisms. Increased D2/3-type dopaminergic signaling, triggers by PDE4 inhibitor-induced and cAMP-mediated dopamine release in the thermoregulatory centers of the hypothalamus, is a significant contributor to PDE4 inhibitor-induced hypothermia
malfunction
in human decreases in PDE4D activity, which represents the main PDE4 isoform in cardiac tissue, might favor idiopathic dilated cardiomyopathy and its deficiency in the ryanodine receptor complex promotes heart failure and arrhythmias
malfunction
in mice PDE4D deficiencies in the ryanodine receptor complex in mice promote heart failure and arrhythmias
metabolism
cyclic AMP-dependent pathways mediate the communication between external stimuli and the intracellular signaling machinery, thereby influencing important aspects of cellular growth, morphogenesis and differentiation. Crucial to proper function and robustness of these signaling cascades is the strict regulation and maintenance of intracellular levels of cAMP through a fine balance between biosynthesis, by adenylate cyclases, and hydrolysis, by cAMP phosphodiesterases
metabolism
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PKA, EPAC1, and PDE4D differentially regulate humanarterial endothelial cell vascular endothelial cadherin-based structures, overview. Protein-protein interactions between EPAC1 and PDE4D serve to foster their integration into vascular endothelial cadherin-based complexes and allow robust local regulation of EPAC1-based stabilization of vascular endothelial cadherin-based adhesions
metabolism
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a transmembrane-adenylyl-cyclase-cAMP-protein kinase A cascade modulated by isoform PDE1C is critical in regulating platelet-derived growth factor -receptor-beta degradation
metabolism
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a transmembrane-adenylyl-cyclase-cAMP-protein kinase A cascade modulated by isoform PDE1C is critical in regulating platelet-derived growth factor -receptor-beta degradation
metabolism
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a transmembrane-adenylyl-cyclase-cAMP-protein kinase A cascade modulated by isoform PDE1C is critical in regulating platelet-derived growth factor -receptor-beta degradation
metabolism
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the concentration of intracellular cAMP is regulated by adenylate cyclase biosynthesis and cAMP phosphodiesterase hydrolysis, which mediate signal transduction and termination
physiological function
CpdA is required for cAMP homeostasis and virulence factor regulation, CpdA affects vfr expression and Vfr protein levels and production of virulence factors ExoS, ToxA, and protease IV
physiological function
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phosphodiesterase 4 contributes to maintenance of retinal vascular tone
physiological function
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in cardiac myocytes coupling of PDE4 members to the beta2 adrenergic receptor regulates several aspects of beta2 adrenergic signaling. Inhibition of PDE4 increases cAMP in response to activation of beta2 adrenergic receptors, but has no effect on beta1 adrenergic signaling, demonstrating the selectivity of PDE association. Recruitment of PDE4 to the beta2 adrenergic receptor allows PDE4 to act locally and hydrolyze cAMP produced in response to activation of this receptor, modulating its downstream effects. PDE4 activation is regulated via phosphorylation by PKA in the UCR or phosphorylation by ERK in the C-terminus, depending on the individual isoform. The regulated release of ATP from erythrocytes occurs via a defined signaling pathway and requires increases in cAMP. It is well recognized that cAMP is a critical second messenger in diverse signaling pathways. In all cells increases in cAMP are localized and regulated by the activity of phosphodiesterases, PDEs. The subcellular localization of PDEs is recognized to be a key mechanism for compartmentalization of cyclic nucleotide signaling. PDEs within these cells regulate the compartmentalization of cAMP signaling allowing for specific cell responses. The subcellular location of PDEs is critical for coupling these enzymes to specific signal transduction pathways, which permit specific PDEs to regulate local increases in cAMP produced by activation of ligand specific receptor
physiological function
CpdA possesses 3',5'-cAMP phosphodiesterase activity in vitro and that it utilizes an iron-dependent catalytic mechanism. The cAMP-dependent transcription factor Vfr directly regulates cpdA expression in response to intracellular cAMP accumulation, thus providing a feedback mechanism for controlling cAMP levels and fine-tuning virulence factor expression. CpdA affects vfr expression and Vfr protein levels. CpdA affects production of virulence factors ExoS, ToxA, and protease IV
physiological function
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the PDE4-catalyzed hydrolysis of cAMP consists of two reaction stages: cAMP hydrolysis and bridging hydroxide ion regeneration. The stage 1 includes the binding of cAMP in the active site, nucleophilic attack of the bridging hydroxide ion on the phosphorus atom of cAMP, cleavage of O3'-P phosphoesteric bond of cAMP, protonation of the departing O3' atom, and dissociation of hydrolysis product, AMP. The stage 2 includes the binding of solvent water molecules with the metal ions in the active site and regeneration of the bridging hydroxide ion. The dissociation of the hydrolysis product is found to be rate-determining for the enzymatic reaction process
