Information on EC 3.1.4.17 - 3',5'-cyclic-nucleotide phosphodiesterase

Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
3.1.4.17
-
RECOMMENDED NAME
GeneOntology No.
3',5'-cyclic-nucleotide phosphodiesterase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
nucleoside 3',5'-cyclic phosphate + H2O = nucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
nucleoside 3',5'-cyclic phosphate + H2O = nucleoside 5'-phosphate
show the reaction diagram
mechanism
P0A8Z7
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Purine metabolism
-
SYSTEMATIC NAME
IUBMB Comments
3',5'-cyclic-nucleotide 5'-nucleotidohydrolase
Acts on 3',5'-cyclic AMP, 3',5'-cyclic dAMP, 3',5'-cyclic IMP, 3',5'-cyclic GMP and 3',5'-cyclic CMP.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
3',5'-cyclic nucleoside monophosphate phosphodiesterase
-
-
-
-
3',5'-cyclic nucleotide phosphodiesterase 11A
-
-
3',5'-cyclonucleotide phosphodiesterase
-
-
-
-
3',5'-nucleotide phosphodiesterase
-
-
-
-
3':5'-CNP
-
-
-
-
3':5'-cyclic nucleotide 5'-nucleotidohydrolase
-
-
-
-
61 kDa Cam-PDE
-
-
-
-
63 kDa Cam-PDE
-
-
-
-
Ca2+/calmodulin-dependent cyclic nucleotide phosphodiesterase
-
-
Ca2+/calmodulin-stimulated phosphodiesterase
-
-
calmodulin-dependent cyclic nucleotide phosphodiesterase
-
-
Cam-PDE 1A
-
-
-
-
Cam-PDE 1B
-
-
-
-
Cam-PDE 1C
-
-
-
-
cAMP phosphodiesterase
-
-
cAMP-PDE
-
-
cAMP-specific PDE
-
-
CaMPDE
-
-
CGB-PDE
-
-
-
-
CGIP1
-
-
-
-
CGIPDE1
-
-
-
-
cGMP-binding cGMP-specific phosphodiesterase
-
-
-
-
cGMP-inhibited PDE
-
-
CGS-PDE
-
-
-
-
cGSPDE
-
-
-
-
class II 3,5-cyclic nucleotide phosphodiesterase
-
-
cyclic 3',5'-mononucleotide phosphodiesterase
-
-
-
-
cyclic 3',5'-nucleotide phosphodiesterase
-
-
-
-
cyclic 3',5'-phosphodiesterase
-
-
-
-
cyclic 3',5-nucleotide monophosphate phosphodiesterase
-
-
-
-
Cyclic GMP stimulated phosphodiesterase
-
-
-
-
cyclic nucleotide phosphodiesterase
-
-
-
-
cyclic nucleotide phosphodiesterase
-, C7DXW3, C7DXW4, C7DXW5, C7DXW6, C7DXW7
-
cyclic nucleotide phosphodiesterase
-
-
cyclic nucleotide phosphodiesterase 10A
-
-
cyclic nucleotide phosphodiesterase 3B
-
-
cyclic nucleotide phosphodiesterase PDE3
-
-
cyclic nucleotide phosphodiesterase type 1
-
-
DPDE1
-
-
-
-
DPDE2
-
-
-
-
DPDE3
-
-
-
-
DPDE4
-
-
-
-
dual-specificity PDE
-
-
dual-specificity PDE
-
-
Dunce protein
-
-
-
-
GMP-PDE alpha
-
-
-
-
GMP-PDE beta
-
-
-
-
GMP-PDE delta
-
-
-
-
GMP-PDE gamma
-
-
-
-
h-prune
-
-
HCP1
-
-
-
-
High-affinity cAMP phosphodiesterase
-
-
-
-
Learning/ memory process protein
-
-
-
-
Low-affinity cAMP phosphodiesterase
-
-
-
-
MMPDE8
-
-
-
-
nucleoside 3',5'-cyclic phosphate diesterase
-
-
-
-
nucleoside-3',5-monophosphate phosphodiesterase
-
-
-
-
p17 protein
-
-
-
-
P2A
-
-
-
-
PDE V-B1
-
-
-
-
PDE V-C1
-
-
-
-
PDE1
-
-
PDE1
-
isoform
PDE1
P54750, Q01064
-
PDE1
-
-
PDE1
Rattus norvegicus Sprague-Dawley
-
-
-
PDE10
-
-
PDE10A
-
hydrolyses both 3',5'-cAMP and 3',5'-cGMP although with different kinetic parameters
PDE10A
Q9Y233
-
PDE10A
-
hydrolyses both 3',5'-cAMP and 3',5'-cGMP although with different kinetic parameters
PDE11
-
-
PDE11A
-
isoform
PDE11A
-
-
PDE11A
-
4 splice variants PDE11A1 -PDE11A4
PDE11A
Q9HCR9
-
PDE11A1
-
-
PDE11A2
-
-
PDE11A3
-
-
PDE1A
-
-
PDE1A
P54750
-
PDE1A
P54750
isoform
PDE1A_v7
-
-
PDE1B
-
-
PDE1B
Q01064
-
PDE1B
Q01064
isoform
PDE1C
-
-
PDE1C
Q14123
-
PDE2
-
isoform
PDE2
O00408
-
PDE21
-
-
-
-
PDE2A
-
-
PDE2A
O00408
-
PDE2A
O00408
isoform
PDE2A1
-
-
PDE2A2
-
-
PDE2A3
-
-
PDE3
-
-
PDE32
-
-
-
-
PDE3A
-
-
PDE3A
C7DXW3
isoform
PDE3A
-
isoform
PDE3A
Q14432
-
PDE3A
-
-
PDE3B
-
-
PDE3B
-
-
PDE3B
Q13370
-
PDE4
-
-
PDE43
-
-
-
-
PDE46
-
-
-
-
PDE4D
C7DXW4
isoform
PDE5
-
-
PDE8A
C7DXW5
isoform
PDE8B
C7DXW6
isoform
PDE9A
C7DXW7
isoform
PdeA
-
has 3',5'- and 2',3'-cAMP phosphodiesterase and phosphomonoesterase activities
PDEase
-
-
-
-
PDEase regA
-
-
-
-
PdeB
-
has 3',5'- and 2',3'-cAMP phosphodiesterase and phosphomonoesterase activities
PDEI
-
-
phosphodiesterase 1
-
-
phosphodiesterase 1
-
-
phosphodiesterase 1
Rattus norvegicus Sprague-Dawley
-
-
-
phosphodiesterase 10
-
-
phosphodiesterase 10A
-
-
phosphodiesterase 11
-
-
phosphodiesterase 2
-
-
phosphodiesterase 2
-
-
phosphodiesterase 3
-
-
phosphodiesterase type 3A
-
-
phosphodiesterase, cyclic 3',5'-nucleotide
-
-
-
-
phosphodiesterase-10A
-
-
phosphodiesterase-1B
-
-
phosphodiesterase-3
-
-
Rv0805 protein
-
-
TM22
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9040-59-9
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
calf
-
-
Manually annotated by BRENDA team
guinea pig
-
-
Manually annotated by BRENDA team
isoform PDE1
-
-
Manually annotated by BRENDA team
isoform PDE3a, fragment; guinea pig
UniProt
Manually annotated by BRENDA team
isoform PDE4d, fragment; guinea pig
UniProt
Manually annotated by BRENDA team
isoform PDE8a, fragment; guinea pig
UniProt
Manually annotated by BRENDA team
isoform PDE8b, fragment; guinea pig
UniProt
Manually annotated by BRENDA team
isoform PDE9a, fragment; guinea pig
UniProt
Manually annotated by BRENDA team
isoforms PDE1, PDE2, PDE3, PDE7
-
-
Manually annotated by BRENDA team
computational analysis
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
isoform PDE1
-
-
Manually annotated by BRENDA team
isoform PDE10A1
SwissProt
Manually annotated by BRENDA team
isoform PDE11
-
-
Manually annotated by BRENDA team
isoform PDE11A4
SwissProt
Manually annotated by BRENDA team
isoform PDE1B2
-
-
Manually annotated by BRENDA team
isoform PDE1C
-
-
Manually annotated by BRENDA team
isoforms PDE2A, PDE3A
-
-
Manually annotated by BRENDA team
isoforms PDE3, PDE1A
-
-
Manually annotated by BRENDA team
isozyme PDE11A2; isozyme PDE11A3
SwissProt
Manually annotated by BRENDA team
PDE10A
SwissProt
Manually annotated by BRENDA team
PDE11A
SwissProt
Manually annotated by BRENDA team
PDE1; PDE11; PDE2
-
-
Manually annotated by BRENDA team
PDE1C
UniProt
Manually annotated by BRENDA team
PDE3A
UniProt
Manually annotated by BRENDA team
PDE3B
UniProt
Manually annotated by BRENDA team
splice variants A1, A2, A3, A4 of isoform PDE11
-
-
Manually annotated by BRENDA team
overview on PDE1 isozymes
-
-
Manually annotated by BRENDA team
isoform PDE1
-
-
Manually annotated by BRENDA team
isozymes PDE1A, PDE1B, PDE1C
-
-
Manually annotated by BRENDA team
; product of Rv0805 gene
-
-
Manually annotated by BRENDA team
product of Rv0805 gene
O06629
Uniprot
Manually annotated by BRENDA team
gene pdeE
-
-
Manually annotated by BRENDA team
isoforms PdeA, PdeB, PdeC
-
-
Manually annotated by BRENDA team
isoform PDE1
-
-
Manually annotated by BRENDA team
isoform PDE1A
-
-
Manually annotated by BRENDA team
isoform PDE2
-
-
Manually annotated by BRENDA team
isoforms PDE1, PDE2, PDE3, PDE10, PDe11
-
-
Manually annotated by BRENDA team
isozyme PDE11A
-
-
Manually annotated by BRENDA team
two PDE3 isoforms
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
Sinorhizobium fredii MAR-1
MAR-1
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
inhibition of PDE1 is involved in the cGMP-dependent protein kinase-mediated vasorelaxant effect of dioclein in human saphenous vein
malfunction
-
phosphodiesterase-1 inhibition decreases vascular contraction in arteries from angiotensin II hypertensive, but not control, rats. The inhibition of PDE1 in smooth muscle cells isolated from normal aorta or from atherosclerotic lesions results in suppression of smooth muscle cell proliferation
malfunction
-
pdeE mutant exhibits delays in fruiting body and spore formation compared with the wild type when cultured on starvation medium. It also shows reduced enzyme activity
malfunction
Rattus norvegicus Sprague-Dawley
-
phosphodiesterase-1 inhibition decreases vascular contraction in arteries from angiotensin II hypertensive, but not control, rats. The inhibition of PDE1 in smooth muscle cells isolated from normal aorta or from atherosclerotic lesions results in suppression of smooth muscle cell proliferation
-
physiological function
-
when Ca2 is high, PDE1 is activated, resulting in lower levels of cGMP, which theoretically facilitates the smooth muscle cell contraction
physiological function
-
PDE3A physically and functionally interacts with cystic fibrosis transmembrane conductance regulator, CFTR, channel. PDE3A inhibition generates compartmentalized cAMP, which further clusters PDE3A and CFTR into microdomains at the plasma membrane and potentiates CFTR channel function. Actin skeleton disruption reduces PDE3A-CFTR interaction and segregates PDE3A from its interacting partners, thus compromising the integrity of the CFTR-PDE3A-containing macromolecular complex, compartmentalized cAMP signaling is lost
physiological function
-
in erythrocytes, PDE3 selectively regulates cAMP synthesis stimulates by activation of the IP receptor. The isoform of PDE1 present in these erythrocytes is primarily involved in hydrolysis of cGMP. 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
Rattus norvegicus Sprague-Dawley
-
when Ca2 is high, PDE1 is activated, resulting in lower levels of cGMP, which theoretically facilitates the smooth muscle cell contraction
-
metabolism
-
in adipocytes, insulin induces formation of macromolecular complexes containing signaling molecules such as IRS-1, PI3K and PKB, proteins involved in PDE3B activation/phosphorylation
additional information
-
three different isoforms of calmodulin-dependent PDE isoforms are reported, PDE1A and PDE1B, which display higher affinity to hydrolyze cGMP compared to cAMP, and PDE1C, which has a similar ability to hydrolyze cGMP and cAMP
additional information
Rattus norvegicus Sprague-Dawley
-
three different isoforms of calmodulin-dependent PDE isoforms are reported, PDE1A and PDE1B, which display higher affinity to hydrolyze cGMP compared to cAMP, and PDE1C, which has a similar ability to hydrolyze cGMP and cAMP
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2',3'-cAMP + H2O
3'-AMP
show the reaction diagram
-
in PdeB the phosphodiesterase activity for 2',3'-cAMP is about 1.7fold higher than that for 3',5'-cAMP
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
C7DXW3, C7DXW4, C7DXW5, C7DXW6, C7DXW7, -
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
P27815
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
O00408, P54750, Q01064
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
inhibition of cAMP hydrolysis by cGMP is likely to contribute to cGMP-mediated signaling in myocardium
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
activity with 3',5'-cGMP and 3',5'-cAMP is nearly identical, PDE11, activity with 3',5'-cGMP and 3',5'-cAMP is nearly identical, PDE2, activity with 3',5'-cGMP is higher than with 3',5'-cAMP
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
maximal velocity for cAMP is 4fold to 10fold higher than for cGMP, PDE11A4
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
specific for 3',5'-cGMP and 3',5'-cAMP, PDE1, specific for 3',5'-cGMP and 3',5'-cAMP, PDE11
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
3',5'-cAMP is completely hydrolyzed to adenosine when incubated with PdeA for a prolonged time
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
3',5'-cAMP is predominantly hydrolyzed by PDE3A
-
-
?
3',5'-cAMP + H2O
adenosine 5'-phosphate
show the reaction diagram
-
PDE1, PDE2, PDE3A, PDE3B
-
-
?
3',5'-cCMP + H2O
5'-CMP
show the reaction diagram
-
-
-
-
?
3',5'-cCMP + H2O
5'-CMP
show the reaction diagram
-
-
-
-
?
3',5'-cdAMP + H2O
5'-dAMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
C7DXW3, C7DXW4, C7DXW5, C7DXW6, C7DXW7, -
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
Q01064
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
P27815
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
O00408, P54750, Q01064
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
PDE1 and PDE2 are the main PDEs that act to degrade cGMP in methacholine-stimulated cells
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
activity with 3',5'-cGMP and 3',5'-cAMP is nearly identical, PDE11, activity with 3',5'-cGMP and 3',5'-cAMP is nearly identical, PDE2, activity with 3',5'-cGMP is higher than with 3',5'-cAMP
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
maximal velocity for cAMP is 4fold to 10fold higher than for cGMP, PDE11A4
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
specific for 3',5'-cGMP and 3',5'-cAMP, PDE1, specific for 3',5'-cGMP and 3',5'-cAMP, PDE11
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
the technique can be used to measure Ca2+/CaM-stimulated PDE activity in cultured cells or tissues
-
-
?
3',5'-cGMP + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
guanosine 5'-phosphate
show the reaction diagram
-
PDE1, PDE3A, PDE3B
-
-
?
3'-AMP + H2O
?
show the reaction diagram
-
high activity
-
-
?
3'-GMP + H2O
?
show the reaction diagram
-
high activity
-
-
?
5'-ATP + H2O
?
show the reaction diagram
-
-
-
-
?
5'-dAMP + H2O
?
show the reaction diagram
-
low activity
-
-
?
5'-UMP + H2O
?
show the reaction diagram
-
high activity
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
cAMP + H2O
AMP
show the reaction diagram
-
-
-
?
cAMP + H2O
AMP
show the reaction diagram
-
-
-
?
cAMP + H2O
AMP
show the reaction diagram
-
-
-
?
cAMP + H2O
AMP
show the reaction diagram
Q9HCR9
-
-
?
cAMP + H2O
AMP
show the reaction diagram
Sinorhizobium fredii MAR-1
-
-
-
?
cAMP + H2O
5'-AMP
show the reaction diagram
-
degradation of extracellular cAMP by isoforms PDE1, PDE7. Degradation of intracellular cAMP by isoform PDE2
-
-
?
cGMP + H2O
GMP
show the reaction diagram
-
-
-
?
cGMP + H2O
GMP
show the reaction diagram
-
-
-
?
cGMP + H2O
GMP
show the reaction diagram
-
-
-
?
cGMP + H2O
GMP
show the reaction diagram
Q9HCR9
-
-
?
cGMP + H2O
GMP
show the reaction diagram
Sinorhizobium fredii MAR-1
-
-
-
?
cGMP + H2O
5'-GMP
show the reaction diagram
-
degradation of intracellular cGMP by isoform PDE3
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
Q01064
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
?
UDP-D-glucose + H2O
?
show the reaction diagram
-
UDP-D-glucose is hydrolyzed by PdeB, but not by PdeA
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
Rattus norvegicus Sprague-Dawley
-
-
-
-
?
additional information
?
-
-
not: 2',3'-cAMP
-
-
-
additional information
?
-
-
not: 2',3'-cAMP
-
-
-
additional information
?
-
-
overview on physiological role
-
?
additional information
?
-
-
h-prune activity is suppressed by dipyridamole and enhanced by the interaction with nm23-H1. Activity is involved in promoting cancer metastasis
-
-
-
additional information
?
-
-
insulin-induced activation of the membrane bound PDE3B is a key step in insulin-mediated inhibition of lipolysis and is also involved in the regulation of insulin-mediated glucose uptake and lipogenesis in adipocytes
-
-
-
additional information
?
-
-
muscarinic antagonists acting possibly as inverse agonists on M2/M3 muscarinic acetylcholine receptors anchored to sarcolemma membranes can initiate a new signal transducing cascade leading to inhibition of PDEI, which produces a simultaneous rise in both cAMP and cGMP intracellular levels in tracheal smooth muscle
-
-
-
additional information
?
-
-
PDE1 in Pukinje neurons may play a role in limiting the cGMP-mediated long-term depression response
-
-
-
additional information
?
-
-
PDE1A is involved in cGMP breakdown in parotid acinar cells of Oryctolagus cuniculus
-
-
-
additional information
?
-
Q61481
PDE1A_v7 is the major form of cyclic nucleotide phosphodiesterase 1A expressed in mature sperm and is therefore likely to play an important role in cyclic nucleotide regulation of mature sperm function
-
-
-
additional information
?
-
-
real-time monitoring of PDE2 activity by a fluorescent cAMP sensor shows that activation of PDE2 results in a rapid decrease of intracellular cAMP from high micromolar to sub-micromolar range within a few seconds. High catalytic activity and fast action in regulating cAMP signaling in a physiological system
-
-
-
additional information
?
-
-
Rv0805 protein could have an important role to play in regulating cAMP levels in Mycobacterium tuberculosis
-
-
-
additional information
?
-
-
the enzyme might be involved in multiple physiological processes in various organs via its ability to modulate intracellular cAMP and cGMP levels
-
-
-
additional information
?
-
Q01062
cGMP levels in the spinal cord are controlled by a number of enzyme isoforms, that can be present in the same cell. Role of NO-cGMP signaling in nociceptive processing
-
-
-
additional information
?
-
-
cytoplasmic isoform PDE1A regulates myosin light chain phosphorylation with little effect on apoptosis, whereas nuclear enzyme isoform PDE1A is important in vascular smoth muscle cell growth and survival
-
-
-
additional information
?