physiological function
PDEH is necessary for proper aerial hyphal growth. PdeH-dependent biphasic regulation of cAMP levels during early and late stages of appressorial development. PdeH-mediated sustainance and dynamic regulation of cAMP signaling during Magnaporthe oryzae development is crucial for successful establishment and spread of the blast disease in rice. The PdeH activity is a key regulator of asexual and pathogenic development in Magnaporthe oryzae
physiological function
cAMP-specific PDE 4 isoforms underpin compartmentalized cAMP signalling in mammalian cells through targeting to specific signalling complexes. Phosphorylation of PDE4A5 by MK2 confers the amplification of intracellular cAMP accumulation in response to adenylate cyclase activation by attenuating a major desensitization system to cAMP. Long PDE4 isoforms thus provide a novel node for cross-talk between the cAMP and p38 MAPK signalling systems at the level of MK2
physiological function
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importance of PDE8s in cAMP regulation of steroid production. PDE8A plays an important role in regulating a pool of cAMP that promotes testicular steroidogenesis. PDE8B regulates adrenocorticotropin-stimulated AZF steroidogenesis by both short- and long-term mechanisms
physiological function
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the autocrine production of cAMP and extracellular cAMP-specific phosphodiesterase is an important constituent of the mechanism controlling the motile behavior of the plasmodium
physiological function
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PDE4D regulates both the activity and subcellular localization of EPAC1, mechanism for regulated EPAC1 signaling in these cells, overview
physiological function
mutation in cAMP-specific phosphodiesterase RegA in cells lacking either G protein Galpha2 or Galpha4 subunits has no major effects on developmental morphology but enriches the distribution of the Galpha mutant cells to the prespore/prestalk border in chimeric aggregates. The loss of RegA function has no effect on Galpha4-mediated folate chemotaxis. The RegA gene disruption in cells lacking Galpha4 results in a substantial rescue and acceleration of spore production. This rescue in sporulation requires cell autonomous signaling. Intercellular signals from strains lacking RegA increase the expression of the prestalk gene ecmB and accelerate the vacuolization of stalk cells. Intercellular signaling from the strain lacking both Galpha4 and RegA do not induce ecmA gene expression indicating cell-type specificity in the promotion of prestalk cell development. RegA gene disruption in a Galpha4 overexpression strain does not result in precocious sporulation or stalk cell development
physiological function
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constitutive signaling of the overexpressed HA-tagged 5-hydroxytryptamine4(b) receptor in HEK293 cells is regulated predominantly by cAMP-specific phosphodiesterase PDE4,with a secondary role for dual specific phosphodiesterase PDE3 that is unmasked in the presence of PDE4 inhibition. Overexpressed PDE4D3 and PDE3A1, and to a smaller extent PDE4D5 co-immunoprecipitate constitutively with the 5-hydroxytryptamine4(b) receptor. Phosphodiesterase activity measurements in immunoprecipitates of the 5-hydroxytryptamine4(b) receptor confirm the association of PDE4D3 with the receptor and provide evidence that the activity of this phophodiesterase may be increased upon receptor stimulation with 5-hydroxytryptamine
physiological function
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phosphodiesterase 4B mediates Streptococcus pneumoniae-induced mucin gene MUC5AC up-regulation by inhibiting the expression of a negative regulator MKP-1, which in turn leads to enhanced MAPK ERK activation and subsequent up-regulation of MUC5AC. PDE4B inhibits MKP-1 expression in a cAMP-PKA-dependent manner. PDE4-specific inhibitor rolipram inhibits Streptomyces pneumoniae-induced MUC5AC up-regulation both in vitro and in vivo. PDE4B plays a critical role in MUC5AC induction. Topical and post-infection administration of rolipram into the middle ear potently inhibits Streptomyces pneumoniae-induced MUC5AC up-regulation
physiological function
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isoform PDE4B is involved in beta-adrenergic signaling in the heart. Genetic ablation of PDE4B disrupts beta-adrenergic signaling-induced cAMP transients at the sarcolemma but not in the bulk cytosol of cardiomyocytes. PDE4B regulates beta1-adrenergic signaling-, but not beta2-adrenergic signaling- or PGE2-induced responses. PDE4B shows selective effects on protein kinase A-mediated phosphorylation patterns. PDE4B limits the proein kinase A-mediated phosphorylation of key players in excitation-contraction coupling that reside in the sarcolemmal compartment, including L-type Ca2+ channels and ryanodine receptors, but not phosphorylation of distal cytosolic proteins. beta1-Adrenergic signaling- but not beta2-adrenergic signaling-ligation induced protein kinase A-dependent activation of PDE4B and interruption of this negative feedback with protein kinase A inhibitors increase sarcolemmal cAMP
physiological function
isoform PDE4D7 is important in prostate cancer progression and ischemic stroke
physiological function
the enzyme exhibits protection against oxidative damage and participates in the regulation of the carbon metanolism
physiological function
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hepatic isoforms PDE4A, B and D play a causal role in the development of liver injury and fibrosis
physiological function
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cAMP-phosphodiesterase 1C plays a role in regulating growth factor receptor stability, vascular smooth muscle cell growth, migration, and neointimal hyperplasia
physiological function
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cAMP-phosphodiesterase 1C plays a role in regulating growth factor receptor stability, vascular smooth muscle cell growth, migration, and neointimal hyperplasia
physiological function
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cAMP-phosphodiesterase 1C plays a role in regulating growth factor receptor stability, vascular smooth muscle cell growth, migration, and neointimal hyperplasia
physiological function
a specific pool of cAMP is regulated by PDE8A during spermiogenesis pointing out a possible role of this PDE8 isoform in key events governing the differentiation and maturation of human sperm
physiological function
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the enzyme (Pdel) is a key regulator in conidiation and pathogenesis in Alternaria alternata. It is involved in laccase activity regulation
physiological function
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the enzyme is essential for sclerotia formation, regulation of oxalic acid accumulation, infection cushion functionality and virulence
physiological function
the intracellular concentration of cAMP is regulated through its synthesis by cyclases and its degradation by cyclic nucleotide phosphodiesterases (PDEs)
physiological function
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the enzyme (PDE4) depletes cyclic 3'-5' adenosine monophosphate (cAMP) and, in turn, cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF), the key players in cognitive function
physiological function
PDE4 contributes the majority of total cAMP-hydrolytic capacity in submandibular-, sublingual-, and parotid glands. The enzyme (PDE4) acts within salivary glands to gate saliva secretion that is contingent upon the cAMP/PKA-dependent activation of the cystic fibrosis transmembrane conductance regulator (CFTR)
physiological function
the enzyme (PDE4) participates in the control of cardiovascular function at the level of vessels and heart. PDE4 plays a role in the regulation of endothelial permeability
physiological function
PDE4B, by limiting the amount of Ca2+ entering the cell through the L-type Ca2+ channels, prevents Ca2+ overload and arrhythmias
physiological function
PDE8B can be involved in Leydig cell transformation
physiological function
the enzyme is a central regulator of tachyzoite cyclic nucleotide levels
physiological function
the enzyme (PDE4) participates in the control of cardiovascular function at the level of vessels and heart. PDE4 plays a role in the regulation of endothelial permeability
physiological function
PDE4B, by limiting the amount of Ca2+ entering the cell through the L-type Ca2+ channels, prevents Ca2+ overload and arrhythmias
physiological function
PDE1C might play a causative role in the pathological cardiac remodeling and dysfunction
physiological function
the enzyme (PDE4) participates in the control of cardiovascular function at the level of vessels and heart. PDE4 plays a role in the regulation of endothelial permeability
physiological function
PDE4B, by limiting the amount of Ca2+ entering the cell through the L-type Ca2+ channels, prevents Ca2+ overload and arrhythmias
physiological function
PDE11A homophily dictates mutual social preference due to its ability to regulate membrane-associated pools of cAMP specifically within the CA1 subfield of hippocampus. Mice with 2 intact alleles of Pde11a prefer to interact with Pde11 wild-type mice of the same genetic background over mice or novel objects. Pde11 knockout mice prefer to interact with Pde11 knockout mice over wild-type mice or novel objects
physiological function
-
the enzyme is a central regulator of tachyzoite cyclic nucleotide levels
-
additional information
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PDE4 is a cAMP-specific PDE which has four subfamilies, A thru D, that include over 50 isoforms
additional information
TgPDE2 is activated following Toxoplasma replication to turn off cAMP signaling
additional information
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TgPDE2 is activated following Toxoplasma replication to turn off cAMP signaling
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Show AA Sequence and Transmembrane Helices (4141 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
29000
31000
38800
-
x * 39000, SDS-PAGE, x * 38800, deduced from gene sequence, both N-terminally truncated enzyme
39000
-
x * 39000, SDS-PAGE, x * 38800, deduced from gene sequence, both N-terminally truncated enzyme
58000
87000
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PDE4B1 or PDE4B3 recombinant protein, SDS-PAGE, the 87000 Da band is termed PDE4B1/B3 due to difficulty of resolving it into separate bands using SDS-PAGE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
?