-
-
isoform PDE1B2 predominantly regulates cGMP and plays a lesser role in cAMP regulation in response to cyclase agonists
-
-
-
additional information
?
-
Q01065
isoform PDE2 regulates the basal cGMP concentration in thalamic neuron
-
-
-
additional information
?
-
-
the effect of increasing concentrations of cGMP on endothelial permeability is biphasic, attributable to the relative amounts of enzyme isoforms PDE2A and PDE3A in endothelial cells
-
-
-
additional information
?
-
-
isoforms PDE1 and PDE7 are dual-specificity enzymes with negative cooperativity and very different kinetics. Both have 2-3fold lower affinity for cGMP than for cAMP
-
-
-
additional information
?
-
-
splice variants PDE11A1 and PDE11A2 show higher affinity for cAMP and cGMP than PDE11A4
-
-
-
additional information
?
-
-
PDE10A regulates both cAMP and cGMP signaling cascades to impact early signal processing in the corticostriatothalamic circuit
-
-
-
additional information
?
-
-
3',5'-cGMP is either not hydrolysed or is cleaved very slowly by PdeA and PdeB, PdeA and PdeB show no activities toward 2'-AMP and 2'-GMP
-
-
-
additional information
?
-
-
NAD+ is not a substrate of PDE3A
-
-
-
additional information
?
-
-
PdeA and PdeB 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
-
-
-
additional information
?
-
-
PDE3A physically and functionally interacts with cystic fibrosis transmembrane conductance regulator, CFTR, channel
-
-
-
additional information
?
-
-
structure analysis of phosphodiesterase 10 binding with cAMP and cGMP by hybrid quantum mechanical/molecular mechanical calculations using cyrstal structures of the substrate-bound enzyme, detailed overview
-
-
-
additional information
?
-
-
PDE2 can hydrolyze both cAMP and cGMP with similar maximal rates. PDE1A prefers cGMP, PDE1B cAMP, and PDE1C hydrolyzes both substrates equally. The PDE3 family can hydrolyze both cAMP and cGMP
-
-
-
additional information
?
-
-
substrate specificity of PdeE, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
C7DXW3, C7DXW4, C7DXW5, C7DXW6, C7DXW7, -
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
inhibition of cAMP hydrolysis by cGMP is likely to contribute to cGMP-mediated signaling in myocardium
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
C7DXW3, C7DXW4, C7DXW5, C7DXW6, C7DXW7, -
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
PDE1 and PDE2 are the main PDEs that act to degrade cGMP in methacholine-stimulated cells
-
-
?
additional information
?
-
-
overview on physiological role
-
?
additional information
?
-
-
h-prune activity is suppressed by dipyridamole and enhanced by the interaction with nm23-H1. Activity is involved in promoting cancer metastasis
-
-
-
additional information
?
-
-
insulin-induced activation of the membrane bound PDE3B is a key step in insulin-mediated inhibition of lipolysis and is also involved in the regulation of insulin-mediated glucose uptake and lipogenesis in adipocytes
-
-
-
additional information
?
-
-
muscarinic antagonists acting possibly as inverse agonists on M2/M3 muscarinic acetylcholine receptors anchored to sarcolemma membranes can initiate a new signal transducing cascade leading to inhibition of PDEI, which produces a simultaneous rise in both cAMP and cGMP intracellular levels in tracheal smooth muscle
-
-
-
additional information
?
-
-
PDE1 in Pukinje neurons may play a role in limiting the cGMP-mediated long-term depression response
-
-
-
additional information
?
-
-
PDE1A is involved in cGMP breakdown in parotid acinar cells of Oryctolagus cuniculus
-
-
-
additional information
?
-
Q61481
PDE1A_v7 is the major form of cyclic nucleotide phosphodiesterase 1A expressed in mature sperm and is therefore likely to play an important role in cyclic nucleotide regulation of mature sperm function
-
-
-
additional information
?
-
-
real-time monitoring of PDE2 activity by a fluorescent cAMP sensor shows that activation of PDE2 results in a rapid decrease of intracellular cAMP from high micromolar to sub-micromolar range within a few seconds. High catalytic activity and fast action in regulating cAMP signaling in a physiological system
-
-
-
additional information
?
-
-
Rv0805 protein could have an important role to play in regulating cAMP levels in Mycobacterium tuberculosis
-
-
-
additional information
?
-
-
the enzyme might be involved in multiple physiological processes in various organs via its ability to modulate intracellular cAMP and cGMP levels
-
-
-
additional information
?
-
Q01062
cGMP levels in the spinal cord are controlled by a number of enzyme isoforms, that can be present in the same cell. Role of NO-cGMP signaling in nociceptive processing
-
-
-
additional information
?
-
-
cytoplasmic isoform PDE1A regulates myosin light chain phosphorylation with little effect on apoptosis, whereas nuclear enzyme isoform PDE1A is important in vascular smoth muscle cell growth and survival
-
-
-
additional information
?
-
-
isoform PDE1B2 predominantly regulates cGMP and plays a lesser role in cAMP regulation in response to cyclase agonists
-
-
-
additional information
?
-
Q01065
isoform PDE2 regulates the basal cGMP concentration in thalamic neuron
-
-
-
additional information
?
-
-
the effect of increasing concentrations of cGMP on endothelial permeability is biphasic, attributable to the relative amounts of enzyme isoforms PDE2A and PDE3A in endothelial cells
-
-
-
additional information
?
-
-
PDE10A regulates both cAMP and cGMP signaling cascades to impact early signal processing in the corticostriatothalamic circuit
-
-
-
additional information
?
-
-
PDE3A physically and functionally interacts with cystic fibrosis transmembrane conductance regulator, CFTR, channel
-
-
-
additional information
?
-
-
structure analysis of phosphodiesterase 10 binding with cAMP and cGMP by hybrid quantum mechanical/molecular mechanical calculations using cyrstal structures of the substrate-bound enzyme, detailed overview
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
Calmodulin
-
;
Calmodulin
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ba2+
-
40% stimulation at 0.25 mM
Ca2+
-
40% stimulation at 0.25 mM
Ca2+
-
Ca2+/calmodulin dependent
Ca2+
-
Ca2+/calmodulin stimulated
Ca2+
-
Ca2+/calmodulin stimulated
Ca2+
-
-
Ca2+
-
Ca2+/calmodulin stimulated
Ca2+
-
Ca2+/calmodulin dependent
Ca2+
-
Ca2+/calmodulin dependent
Ca2+
Q01064
Ca2+/calmodulin stimulated
Ca2+
-
Ca2+/calmodulin dependent
Ca2+
-
stimulation of phosphodiesterase II
Ca2+
-
differential effect on isozymes, activation only in complex with calimodulin, overeview
Ca2+
-
Ca2+/calmodulin-dependent enzyme
Ca2+
-
isoform PDE1B2 activity can be regulated by changes in Ca2+ levels
Ca2+
-
Ca2+ activates; Ca2+ activates
Ca2+
-
activates in vivo
CaCl2
-
entirely dependent on the presence of divalent cations, activity with 0.2 mM CaCl2 is 15.9% of maximal activity obtained with 2 mM MgCl2
Co2+
-
stimulates at 2.5 mM
Co2+
-
stimulates
Co2+
-
can substitute for Mg2+
Co2+
-
the enzyme activities of PdeA and PdeB in the hydrolysis of 3',5'-cAMP are stimulated 3.2fold and 1.98fold at pH 8.0 in 50 mM Tris-HCl buffer by the addition of Co2+ at 0.05 mM, respectively
Co2+
-
required, activates
Cu2+
-
stimulates at 2.5 mM
Fe3+
P0A8Z7
required
Mg2+
-
stimulates at 2.5 mM
Mg2+
-
required
Mg2+
-
stimulates
Mg2+
-
dependent on
Mg2+
-
dependent on; stimulates
Mg2+
-
dependent on
Mg2+
-
required
Mg2+
-
entirely dependent on the presence of divalent cations, maximal activity with 2 mM MgCl2
Mg2+
-
is coordinated to Asp564, two phosphate oxygen atoms, and three water molecules
Mn2+
-
stimulates at 2.5 mM
Mn2+
-
required
Mn2+
-
stimulates
Mn2+
-
can substitute for Mg2+
Mn2+
-
Km value and Hill constant for wild-type 0.021 mM and 1, respectively, for mutant D21A 0.021 mM and 4.1, respectively, for mutant H23A 0.053 mM and 1, respectively, for mutant D66A, 0.072 and 6.4, respectively, for mutant H169A 0.022 and 1.7, respectively, for mutant H207A, 0.062 and 3.1, respectively
Mn2+
-