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x * 75000, isoform PDE10 appears on SDS-PAGE as bands of 75000 and 60000 Da in size
?
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x * 60000, isoform PDE10 appears on SDS-PAGE as bands of 75000 and 60000 Da in size
?
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x * 39000, SDS-PAGE, x * 38800, deduced from gene sequence, both N-terminally truncated enzyme
additional information
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signalling scaffold protein RACK, i.e. receptors for activated C-kinase, and beta-arrestin interact with enzyme in mutually exclusive manner at overlapping sites within the N-terminal region of PDE4D5 and at distinct sites within the catalytic domain. Alterations within the level of RACK1 expression may act to modulate signal transduction mediated by beta2-adrenergic receptor through increase in PDE4D5 recruited to the receptor
additional information
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isoform PDE4D interacts with beta-arrestin. Identification of a binding site in the beta-arrestin 2 N-domain for the common PDE4D catalytic unit and two regions in the beta-arrestin 2 C domain that confer specificity for PDE4D5 binding. Reduced interaction of PDE4D5 with beta-arrestin mutants R26A, K18A, or T20A. R286, D291, and L215-H220 of beta-arrestin are important for binding PDE4D5, but not for PDE4D3. Interactions of PDE4D5 with both the N- and C-terminal domains of beta-arrestin are essential for beta2-adrenoceptor regulation
additional information
isoform PDE4D interacts with beta-arrestin. Identification of a binding site in the beta-arrestin 2 N-domain for the common PDE4D catalytic unit and two regions in the beta-arrestin 2 C domain that confer specificity for PDE4D5 binding. Reduced interaction of PDE4D5 with beta-arrestin mutants R26A, K18A, or T20A. R286, D291, and L215-H220 of beta-arrestin are important for binding PDE4D5, but not for PDE4D3. Interactions of PDE4D5 with both the N- and C-terminal domains of beta-arrestin are essential for beta2-adrenoceptor regulation
additional information
isoform PDE4B5 is able to bind the scaffold protein DISC1
additional information
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isoform PDE4B5 is able to bind the scaffold protein DISC1
additional information
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isoform PDE7A1 associates with the dissociated C subunit of cAMP dependent protein kinase, but does not bind tetrameric protein kinase holoenzyme. Binding of protein kinase C subunit inhibits kinase activity in vitro, the N-terminal repeat region f PDE7A1 is sufficient for inhibition
additional information
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enzyme contains two GAF domains and a catalytic domain highly homologous with that of the Trypanosoma brucei family
additional information
enzyme contains two GAF domains and a catalytic domain highly homologous with that of the Trypanosoma brucei family
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
proteolytic modification
protein sequence predicts a leader sequence, two transmembrane segments, and an extracellular catalytic domain
phosphoprotein
phosphorylation of enzyme by cAMP-dependent protein kinase at S123
phosphoprotein
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phosphorylation of PDE-4D3 by protein kinase A produces a monophasic Mg2+ response curve. Phosphorylation of PDE-4D3 increased the sensitivity of the enzyme to inhibition by RS-25344 (about 100fold) and RS-33793 (about 330fold). Phosphorylation of PDE-4D3 induces an apparent conformation change that increases maximum velocity and sensitivity to inhibition by some analogues of nitraquazone
phosphoprotein
-
PDE4 activation is regulated via phosphorylation by PKA in the UCR or phosphorylation by ERK in the C-terminus, depending on the individual isoform
phosphoprotein
the enzyme is phosphorylated and activated by protein kinase A within upstream conserved region 1 and inhibited by phosphorylation at serine 42 within the N-terminal region
phosphoprotein
-
aryl-hydrocarbon receptor-interacting protein XAP2 attenuates the ability of cAMP-dependent protein kinase to phosphorylate PDE4A5
phosphoprotein
treatment of COS7 cells with forskolin, to elevate cAMP levels, produced activation of PDE4B4, which is associated with the phosphorylation of PDE4B4 on Ser-56 within UCR1
phosphoprotein
-
protein kinase A catalyzes phosphorylation (at Ser-54) and activation of isoform PDE4D3. Protein phosphatase 2A associated with muscle A kinase-anchoring protein complexes promotes PDE4D3 dephosphorylation at Ser-54
phosphoprotein
phosphorylation of cAMP-specific PDE4A5 by MAPK-activated protein kinase 2, also called MAPKAPK2. PDE4A5 is phosphorylated at Ser147, within the regulatory UCR1, ultraconserved region 1, domain conserved among PDE4 long isoforms. Phosphorylation by MK2, although not altering PDE4A5 activity, markedly attenuates PDE4A5 activation through phosphorylation by protein kinase A. Phosphorylation by MK2 also triggers a conformational change in PDE4A5 that attenuates PDE4A5 interaction with proteins whose binding involves UCR2, such as DISC1 and AIP, but not the UCR2-independent interacting scaffold protein beta-arrestin
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
catalytic domain of inactive mutant D201N in complex with substrate cAMP at 1.56 A resolution. Q369 forms only one hydrogen bond ith the adenine of cAMP. Structural comparison between isoform PDE4D2-cAMP and PDE10A2-cAMP shows an anti configuration of cAMP in PDE4, but syn in PDE10
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hanging drop method, PDE4D2 in complex with the nonselective inhibitor 3-isobutyl-1-methylxanthine
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hanging-drop vapor-diffusion method, crystal structures of the catalytic domain of phosphodiesterase 4B complexed with AMP (2.0 A), 8-Br-AMP (2.13 A), and rolipram (2.0 A)
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in complex with inhibitor 4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid, comparison with isoforms PDE4A, PDE4B, PDE4C. Inhibitor binds in the same conformation to the deep cAMP substrate pocket and interacts with the same residues in each instance. Detailed structural comparison
in complex with inhibitor 4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid, comparison with isoforms PDE4A, PDE4C, PDE4D. Inhibitor binds in the same conformation to the deep cAMP substrate pocket and interacts with the same resiudues in each instance. Detailed structural comparison
in complex with inhibitor 4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid, comparison with isoforms PDE4B, PDE4C, PDE4D. Inhibitor binds in the same conformation to the deep cAMP substrate pocket and interacts with the same residues in each instance. Detailed structural comparison
molecular dynamics simulations. The second bridging ligand in the active site is HO- rather than H2O, serving as a nucleophile to initialize the catalytic hydrolysis of cAMP
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NMR and CD analysis of the N-terminal 38mer peptide of isoform PDE4D5 which contains the entire signaling scaffold protein RACK1 interaction domain together with a portion of the beta-arrestin binding site. The peptiode has a distinct amphipathic helical structure. Study on binding to RACK1 and to beta-arrestin
unliganded PDE8A1 and in complex with 3-isobuytl-1-methylxanthine, hanging drop vapour diffusion method, using 100 mM sodium cacodylate (pH 6.5), 15% 2-propanol, 30% ethylene glycol, and 8-10% PEG3350 at 4°C
unliganded, detailed structural comparison with isoforms PDE4A, PDE4B, PDE4C
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D448N
-
mutation in conserved active site residue, loss of enzyme function does not affect steady-state acetylcholine release or reception
A590C
-
mutation has no significant influence on substrate affinity or specificity
F484Y
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mutation has no significant influence on substrate affinity or specificity
H305P
the mutation is associated with micronodular adrenocortical disease
L391A
-
mutation has no significant influence on substrate affinity or specificity
P595I
-
mutation leads to 7fold decrease of substrate affinity and an 14fold decrease of the affinity towards the PDE4-specific inhibitor rolipram
S42A
the mutant with 170% activity compared to the wild type enzyme is not phosphorylated at serine 42
S42D
the mutant with increased activity compared to the wild type enzyme is not phosphorylated at serine 42
T748F
the mutation increases the PDE8A1 sensitivity to several nonselective or family selective PDE inhibitors, the catalytic efficiency of the mutant is about 2fold better than that of the wild type PDE8A1
V501A
-
mutation has no significant influence on substrate affinity or specificity
D63A
the mutant shows less than 0.1% of wild type CpdA activity
H23A
the mutant shows less than 0.1% of wild type CpdA activity
N93A
the mutant shows less than 0.1% of wild type CpdA activity
additional information
additional information
-
enzyme knock-out strains show normal aggregation but impaired development from the mound stage on
additional information
enzyme knock-out strains show normal aggregation but impaired development from the mound stage on
additional information
-
generation of PDE8B KO mice, that show elevated levels of urinary corticosterone in both basal and stressed conditions compared with their littermate wild-type controls