entirely dependent on the presence of divalent cations, activity with 2 mM MnCl2 is 53.5% of maximal activity obtained with 2 mM MgCl2
Mn2+
-
the enzyme activities of PdeA and PdeB in the hydrolysis of 3',5'-cAMP are stimulated 4fold and 2.14fold at pH 8.0 in 50 mM Tris-HCl buffer by the addition of Mn2+ at 0.05 mM, respectively
Zn2+
-
entirely dependent on the presence of divalent cations, activity with 0.03 mM ZnCl2 is 19.5% of maximal activity obtained with 2 mM MgCl2
Zn2+
-
is coordinated to His529, His563, Asp564, Asp674, and two phosphate oxygen atoms
Mn2+
-
required, activates
additional information
-
-
additional information
-
no metal ion required
additional information
P0A8Z7
requires a divalent metal ion
additional information
-
no metal ion requirement
additional information
-
no effect on enzyme activity by Mg2+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(-)-6-(3-(3-cyclopropyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.0001 mM, PDE3A; IC50: 0.00028 mM, PDE3B
(2R,3R)-3-(6-amino-9H-purin-9-yl)nonan-2-ol
-
IC50: 0.0043 mM, PDE2
(2S,3R)-3-(7-amino-3H-imidazo[4,5-b]pyridin-3-yl)nonan-2-ol
-
-
(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: 0.000006 mM, PDE3; IC50: 0.0012 mM, PDE2; IC50: 0.015 mM, PDE1
(6aS,9aR)-3-benzyl-2-(biphenyl-4-ylmethyl)-5-methyl-5,6a,7,8,9,9a-hexahydrocyclopenta[4,5]imidazo[2,1-b]purin-4(3H)-one
-
comparison of inhibitory effect on several recombinant human PDE isoforms. Effective PDE1 inhibitor in cellular context
(Rp)-guanosine-3',5'-cyclic-S-(4-bromo-2,3-dioxobutyl)monophosphorothioate
-
time-dependent and irreversible inactivation of PDE3A
1-(2-methylbenzyl)-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)-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-(3-methylbenzyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
1-(4-chlorobenzyl)-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)-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
-
-
1-benzyl-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
-
IC50: 0.00000034 mM, PDE3A, highly selective PDE3 inhibitor; IC50: 0.0000019 mM, PDE3B; IC50: 0.0.0209 mM, PDE2; IC50: 0.1129 mM, PDE1
2-[[4-[4-pyridin-4-yl-1-(2,2, 2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline succinic acid
-
potent inhibitor
-
2-[[4-[4-pyridin-4-yl-1-(2,2, 2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline succinic acid
-
selective PDE10A inhibitor, inhibition of striatal PDE10A activity increases the responsiveness of medium-sized spiny projection neurons to depolarising stimuli
-
3',5'-cGMP
-
-
3'-benzyl-2'-(biphenyl-4-ylmethyl)-5'-methyl-3'H-spiro[cyclopentane-1,7'-imidazo[2,1-b]purin]-4'(5'H)-one
-
comparison of inhibitory effect on several recombinant human PDE isoforms. Effective PDE1 inhibitor in cellular context
3-isobutyl-1-methyl-1H-purine-2,6(3H,7H)-dione
-
IC50: 0.0402 mM
3-isobutyl-1-methyl-1H-purine-2,6(3H,7H)-dione
-
IC50: 0.068 mM
3-isobutyl-1-methyl-1H-purine-2,6(3H,7H)-dione
-
IC50: 0.02654 mM, PDE4A4
3-isobutyl-1-methylxanthine
-
-
3-isobutyl-1-methylxanthine
-
marked differences in inhibition for isozymes
3-isobutyl-1-methylxanthine
-
broad-spectrum PDE inhibitor; broad-spectrum PDE inhibitor; broad-spectrum PDE inhibitor
3-isobutyl-8-(methoxymethyl)-1-methyl-3,9-dihydro-1H-purine-2,6-dione
-
i.e. 8MM-IBMX, comparison of inhibitory effect on several recombinant human PDE isoforms
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
-
Ro20-1724
5-(2-propoxyphenyl)-2,3-dihydro-7H-[1,2,3]triazolo[4,5-d]pyrimidin-7-one
-
-
5-(3-cyclopentyloxy-4-methoxy-phenyl)-pyrrolidin-2-one
-
50% inhibition at about 0.1 mM
5-methyl-2-[4-(trifluoromethyl)benzyl]-5,6a,7,8,9,9a-hexahydrocyclopenta[4,5]imidazo[2,1-b]purin-4(1H)-one
-
i.e. SCH51866, comparison of inhibitory effect on several recombinant human PDE isoforms. Effective PDE1 inhibitor in cellular context
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.00000032 mM, PDE3A, highly selective PDE3 inhibitor; IC50: 0.0000015 mM, PDE3B; IC50: 0.0429 mM, PDE1; IC50: 0.0523 mM, PDE2
8-methoxymethyl(-3-isobutyl-1-)methylxanthine
Q01064
-
8-methoxymethyl(-3-isobutyl-1-)methylxanthine
-
-
8-methoxymethyl-3-isobutyl-1-methylxanthine
-
-
8-methoxymethyl-3-isobutyl-1-methylxanthine
-
0.02 mM selectively inhibits PDE1; 0.02 mM selectively inhibits PDE1
8-methoxymethyl-isobutylmethylxanthine
-
inhibits activated PDE1 and PDE2 isoforms as well as PDE4 and PDE5, is 3times more potent in inhibiting PDE5 than PDE1
adenine
-
at 2.5 mM, strong
adenosine
-
at 2.5 mM, strong
ADP
-
at 2.5 mM, strong
Al3+
-
strongly inhibitory at 2.5 mM
amantadine
-
brain 60 kDa isozyme
AMP
-
at 2.5 mM, strong
amrinone
-
IC50: 0.0167 mM, PDE3A; IC50: 0.0312 mM, PDE3B
Angiotensin III
-
-
apigenin
-
IC50: 0.0105 mM, PDB3; IC50: 0.0167 mM, PDB2; IC50: 0.0254 mM, PDB1
ATP
-
at 2.5 mM, strong
BAY 60-7550
-
PDE2 inhibitor
BAY60-7550
Q01065
inhibition of isoform PDE2, results in increase in basal cGMP levels after application to thalamic neurons
Biochanin A
-
IC50: 0.0279 mM, PDE2; IC50: 0.0291 mM, PDE1
Ca2+
-
micromolar concentrations
Caffeine
-
noncompetitive, dog heart
Caffeine
-
-
Calmidazolium
-
soluble but not particulate form
cAMP
-
particulate enzyme
cAMP
-
IC50: 1200 nM, PDE11A4
cGMP
-
IC50: 0.000075 mM, PDE3A; IC50: 0.00032 mM, PDE3B
cGMP
-
IC50: 560 nM, PDE11A4
cGMP
-
competitive inhibitor of PDE3A acting directly at the catalytic site
cGMP
-
the hydrolysis of cGMP by PDE3 inhibits the hydrolysis of cAMP
Chloropromazine
-
soluble but not particulate form
Cilostamide
-
50 mM, inhibits growth of acinar epithelial cells by 63%
Cilostamide
-
IC50: 0.000027 mM, PDE3A; IC50: 0.00005 mM, PDE3B; IC50: 0.0125 mM, PDE2
Cilostamide
-
IC50: 0.00013 mM, PDE3; IC50: 0.048 mM, PDE2; IC50: 0.221 mM, PDE1
cilostazol
-
IC50: 0.0002 mM, PDE3A; IC50: 0.00038 mM, PDE3B; IC50: 0.0452 mM, PDE2
cilostazol
-
-
cilostazol
-
a PDE3 inhibitor
Co2+
-
inhibits at concentrations higher than optimal
Co2+
-
inhibits at higher concentrations
Co2+
-
PdeA and PdeB are inhibited (20-30%) at 0.25 mM Co2+
daidzein
-
IC50: 0.0286 mM, PDE3
dibutyryl cyclic AMP
-
94% inhibition at 2.5 mM
dibutyryl cyclic AMP
-
-
dioclein
-
potent selective and calmodulin-independent inhibitor of PDE1, competitive inhibitor for cGMP hydrolysis by PDE1 in basal-activated (1 mM EGTA) and calmodulin-activated (18 nM calmodulin with 0.01 mM CaCl2) states. Dioclein is at least 11times more potent in inhibiting calmodulin-activated PDE1 than other PDE types. Among PDE1-PDE5, dioclein is at least 11fold more selective for the activated PDE1 isoform compared to basal PDE2 (70fold), activated PDE2 (26fold), PDE3 (19fold), PDE4 (11fold), and PDE5 (16fold)
dioclein
-
dioclein is at least 11times more potent in inhibiting calmodulin-activated PDE1 than other PDE types. Among PDE1-PDE5, dioclein is at least 11fold more selective for the activated PDE1 isoform compared to basal PDE2 (70fold), activated PDE2 (26fold)
dioclein
C7DXW3, C7DXW4, C7DXW5, C7DXW6, C7DXW7, -
-
diosmetin
-
IC50: 0.0048 mM, PDB2; IC50: 0.0144 mM, PDB1
dipyridamole
-
-
dipyridamole
-
50% inhibition at about 0.0002-0.00055 mM
dipyridamole
Q9HCR9
50% inhibition at 0.00082 mM; 50% inhibition at 0.0018 mM
dipyridamole
-
IC50: 0.00078 mM
dipyridamole
-
IC50: 0.0069 mM
dipyridamole
-
IC50: 840 nM, PDE11A4
dipyridamole
-
IC50: 0.00034 mM, PDE4A4
dipyridamole
-
inhibits with micromolar potency
E4021
-
50% inhibition at about 0.0005-0.001 mM
EDTA
-
complete loss of activity for mutants H23A, H169A, H207A
EDTA
-
PdeA and PdeB show 39% relative activity in the hydrolysis of 3',5'-cAMP in the presence of 0.05 mM EDTA
EHNA
-
a selective PDE2 inhibitor
eriodictyol
-
IC50: 0.0525 mM, PDB3
erythro-9-(2-hydroxy-3-nonyl)-adenine
-
IC50: 0.0092 mM, PDE2
erythro-9-(2-hydroxy-3-nonyl)adenine
-
50% inhibition at about 0.1 mM
erythro-9-(2-hydroxy-3-nonyl)adenine
-
IC50: 0.00061 mM for wild-type enzyme
erythro-9-(2-hydroxy-3-nonyl)adenine
Q01065
inhibition of isoform PDE2, results in increase in basal cGMP levels after application to thalamic neurons
etazolate
-
IC50: 0.0007 mM
ethylene glycobis(beta-aminoethyl ether)-N,N'-tetraacetic acid
-
soluble but not particulate form
-
Fe2+
-
strongly inhibitory at 2.5 mM
Fe2+
-
strong inhibition at 1 mM
Fe3+
-
strongly inhibitory at 2.5 mM
felodipine
-
-
genistein
-
IC50: 0.0017 mM, PDB2; IC50: 0.0129 mM, PDB3; IC50: 0.0168 mM, PDB1
IBMX
P27815
-
isobutylmethylxanthine
-
50% inhibition at about 0.05 mM
isobutylmethylxanthine
-
inhibits with micromolar potency
linoleic acid
-
-
luteolin
-
IC50: 0.0101 mM, PDB3; IC50: 0.0133 mM, PDB2; IC50: 0.0215 mM, PDB1
luteolin-7-glucoside
-
IC50: 0.0351 mM, PDB2
methylxanthines
-
-
-
Mg2+
-
inhibits at concentrations higher than optimal
Mg2+
-
inhibits at higher amounts
Milrinone
-
0.2627 mM, PDE1; IC50: 0.0001 mM, PDE3B; IC50: 0.00045 mM, PDE3A
Milrinone
-
50% inhibition at about 0.1 mM
Milrinone
P27815
-
Mn2+
-
inhibits at concentrations higher than optimal
myricetin
-
IC50: 0.0124 mM, PDB3; IC50: 0.0128 mM, PDB2; IC50: 0.0249 mM, PDB1
N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide
-
soluble but not particulate form
nicardipine
-
weak inhibitor
nicardipine
-
-
nimodipine
-
-
orthovanadate
-
PdeA shows 26% relative activity and PdeB shows 29% relative activity in the hydrolysis of 3',5'-cAMP in the presence of 0.05 mM orthovanadate
papaverine
-
-
papaverine
-
-
papaverine
-
IC50: 0.025 mM
papaverine
-
competitive inhibitor
papaverine
-
selective PDE10A inhibitor
phosphate
-
PdeA and PdeB enzyme activities are strongly inhibited by 0.1 M sodium phosphate buffer (pH 6.0 and 7.0), the PdeB activity is more strongly inhibited by 0.1 M phosphate than is PdeA activity
phosphoserine
-
PdeA shows 59% relative activity and PdeB shows 73% relative activity in the hydrolysis of 3',5'-cAMP in the presence of 0.05 mM phosphoserine
phosphotyrosine
-
PdeA shows 44% relative activity and PdeB shows 52% relative activity in the hydrolysis of 3',5'-cAMP in the presence of 0.05 mM phosphotyrosine
quercetin
-
IC50: 0.0056 mM, PDB3; IC50: 0.0179 mM, PDB2; IC50: 0.0278 mM, PDB1
quercetin-3,5,7,3',4'-O-pentaacetate
-
-
quercetin-3,5,7,3',4'-O-pentamethylether
-
-
quercetin-3,7,3',4'-O-tetramethylether
-
-
quercetin-3,7,4'-O-trimethylether
-
ayanin
quercetin-3-O-methyl-5,7,3',4'-O-tetraacetate
-
-
quercetin-3-O-methylether
-
-
quinazolinamine
-
IC50: 0.01 mM, PDE3; IC50: 0.23 mM, PDE1; IC50: 0.241 mM, PDE2
rolipram
Q01064
-
rolipram
-
weak inhibitor
rolipram
-
IC50: 0.15 mM for wild-type enzyme
RP-73401
-
IC50: 0.05 mM, PDE3; IC50: 0.067 mM, PDE2; IC50: 0.13 mM, PDE1
sarilesin
-
-
sildenafil
-
IC50: IC50: 0.00012 mM, PDE11; IC50: IC50: 0.0013 mM, PDE1
sildenafil
-
IC50: 1725 nM, PDE11; IC50: 350 nM, PDE1
sildenafil
-
IC50: 3800 nM, 1000fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
sildenafil
-
IC50: 0.00315 mM, PDE4A4
sildenafil
-
-
sildenafil
-
viagra, potent selective PDE5 inhibitor
SKF 94120
-
weak inhibitor
tadalafil
-
IC50: 67 nM, PDE11; IC50: above 10000 nM, PDE1
tadalafil
-
partially inhibits PDE11
tadalafil
-
PDE11 inhibition has impacts on sperm quality. Reasonable caution should by suggested in patients taking the prescribed dosages of tadalafil, a PDE5 inhibitor which could crossreact with human PDE11A splicing variants
tadalafil
-
IC50: 73 nM, 40fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
tadalafil
-
-
theophylline
-
-
trequinsin
-
IC50: 0.0039 mM
Trifluoperazine
-
-
vardenafil
-
IC50: 121 nM, PDE1; IC50: 308 nM, PDE11
vardenafil
-
IC50: 840 nM, 9300fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
vardenafil
-
-
vinpocetine
Q01064
-
vinpocetine
-
IC50: 0.0232 mM, PDE1
vinpocetine
-
50% inhibition at about 0.06-0.09 mM
vinpocetine
-
IC50: 0.0223
vinpocetine
-
comparison of inhibitory effect on several recombinant human PDE isoforms
vinpocetine
-
inhibitor of activated PDE1
zaprinast
Q01064
-
zaprinast
-
weak inhibitor
zaprinast
-
50% inhibition at about 0.016-0.02 mM
zaprinast
Q9HCR9
50% inhibition at 0.005 mM; 50% inhibition at 0.028 mM
zaprinast
-
IC50: 0.0016 mM, PDE11; IC50: 0.071 mM, PDE1
zaprinast
-
IC50: 0.00816 mM, PDE4A4
Zn2+
-
strongly inhibitory at 2.5 mM
Zn2+
-
PdeA and PdeB are potently inhibited in the hydrolysis of 3',5'-cAMP by 0.05 mM Zn2+ with 24% and 28% of remaining activity
Zn2+
-
strong inhibition at 1 mM
Mn2+
-
PdeA and PdeB are inhibited (20-30%) at 0.25 mM Mn2+
additional information
-
inhibition by monoclonal antibodies
-
additional information
-
-
-
additional information
-
-
-
additional information
-
not inhibitory: EDTA up to 2.5 mM
-
additional information
-
IC50 for vardenafil, sildenafil and tadalafil is above 10000 nM, PDE2
-
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 oxidant t-butylhydroperoxide signifcantly increases the cytosolic calcium concentration, which is prevented by inhibition of enzyme isoform PDE1. Inhibition of both isoforms PDE1 and PDE4 completely prevent the t-butylhydroperoxide stimulated TNF-alpha release
-
additional information
-
NAD+ is not an inhibitor of PDE3A
-
additional information
P27815
not inhibited by rolipram and sildenafil
-
additional information
-
PdeA and PdeB are not stimulated by 3-isobuthyl-1-methylxanthine, theophylline, beta-glycerophosphate, Ca2+, Mg2+, Fe2+, and Fe3+
-
additional information
-
the broad-spectrum phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, IBMX, has no effect on the activity of PdeE at 1 mM. No inhibition by theophylline at 1 mM, beta-glycerophosphate at 0.1 mM, and by orthovanadate
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
-
stimulates
ascorbic acid
-
stimulates
ascorbic acid
-
reduced, slight stimulation
Ca2+
-
isoform PDE1, stimulation of both hydrolysis of cAMP and cGMP
Calmodulin
-
differential effect on isozymes, activation only in complex with Ca2+, overview
Calmodulin
-
isoform PDE1, stimulation of both hydrolysis of cAMP and cGMP
cGMP
-
about 30fold stimulation of isoform PDE2A with EC50 value of 0.0011 mM
cGMP
-
PDE2 is stimulated by cGMP
cGMP
-
binding of cGMP to GAF domains within PDE2 results in the activation of all PDE2 variants
clozapine
-
chronic treatment with 20 mg/kg clozapine increases PDE10A expression by 62%
dithiothreitol
-
stimulates
dithiothreitol
P0A8Z7
or other reductant, required
EDTA
-
reverses Ca2+ inhibition
ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid
-
activation
ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid
-
reverses Ca2+ inhibition
glutathione
-
reduced, stimulates
glutathione
-
reduced, slight stimulation
haloperidol
-
chronic treatment with 1 mg/kg haloperidol increases PDE10A expression by 118%; chronic treatment with 1 mg/kg haloperidol increases PDE10A expression by 65%
imidazole
-
stimulates
lipopolysaccharide
-
expression and activity of isoforms PDE2, PDE3, PDE11 in cultured peritoneal macrophages are recovered after treatment of cultured cells with lipopolysaccharide. Lipopolysaccharide also up-regulates enzyme expression in resident peritoneal macrophages
lysophosphatidylcholine
-
stimulation
phosphatidylinositol
-
stimulation
stearate
-
stimulation
Subtilisin
-
stimulation, slightly more effective than trypsin
-
Trypsin
-
activation
-
lysophosphatidylethanolamine
-
stimulation
additional information
-
not influenced by treatment with clozapine
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0038
-
2',3'-cAMP
-
PdeA, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.0052
-
2',3'-cAMP
-
PdeB, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.000079
-
3',5'-cAMP
-
isoform PDE3A-94
0.000088
-
3',5'-cAMP
-
isoform PDE3A-136
0.000093
-
3',5'-cAMP
-
isoform PDE3A-118
0.000094
-
3',5'-cAMP
-
30C, pH 8.0, PDE3A
0.0001
-
3',5'-cAMP
-
-
0.00018
-
3',5'-cAMP
-
-
0.0002
-
3',5'-cAMP
-
-
0.00024
-
3',5'-cAMP
-
30C, pH 8.0, PDE3A
0.00029
-
3',5'-cAMP
-
30C, pH 8.0, PDE3B
0.00047
-
3',5'-cAMP
-
30C, pH 8.0, PDE3B
0.0009
-
3',5'-cAMP
-
-
0.0018
-
3',5'-cAMP
-
-
0.0024
-
3',5'-cAMP
-
30C, pH 7.5, PDE11A4
0.0033
-
3',5'-cAMP
-
PdeA, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.005
-
3',5'-cAMP
-
PdeB, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.0075
-
3',5'-cAMP
-