additional information
generation of gene-deletion mutants of the high-affinity PdeH cAMP phosphodiesterase, phenotypes, overview
additional information
generation of gene-deletion mutants of the high-affinity PdeH cAMP phosphodiesterase, phenotypes, overview
additional information
generation of gene-deletion mutants of the low-affinity PdeL cAMP phosphodiesterase, phenotypes, overview
additional information
generation of gene-deletion mutants of the low-affinity PdeL cAMP phosphodiesterase, phenotypes, overview
additional information
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enzyme knock-down by RNAi reveals that it may be complemented by isoform PDEB2, but simultaneous ablation of PDEB1 and PDEB2 leads to cell death in bloodstream form trypanosomes. In vivo application of RNAi completely prevents infection and eliminates ongoing infections
additional information
enzyme knock-down by RNAi reveals that it may be complemented by isoform PDEB2, but simultaneous ablation of PDEB1 and PDEB2 leads to cell death in bloodstream form trypanosomes. In vivo application of RNAi completely prevents infection and eliminates ongoing infections
additional information
enzyme knock-down by RNAi reveals that it may be complemented by isoform PDEB2, but simultaneous ablation of PDEB1 and PDEB2 leads to cell death in bloodstream form trypanosomes. In vivo application of RNAi completely prevents infection and eliminates ongoing infections
additional information
enzyme knock-down by RNAi reveals that it may be complemented by isoform PDEB2, but simultaneous ablation of PDEB1 and PDEB2 leads to cell death in bloodstream form trypanosomes. In vivo application of RNAi completely prevents infection and eliminates ongoing infections
additional information
-
enzyme knock-down by RNAi reveals that it may be complemented by isoform PDEB1, but simultaneous ablation of PDEB1 and PDEB2 leads to cell death in bloodstream form trypanosomes. In vivo application of RNAi completely prevents infection and eliminates ongoing infections
additional information
enzyme knock-down by RNAi reveals that it may be complemented by isoform PDEB1, but simultaneous ablation of PDEB1 and PDEB2 leads to cell death in bloodstream form trypanosomes. In vivo application of RNAi completely prevents infection and eliminates ongoing infections
additional information
enzyme knock-down by RNAi reveals that it may be complemented by isoform PDEB1, but simultaneous ablation of PDEB1 and PDEB2 leads to cell death in bloodstream form trypanosomes. In vivo application of RNAi completely prevents infection and eliminates ongoing infections
additional information
enzyme knock-down by RNAi reveals that it may be complemented by isoform PDEB1, but simultaneous ablation of PDEB1 and PDEB2 leads to cell death in bloodstream form trypanosomes. In vivo application of RNAi completely prevents infection and eliminates ongoing infections
additional information
isoform PDEA1 is able to complement a yeast strain deficient in phosphodiesterase genes
additional information
-
isoform PDEA1 is able to complement a yeast strain deficient in phosphodiesterase genes
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 7
-
PdeB shows no 3',5'-cAMP phosphodiesterase activity at or below pH 6.0, PdeA and PdeB activities are strongly inhibited by 0.1 M sodium phosphate buffer (pH 6.0 and 7.0)
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50 - 55
-
heat treatment at 50°C or 55°C for 5 min slightly activates the phosphodiesterase activity of PdeB against 3',5'-cAMP by about 1.2fold of the control while PdeA activity is not activated by the heat treatment
55
-
soluble HSPDE4A10 is more thermostable (T0.5: 11 min) than the particulate enzyme (T0.5: 5 min)
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
glutathione Sepharose column chromatography, and Superdex 200 gel filtration
Ni-NTA column chromatography and Sephacryl S-200 gel filtration
recombinant His-tagged enzyme from Escherichia coli strain M15(pREP4) by nickel affinity chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cells of two human follicular thyroid carcinoma cell lines (FTC133, FTC236) are stably transfected with a cDNA encoding the PDE4A cAMP-specific phosphodiesterase (PDE) splice variant RD1 (RNPDE4A1A) so as to generate the cloned cell lines, FTC133A and FTC236A
expressed in Escherichia coli BL21 cells
expressed in Escherichia coli strain BL21
expressed in transfected COS7 cells. The human PDE4A species, h6.1 (HSPDE4A4C), which lacks the N-terminal extension of PDE-46, is an entirely soluble species when expressed in COS7 cells
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expression in Escherichia coli
expression in Escherichia coli as N-terminal glutathione S-transferase-fusion protein