two forms of phosphodiesterase
0.0185
-
3',5'-cAMP
-
PDE11
0.0205
-
3',5'-cAMP
-
PDE1
0.03
-
3',5'-cAMP
-
-
0.0316
-
3',5'-cAMP
-
-
0.032
-
3',5'-cAMP
-
catalytic domain of PDE2A (PDE2A residues 578-919), enzyme expressed in Escherichia coli
0.033
-
3',5'-cAMP
-
-
0.0464
-
3',5'-cAMP
-
30C, pH 8.0, PDE2
0.09
-
3',5'-cAMP
-
particulate enzyme
0.095
-
3',5'-cAMP
-
two forms of phosphodiesterase
0.125
-
3',5'-cAMP
-
soluble enzyme
7
-
3',5'-cAMP
-
-
0.00002
-
3',5'-cGMP
-
-
0.0001
-
3',5'-cGMP
-
-
0.00097
-
3',5'-cGMP
-
30C, pH 7.5, PDE11A4
0.002
-
3',5'-cGMP
-
-
0.0023
-
3',5'-cGMP
-
-
0.005
-
3',5'-cGMP
-
-
0.006
-
3',5'-cGMP
-
PDE11
0.0088
-
3',5'-cGMP
-
-
0.015
-
3',5'-cGMP
-
-
0.0153
-
3',5'-cGMP
-
PDE1
0.03
-
3',5'-cGMP
-
soluble enzyme
0.034
-
3',5'-cGMP
-
catalytic domain of PDE2A (PDE2A residues 578-919), enzyme expressed in Escherichia coli
0.0464
-
3',5'-cGMP
-
30C, pH 8.0, PDE1
0.0782
-
3',5'-cGMP
-
-
0.1
-
3',5'-cGMP
-
particulate enzyme
0.0014
-
5'-AMP
-
PdeB, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.0016
-
5'-AMP
-
PdeA, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.0033
-
5'-ATP
-
PdeB, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.0125
-
5'-ATP
-
PdeA, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.012
-
adenosine 3',5'-cyclic phosphate
-
pH 7.0, 55C
0.00023
-
cAMP
-
pH 7.5, 30C
0.00075
-
cAMP
-
isoform PDE1, 22C, pH 7.0
0.0017
-
cAMP
-
isoform PDE1C, pH 7.4
0.002
0.004
cAMP
-
-
0.0033
-
cAMP
Q9HCR9
pH 7.5
0.005
-
cAMP
-
isoform PDE2, 22C, pH 7.0
0.0057
-
cAMP
Q9HCR9
pH 7.5
0.012
-
cAMP
-
brain 63 kDA isozyme
0.0125
-
cAMP
-
isoform PDE7, 22C, pH 7.0
0.035
-
cAMP
-
brain 60 kDA isozyme
0.04
-
cAMP
-
heart isozyme
0.042
-
cAMP
-
lung isozyme
0.45
-
cAMP
-
isoform PDE11A1; isoform PDE11A2
0.8
-
cAMP
-
isoform PDE11A3
1.6
-
cAMP
-
isoform PDE11A4
0.0002
-
cGMP
-
isoform PDE3, 22C, pH 7.0
0.0012
-
cGMP
-
brain 63 kDA isozyme
0.0013
0.0016
cGMP
-
-
0.0013
-
cGMP
-
isoform PDE1C, pH 7.4
0.0027
-
cGMP
-
brain 60 kDA isozyme
0.0028
-
cGMP
-
lung isozyme
0.0032
-
cGMP
-
heart isozyme
0.0037
-
cGMP
Q9HCR9
pH 7.5
0.0042
-
cGMP
Q9HCR9
pH 7.5
0.34
-
cGMP
-
isoform PDE11A2
0.4
-
cGMP
-
isoform PDE11A1
0.8
-
cGMP
-
isoform PDE11A3
1
-
cGMP
-
isoform PDE11A4
0.025
-
guanosine 3',5'-cyclic phosphate
-
pH 7.0, 55C
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
three isoenzymes
-
additional information
-
additional information
-
biphasic behaviour with 3',5'-cAMP as substrate
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0006
-
2',3'-cAMP
-
PdeB, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.00096
-
2',3'-cAMP
-
PdeA, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.00093
-
3',5'-cAMP
-
PdeB, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.00096
-
3',5'-cAMP
-
PdeA, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.3
-
3',5'-cAMP
-
catalytic domain of PDE2A (PDE2A residues 578-919), enzyme expressed in Escherichia coli
0.48
-
3',5'-cAMP
-
isoform PDE3A-136
0.5
-
3',5'-cAMP
-
isoform PDE3A-118
0.52
-
3',5'-cAMP
-
isoform PDE3A-94
4.2
-
3',5'-cGMP
-
catalytic domain of PDE2A (PDE2A residues 578-919), enzyme expressed in Escherichia coli
0.0031
-
5'-AMP
-
PdeB, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.00551
-
5'-AMP
-
PdeA, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.00155
-
5'-ATP
-
PdeB, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.00454
-
5'-ATP
-
PdeA, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
567
-
cAMP
-
stimulation with Mg2+ or Mn2+
667
-
cGMP
-
stimulation with Mg2+ or Mn2+
additional information
-
additional information
-
-
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.000062
-
(-)-6-(3-(3-cyclopropyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
-
0.0434
-
(Rp)-guanosine-3',5'-cyclic-S-(4-bromo-2,3-dioxobutyl)monophosphorothioate
-
in 45 mM HEPES (pH 7.2), 20 mM MgCl2, and 4 mM MES, at 25C
0.0000003
-
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
-
-
0.00002
-
3',5'-cGMP
-
isoform PDE3A-118
0.000028
-
3',5'-cGMP
-
isoform PDE3A-94
0.00003
-
3',5'-cGMP
-
isoform PDE3A-136
0.0003
-
5-(2-propoxyphenyl)-2,3-dihydro-7H-[1,2,3]triazolo[4,5-d]pyrimidin-7-one
-
-
0.00000022
-
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
-
0.000039
-
cilostazol
-
isoform PDE3A-118
0.00005
-
cilostazol
-
isoform PDE3A-136
0.000056
-
cilostazol
-
isoform PDE3A-94
0.00055
-
dioclein
-
isoform PDE1 in basal-activated state, pH and temperature not specified in the publication
0.00062
-
dioclein
-
isoform PDE1 in calmodulin-activated state, pH and temperature not specified in the publication
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0001
-
(-)-6-(3-(3-cyclopropyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.0001 mM, PDE3A
0.00028
-
(-)-6-(3-(3-cyclopropyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.00028 mM, PDE3B
0.0043
-
(2R,3R)-3-(6-amino-9H-purin-9-yl)nonan-2-ol
-
IC50: 0.0043 mM, PDE2
0.0023
-
(2S,3R)-3-(7-amino-3H-imidazo[4,5-b]pyridin-3-yl)nonan-2-ol
-
isoform PDE2, pH and temperature not specified in the publication
0.000006
-
(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: 0.000006 mM, PDE3
0.0012
-
(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: 0.0012 mM, PDE2
0.015
-
(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: 0.015 mM, PDE1
0.052
-
1-(2-methylbenzyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.053
-
1-(2-methylbenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.0097
-
1-(3-chlorobenzyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.0095
-
1-(3-chlorobenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.016
-
1-(3-methylbenzyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.0023
-
1-(4-chlorobenzyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.0007
-
1-(4-chlorobenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.0014
-
1-(4-methylbenzyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.0015
-
1-(4-methylbenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.028
-
1-benzyl-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.00000034
-
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
-
IC50: 0.00000034 mM, PDE3A, highly selective PDE3 inhibitor
0.0000019
-
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
-
IC50: 0.0000019 mM, PDE3B
0.0209
-
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
-
IC50: 0.0.0209 mM, PDE2
0.1129
-
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
-
IC50: 0.1129 mM, PDE1
0.000001
-
2-[[4-[4-pyridin-4-yl-1-(2,2, 2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline succinic acid
-
the IC50 of the compound for inhibition of PDE10A in vitro is less than 1 nM
-
0.02654
-
3-isobutyl-1-methyl-1H-purine-2,6(3H,7H)-dione
-
IC50: 0.02654 mM, PDE4A4
0.0402
-
3-isobutyl-1-methyl-1H-purine-2,6(3H,7H)-dione
-
IC50: 0.0402 mM
0.068
-
3-isobutyl-1-methyl-1H-purine-2,6(3H,7H)-dione
-
IC50: 0.068 mM
0.00000032
-
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.00000032 mM, PDE3A, highly selective PDE3 inhibitor
0.0000015
-
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.0000015 mM, PDE3B
0.0429
-
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.0429 mM, PDE1
0.0523
-
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.0523 mM, PDE2
0.0152
-
8-methoxymethyl-isobutylmethylxanthine
-
isoform PDE1 in basal-activated state, pH and temperature not specified in the publication
0.0167
-
amrinone
-
IC50: 0.0167 mM, PDE3A
0.0312
-
amrinone
-
IC50: 0.0312 mM, PDE3B
0.0105
-
apigenin
-
IC50: 0.0105 mM, PDB3
0.0167
-
apigenin
-
IC50: 0.0167 mM, PDB2
0.0254
-
apigenin
-
IC50: 0.0254 mM, PDB1
0.0279
-
Biochanin A
-
IC50: 0.0279 mM, PDE2
0.0291
-
Biochanin A
-
IC50: 0.0291 mM, PDE1
0.0012
-
cAMP
-
IC50: 1200 nM, PDE11A4
0.000059
-
cGMP
-
isoform PDE3A
0.000075
-
cGMP
-
IC50: 0.000075 mM, PDE3A
0.00032
-
cGMP
-
IC50: 0.00032 mM, PDE3B
0.00056
-
cGMP
-
IC50: 560 nM, PDE11A4
0.000027
-
Cilostamide
-
IC50: 0.000027 mM, PDE3A
0.00005
-
Cilostamide
-
IC50: 0.00005 mM, PDE3B
0.00013
-
Cilostamide
-
IC50: 0.00013 mM, PDE3
0.00037
-
Cilostamide
P27815
-
0.0125