expression in Sf9 insect cells
expression of PDE4B4 cDNA in COS7 cells. Treatment of COS7 cells with forskolin, to elevate cAMP levels, produced activation of PDE4B4, which is associated with the phosphorylation of PDE4B4 on Ser56 within UCR1
full coding sequence of the phosphodiesterase PDE4D1 is inserted in the bacterial expression vector pGEX-KG. N- and C-terminal truncations are also placed in the same vector, allowing the expression and purification of glutathione S-transferase (GST)-PDE fusion proteins using glutathione-Sepharose
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gene cpdA, DNA and mino acid sequenc determination and analysis, expression of His-tagged enzyme in Escherichia coli strain M15(pREP4)
TbPDE1 is expressed in Saccharomyces cerevisiae at levels that are sufficient to produce a clear phenotype (heat-shock resistance, growth as a smooth suspension), but that are too low to be detectable in PDE assay of cell lysates. The N-terminally truncated construct pET-PDE1-(Arg189-Thr620) is expressed in Escherichia coli as an active enzyme
-
the catalytic domain of human PDE4D is cloned from HL-60 cells and expressed in Escherichia coli JM109 cells
-
the DdPDE4 catalytic domain (amino acids 264-771) is expressed in vegetative AX2 cells
transient expression of the engineered human PDE4A10 open reading frame in COS7 cells allows detection of a 121000 Da protein in both soluble and particulate fractions. PDE4A10 is localized primarily to the perinuclear region of COS7 cells
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When expressed in COS-7 cells, PDE4A8 localizes predominantly in the cytosol, but 20% of the enzyme was associated with membrane fractions
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
2fold increased PDE7B mRNA expression in chronic lymphocytic leukemia correlates with a 10fold higher expression of PDE7B protein and results in an increased contribution of PDE7 to total PDE activity
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cpdA expression is positively regulated by cAMP-Vfr. cAMP-Vfr binds to the cpdA promoter region, suggesting that in vivo, cpdA transcription is directly activated by cAMP-Vfr
during cardiac hypertrophy in rats, there is a decrease in PDE4A, and PDE4B proteins and mRNA expressions
during cardiac hypertrophy in rats, there is a decrease in PDE4B protein and mRNA expressions
forskolin treatment alone is unable to stimulate mAKAP-bound PDE4D3 activity significantly in HEK-293 cells, whereas forskolin (0.05 mM) and okadaic acid (0.3 mM) treatment together synergistically increase PDE4D3 activity
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heart failure in rat induces increases in the PDE4B protein and mRNA expression
isoform PDE1C expression is highly induced in neointimal smooth muscle cells of human coronary arteries
-
isoform PDE1C expression is low in contractile smooth muscle cells but drastically elevated in synthetic smooth muscle cells in vitro and in various mouse vascular injury models in vivo
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isoforms PDE1B, PDE1C, PDE2A, PDE4A, PDE4D, PDE5A, PDE7A, PDE8A, PDE8B, PDE10A, and PDE11A show an age-related increase or decrease in mRNA expression in at least 1 of the 4 brain regions examined (hippocampus, cortex, striatum, and cerebellum). mRNA expression of isoforms PDE1A, PDE3A, PDE3B, PDE4B, PDE7A, PDE7B, and PDE9A does not change with age
Leydig cells express both PDE8A and PDE8B isoforms. The expression of PDE8B is increased in transformed Leydig cells (Leydig cell tumors-LCTs) compared to non-tumoral cells
p53 inactivates isoform PDE4D by inducing the expression of miR-139-5p which directly binds to the target sequence at 3'-UTR of PDE4D mRNA
PDE4B is upregulated in inflammatory cells from both experimental and human abdominal aortic aneurism
the cAMP-dependent transcription factor Vfr directly activates expression of cpdA in response to elevated intracellular cAMP
transcription factor Trps1 directly activates isoform Pde4d transcription
isoforms PDE1B, PDE1C, PDE2A, PDE4A, PDE4D, PDE5A, PDE7A, PDE8A, PDE8B, PDE10A, and PDE11A show an age-related increase or decrease in mRNA expression in at least 1 of the 4 brain regions examined (hippocampus, cortex, striatum, and cerebellum). mRNA expression of isoforms PDE1A, PDE3A, PDE3B, PDE4B, PDE7A, PDE7B, and PDE9A does not change with age
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isoforms PDE1B, PDE1C, PDE2A, PDE4A, PDE4D, PDE5A, PDE7A, PDE8A, PDE8B, PDE10A, and PDE11A show an age-related increase or decrease in mRNA expression in at least 1 of the 4 brain regions examined (hippocampus, cortex, striatum, and cerebellum). mRNA expression of isoforms PDE1A, PDE3A, PDE3B, PDE4B, PDE7A, PDE7B, and PDE9A does not change with age
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
refolding is initiated by addition of 0.03 mg/ml protein to a buffer of 0.5 M Tris-HCl pH 7.0, 20 mM MgCl2, 20 mM MnCl2, 0.020 mM ZnSO4, 0.7 M arginine, 30% glycerol, 10 mM NaCl, 1 mM KCl, and 10 mM dithiothreitol, at 4°C for three days
refolding to active enzyme from inclusion bodies requires high concentrations of arginine hydrochloride, ethylene glycol, and magnesium chloride at pH 8.5
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
agriculture
-
the enzyme is indispensable for key biological processes of Sclerotinia sclerotiorum and can potentially serve as a host-induced gene silencing (HIGS) target to control stem rot in the field
medicine
molecular biology
medicine
-
PDE4 may be of particular importance as an antidepressant target in that it is regulated by repeated treatment with both norepinephrine and serotonin reuptake inhibitors as well as by the PDE4 inhibitor rolipram
medicine
-
expression of phosphodiesterases PDE1A, PDE1C, PDE3B, and PDE5A is enhanced in pulmonary arterial smooth muscle cells from both patients with idiopathic pulmonary arterial hypertension or secondary pulmonary hypertension compared with control. Increase in phosphodiesterase isoforms, particularly in PDE1C, contributes to decreased cAMP levels and increased proliferation of pulmonary arterial smooth muscle cells in patients with pulmonary hypertension
medicine
enzyme knock-down by RNAi reveals that it may be complemented by isoform PDEB2, but simultaneous ablation of PDEB1 and PDEB2 leads to cell death in bloodstream form trypanosomes. In vivo application of RNAi completely prevents infection and eliminates ongoing infections
medicine
enzyme knock-down by RNAi reveals that it may be complemented by isoform PDEB1, but simultaneous ablation of PDEB1 and PDEB2 leads to cell death in bloodstream form trypanosomes. In vivo application of RNAi completely prevents infection and eliminates ongoing infections
medicine
-
statistically significnat differences between cAMP-dependent phosphodiesterase activity in benign tumours and healthy control. Enzymatic activity in tumour groups analysed such as Warthin's tumour, pleomorphic adenoma. Or myoepithelioma, is about 50% lower than in control
medicine
interactions of PDE4D5 with both the N- and C-terminal domains of beta-arrestin are essential for beta2-adrenoceptor regulation
medicine
-
enzyme variants PDE4B and/or PDE4D regulate cell growth through cAMP targets in the HMG malignant melanoma cell
medicine
-
reactive oxygen-species mediated lung inflammation may be mediated at least in part by calcium and elevated enzyme activity associated with decreased caMP in both macorphages and epithelial cells
medicine
-
reactive oxygen-species mediated lung inflammation may be mediated at least in part by calcium and elevated enzyme activity associated with decreased caMP in both macorphages and epithelial cells
medicine
TbrPDEB1 and TbrPDEB2 are essential for virulence, making them valuable potential targets for new PDE-inhibitor based trypanocidal drugs
medicine
-
PDE5 inhibition improved short-term object recognition performance after an acute tryptophan depletion induced deficit
medicine
-
PDE5 inhibition is a efficacious oral therapy for erectile dysfunction
medicine
-
phosphodiesterase 4B mediates Streptococcus pneumoniae-induced mucin gene MUC5AC up-regulation by inhibiting the expression of a negative regulator MKP-1, which in turn leads to enhanced MAPK ERK activation and subsequent up-regulation of MUC5AC. PDE4B inhibits MKP-1 expression in a cAMP-PKA-dependent manner. PDE4-specific inhibitor rolipram inhibits Streptomyces pneumoniae-induced MUC5AC up-regulation both in vitro and in vivo. PDE4B plays a critical role in MUC5AC induction. Topical and post-infection administration of rolipram into the middle ear potently inhibits Streptomyces pneumoniae-induced MUC5AC up-regulation
molecular biology
-
convenient and sensitive radioenzymatic assay for characterization and determining the contribution if the various PDE families in cell and tissue, PDE4
molecular biology
-
convenient and sensitive radioenzymatic assay for characterization and determining the contribution if the various PDE families in cell and tissue, PDE7
molecular biology
-
convenient and sensitive radioenzymatic assay for characterization and determining the contribution if the various PDE families in cell and tissue, PDE8
molecular biology
development of cell-permeable peptide reagents based upon the N-terminal region of PDE4D5 that allow for the selective disruption of PDE4D5 targeting to specific signalling scaffolds, namely beta-arrestin and RACK1
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