-
Cilostamide
-
IC50: 0.0125 mM, PDE2
0.048
-
Cilostamide
-
IC50: 0.048 mM, PDE2
0.221
-
Cilostamide
-
IC50: 0.221 mM, PDE1
0.0002
-
cilostazol
-
IC50: 0.0002 mM, PDE3A
0.00038
-
cilostazol
-
IC50: 0.00038 mM, PDE3B
0.0452
-
cilostazol
-
IC50: 0.0452 mM, PDE2
0.0286
-
daidzein
-
IC50: 0.0286 mM, PDE3
0.00144
-
dioclein
-
isoform PDE1 in basal-activated state, pH and temperature not specified in the publication
0.00247
-
dioclein
-
isoform PDE1 in calmodulin-activated state, pH and temperature not specified in the publication
0.0382
-
dioclein
-
isoform PDE2 in calmodulin-activated state, pH and temperature not specified in the publication
0.1
-
dioclein
-
isoform PDE2 in basal-activated state, pH and temperature not specified in the publication
0.0048
-
diosmetin
-
IC50: 0.0048 mM, PDB2
0.0144
-
diosmetin
-
IC50: 0.0144 mM, PDB1
0.00034
-
dipyridamole
-
IC50: 0.00034 mM, PDE4A4
0.00078
-
dipyridamole
-
IC50: 0.00078 mM
0.00084
-
dipyridamole
-
IC50: 840 nM, PDE11A4
0.0069
-
dipyridamole
-
IC50: 0.0069 mM
0.0525
-
eriodictyol
-
IC50: 0.0525 mM, PDB3
0.0092
-
erythro-9-(2-hydroxy-3-nonyl)-adenine
-
IC50: 0.0092 mM, PDE2
0.00061
-
erythro-9-(2-hydroxy-3-nonyl)adenine
-
IC50: 0.00061 mM for wild-type enzyme
0.0007
-
etazolate
-
IC50: 0.0007 mM
0.0017
-
genistein
-
IC50: 0.0017 mM, PDB2
0.0129
-
genistein
-
IC50: 0.0129 mM, PDB3
0.0168
-
genistein
-
IC50: 0.0168 mM, PDB1
0.0043
-
IBMX
-
-
0.0127
-
IBMX
P27815
-
0.0101
-
luteolin
-
IC50: 0.0101 mM, PDB3
0.0133
-
luteolin
-
IC50: 0.0133 mM, PDB2
0.0215
-
luteolin
-
IC50: 0.0215 mM, PDB1
0.0351
-
luteolin-7-glucoside
-
IC50: 0.0351 mM, PDB2
0.0001
-
Milrinone
-
IC50: 0.0001 mM, PDE3B
0.00045
-
Milrinone
-
IC50: 0.00045 mM, PDE3A
0.002
-
Milrinone
-
PDE3
0.0124
-
myricetin
-
IC50: 0.0124 mM, PDB3
0.0128
-
myricetin
-
IC50: 0.0128 mM, PDB2
0.0249
-
myricetin
-
IC50: 0.0249 mM, PDB1
0.0032
-
nimodipine
-
isoform PDE1, pH and temperature not specified in the publication
0.000036
-
papaverine
-
-
0.025
-
papaverine
-
IC50: 0.025 mM
0.0056
-
quercetin
-
IC50: 0.0056 mM, PDB3
0.0056
-
quercetin
-
PDE3
0.0179
-
quercetin
-
IC50: 0.0179 mM, PDB2
0.0278
-
quercetin
-
IC50: 0.0278 mM, PDB1
0.002
-
quercetin-3,5,7,3',4'-O-pentaacetate
-
PDE3
0.0047
-
quercetin-3,5,7,3',4'-O-pentamethylether
-
PDE3
0.0228
-
quercetin-3,7,3',4'-O-tetramethylether
-
PDE3
0.0041
-
quercetin-3,7,4'-O-trimethylether
-
PDE3
0.0008
-
quercetin-3-O-methyl-5,7,3',4'-O-tetraacetate
-
PDE3
0.0016
-
quercetin-3-O-methylether
-
PDE3
0.0869
-
quercetin-3-O-methylether
-
PDE3
0.01
-
quinazolinamine
-
IC50: 0.01 mM, PDE3
0.23
-
quinazolinamine
-
IC50: 0.23 mM, PDE1
0.241
-
quinazolinamine
-
IC50: 0.241 mM, PDE2
0.15
-
rolipram
-
IC50: 0.15 mM for wild-type enzyme
0.05
-
RP-73401
-
IC50: 0.05 mM, PDE3
0.067
-
RP-73401
-
IC50: 0.067 mM, PDE2
0.13
-
RP-73401
-
IC50: 0.13 mM, PDE1
0.00012
-
sildenafil
-
IC50: 0.00012 mM, PDE11
0.00035
-
sildenafil
-
IC50: 350 nM, PDE1
0.0013
-
sildenafil
-
IC50: 0.0013 mM, PDE1
0.001725
-
sildenafil
-
IC50: 1725 nM, PDE11
0.00315
-
sildenafil
-
IC50: 0.00315 mM, PDE4A4
0.0038
-
sildenafil
-
IC50: 3800 nM, 1000fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
0.000015
-
tadalafil
-
isoform PDE11A1
0.000019
-
tadalafil
-
isoform PDE11A3
0.000021
-
tadalafil
-
isoform PDE11A2
0.000067
-
tadalafil
-
IC50: 67 nM, PDE11
0.000073
-
tadalafil
-
IC50: 73 nM, 40fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
0.000073
-
tadalafil
-
isoform PDE11A4
0.01
-
tadalafil
-
IC50: above 10000 nM, PDE1
0.0039
-
trequinsin
-
IC50: 0.0039 mM
0.000121
-
vardenafil
-
IC50: 121 nM, PDE1
0.000151
-
vardenafil
-
isoform PDE11A3
0.000163
-
vardenafil
-
isoform PDE11A1
0.000166
-
vardenafil
-
isoform PDE11A2
0.000308
-
vardenafil
-
IC50: 308 nM, PDE11
0.00065
-
vardenafil
-
isoform PDE11A4
0.00084
-
vardenafil
-
IC50: 840 nM, 9300fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
0.0223
-
vinpocetine
-
IC50: 0.0223 mM
0.0232
-
vinpocetine
-
IC50: 0.0232 mM, PDE1
0.185
-
vinpocetine
-
isoform PDE1 in basal-activated state, pH and temperature not specified in the publication
0.0016
-
zaprinast
-
IC50: 0.0016 mM, PDE11
0.00816
-
zaprinast
-
IC50: 0.00816 mM, PDE4A4
0.071
-
zaprinast
-
IC50: 0.071 mM, PDE1
0.007
-
Milrinone
P27815
-
0.01
-
additional information
-
IC50 for vardenafil, sildenafil and tadalafil is above 10000 nM, PDE2
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0207
-
-
substrate cGMP, pH 7.0, 55C
0.0309
-
-
substrate cAMP, pH 7.0, 55C
0.36
-
-
-
1.33
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
kinetic properties, overview
additional information
-
-
description of a technique used to estimate the extent of PDE1 activation in vivo by measuring in vitro the PDE activity
additional information
-
-
assay procedure of calmodulin-dependent cyclic nucleotide phosphodiesterase
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
-
-
assay at
7.5
8.5
-
for 3',5'-cAMP with 0.1 M Tris-HCl buffer
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
9
-
PdeB shows no 3',5'-cAMP phosphodiesterase activity at or below pH 6
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
40
-
-
the optimum temperature for the 3',5'-cAMP phosphodiesterase activity of PdeA is 40C
50
-
-
the optimum temperature for the 3',5'-cAMP phosphodiesterase activity of PdeA is 50C
55
-
-
assay at
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.9
-
-
calculated from sequence
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
glioblastoma cell, expression of isoform PDE1C and lower levels of isoforms PDE2, PDE3, PDE4, and PDE5
Manually annotated by BRENDA team
-
lung epithelial cell
Manually annotated by BRENDA team
-
epithelial and endothelial cells
Manually annotated by BRENDA team
Q13370, Q14123, Q14432, Q9HCR9, Q9Y233
-
Manually annotated by BRENDA team
-
PDE1; PDE10; PDE11; PDE2; PDE3
Manually annotated by BRENDA team
-
PDE 1 vascular expression is increased in arteries from angiotensin II hypertensive rats
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
PDE 1 vascular expression is increased in arteries from angiotensin II hypertensive rats
-
Manually annotated by BRENDA team
Q13370, Q14123, Q14432, Q9HCR9, Q9Y233
-
Manually annotated by BRENDA team
-
fetal and adult
Manually annotated by BRENDA team
-
striatum and olfactory tubercle
Manually annotated by BRENDA team
-
highest enzymic activity
Manually annotated by BRENDA team
-
PDE1; PDE2
Manually annotated by BRENDA team
-
PDE10A is strongly expressed in the brain, highly expressed in striatal complex including caudate putamen, nucleus accumbens, and olfacory tubercle
Manually annotated by BRENDA team
Q13370, Q14123, Q14432, Q9HCR9, Q9Y233
parietal, frontal, temporal cortex, hippocampus, striatum, thalamus, hypothalamus, substantia nigra, nucleus accumbens, cerebellum; parietal, frontal, temporal cortex, hippocampus, striatum, thalamus, hypothalamus, substantia nigra, nucleus accumbens, cerebellum; parietal, frontal, temporal cortex, hippocampus, striatum, thalamus, hypothalamus, substantia nigra, nucleus accumbens, cerebellum; parietal, frontal, temporal cortex, hippocampus, striatum, thalamus, hypothalamus, substantia nigra, nucleus accumbens, cerebellum; parietal, frontal, temporal cortex, hippocampus, striatum, thalamus, hypothalamus, substantia nigra, nucleus accumbens, cerebellum; parietal, frontal, temporal cortex, hippocampus, striatum, thalamus, hypothalamus, substantia nigra, nucleus accumbens, cerebellum; parietal, frontal, temporal cortex, hippocampus, striatum, thalamus, hypothalamus, substantia nigra, nucleus accumbens, cerebellum; parietal, frontal, temporal cortex, hippocampus, striatum, thalamus, hypothalamus, substantia nigra, nucleus accumbens, cerebellum
Manually annotated by BRENDA team
-
activity is one-tenth compared to normal tissue
Manually annotated by BRENDA team
-
phosphodiesterase 3 is exclusively detected in smooth muscle cells of the wall, no activity in vascular endothelial layer
Manually annotated by BRENDA team
-
external layer of
Manually annotated by BRENDA team
-
predominant expression of isoform PDE1A
Manually annotated by BRENDA team
C7DXW3, C7DXW4, C7DXW5, C7DXW6, C7DXW7, -
-
Manually annotated by BRENDA team
-
epithelial cells and macrophages
Manually annotated by BRENDA team
-
PDE10A is highly expressed in the medium spiny neurons of the striatum
Manually annotated by BRENDA team
-
expression of isoform PDE3 in clitoral epidermis
Manually annotated by BRENDA team
-
fetal and adult
Manually annotated by BRENDA team
-
10-20% of activity found in brain
Manually annotated by BRENDA team
-
PDE1; PDE2
Manually annotated by BRENDA team
-
PDE11A4, weak antibody staining of neuronal cells within parasympathetic ganglia in the heart
Manually annotated by BRENDA team
Q13370, Q14123, Q14432, Q9HCR9, Q9Y233
-
Manually annotated by BRENDA team
Q13370, Q14123, Q14432, Q9HCR9, Q9Y233
-
Manually annotated by BRENDA team
Q13370, Q14123, Q14432, Q9HCR9, Q9Y233
-
Manually annotated by BRENDA team
-
macrophage cell
Manually annotated by BRENDA team
-
fetal and adult
Manually annotated by BRENDA team
-
tubule epithelial cells
Manually annotated by BRENDA team
Q13370, Q14123, Q14432, Q9HCR9, Q9Y233
-
Manually annotated by BRENDA team
-
trachea submucosal gland
Manually annotated by BRENDA team
-
myometrial cell, level of isoform PDE1C decreases in all conditions that inhibit proliferation
Manually annotated by BRENDA team
-
olfactory sensory
Manually annotated by BRENDA team
Q01065
living thalamic neurons, expression of enzyme isoforms PDE1, PDE2, PDE9, and PDE10
Manually annotated by BRENDA team
-
PDE10A is highly expressed in striatal medium-sized spiny projection neurons
Manually annotated by BRENDA team
-
cultured, PDE1; cultured, PDE3
Manually annotated by BRENDA team
Q13370, Q14123, Q14432, Q9HCR9, Q9Y233
-
Manually annotated by BRENDA team
-
in freshly isolated peritoneal exudate macrophage, isoforms PDE1, PDE2, PDE3, PDE10, PDE11 are expressed. After 24h of cultures, levels of isoforms PDE2, PDE3, and PDE11 are markedly decreased. Their expression and activity are recovered after treatment of cultured cells with lipopolysaccharide
Manually annotated by BRENDA team
-
main distribution in glandular and subglandular areas
Manually annotated by BRENDA team
-
PDE11A4, strong antibody staining in the glandular epithelium
Manually annotated by BRENDA team
-
PDE11A2; PDE11A4
Manually annotated by BRENDA team
-
epithelial, endothelial and smooth muscle cells
Manually annotated by BRENDA team
-
PDE1 is expressed in only a subset of the Purkinje cells
Manually annotated by BRENDA team
-
splice variant PDE1A is distributed in outer retina, especially in the outer segments of photoreceptors. Variant PDE1B is uniformly distributed across the retina, PDE1C is confined mainly to the inner retina with precise localization to the inner nuclear layer
Manually annotated by BRENDA team
-
PDE11A1 is predominantly present in; PDE11A2
Manually annotated by BRENDA team
Q13370, Q14123, Q14432, Q9HCR9, Q9Y233
-
Manually annotated by BRENDA team
Q13370, Q14123, Q14432, Q9HCR9, Q9Y233
-
Manually annotated by BRENDA team
-
of central cavernous arteries
Manually annotated by BRENDA team
Q61481
PDE1A_v7 is the major form of cyclic nucleotide phosphodiesterase 1A expressed in mature sperm
Manually annotated by BRENDA team
Q01062
cervical spinal cord, expression of isoforms PDE2, PDE5, and PDE9 in all lamina, in ventral motor neurons and in ependymal cells lining the central canal. Study on the influence of enzyme activity on NO-stimulated cGMP levels
Manually annotated by BRENDA team
Q13370, Q14123, Q14432, Q9HCR9, Q9Y233
-
Manually annotated by BRENDA team
Q13370, Q14123, Q14432, Q9HCR9, Q9Y233
-
Manually annotated by BRENDA team
-
acinar epithelial cell
Manually annotated by BRENDA team
-
PDE1 is present in young and adult gland; PDE2 is present in young gland, not in adult; PDE3 is present in young and adult gland
Manually annotated by BRENDA team
-
PDE1; PDE2; PDE3
Manually annotated by BRENDA team
-
PDE11A2; PDE11A3
Manually annotated by BRENDA team
-
Leydig cells and spermatogenic cells
Manually annotated by BRENDA team
Q01065
living thalamic neurons, expression of enzyme isoforms PDE1, PDE2, PDE9, and PDE10
Manually annotated by BRENDA team
Q13370, Q14123, Q14432, Q9HCR9, Q9Y233
-
Manually annotated by BRENDA team
-
enzyme isoform PDE1A is predominantly cytoplasmic in medial contractile vascular smoth muscle cell and nuclear in neointimal synthetic vascular smoth muscle cell
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
real-time monitoring of PDE2 activity by a fluorescent cAMP sensor shows that activation of PDE2 results in a rapid decrease of intracellular cAMP from high micromolar to sub-micromolar range within a few seconds
Manually annotated by BRENDA team
Q13370, Q14123, Q14432, Q9HCR9, Q9Y233
-
Manually annotated by BRENDA team
additional information
-
-
Manually annotated by BRENDA team
additional information
-
no activity of PDE3 in A5 epithelial duct cells
Manually annotated by BRENDA team
additional information
-
tissue-specific expression of splice-variants
Manually annotated by BRENDA team
additional information
-
no PDE3 activity is detected in SAOS-2 cells
Manually annotated by BRENDA team
additional information
-
no PDE11A protein is detected in blood vessels, cardiac myocytes, skeletal muscle, testis or penis
Manually annotated by BRENDA team
additional information
Q13370, Q14123, Q14432, Q9HCR9, Q9Y233
determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview; determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview; determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview; determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview; determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview; determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview; determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview; determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
PDE3B is associated with caveola in primary adipocytes
Manually annotated by BRENDA team
-
isoforms PDE1, PDE2,PDE3, PDE10, PDE11
Manually annotated by BRENDA team
-
enzyme isoform PDE1A is predominantly cytoplasmic in medial contractile vascular smoth muscle cell and nuclear in neointimal synthetic vascular smoth muscle cell. Cytoplasmic isoform PDE1A regulates myosin light chain phosphorylation with little effect on apoptosis
Manually annotated by BRENDA team
-
PDE1B is found almost exclusively in the cytosolic fraction
Manually annotated by BRENDA team
-
isoforms PDE2,PDE3, PDE10, PDE11
Manually annotated by BRENDA team
-
PDE10A is found almost exclusively in the membrane fraction
Manually annotated by BRENDA team
-
PDE4 (56%) and PDE3 (44%) are the main cyclic phosphodiesterase activities in cardiac nuclei
Manually annotated by BRENDA team
-
enzyme isoform PDE1A is predominantly cytoplasmic in medial contractile vascular smoth muscle cell and nuclear in neointimal synthetic vascular smoth muscle cell. Nuclear enzyme isoform PDE1A is important in vascular smoth muscle cell growth and survival
Manually annotated by BRENDA team
-
about 90% of total activity
-
Manually annotated by BRENDA team
-
PDE2A2 and PDE2A3, and PDE3A and PDE3B
Manually annotated by BRENDA team
additional information
-
spatial and temporal expression profiles of PDE1A, PDE1B, PDE1C and their physiological roles
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
29000
-
-
PdeA, SDS-PAGE
34000
-
-
PdeB, SDS-PAGE
41000
-
-
SDS-PAGE
42500
-
-
gel filtration, a third form of cyclic nucleotide phosphodiesterase
44500
-
-
gel filtration
57000
-
-
gel filtration
59000
-
-
SDS-PAGE
60000
-
-
SDS-PAGE
66000
-
-
SDS-PAGE
74000
-
-
SDS-PAGE
82000
-
-
Rhizobium fredii MAR-1, gel filtration
83000
-
-
gel filtration in presence of EGTA, monomer
102000
-
-
SDS-PAGE
110000
-
-
isoform PDE11A2, gel filtration
112000
124000
-
equilibrium sedimentation
116000
124000
-
sedimentation data
124000
-
-
-
140000
-
-
gel filtration
140000
-
-
gel filtration
140000
-
-
isoform PDE11A3, gel filtration
150000
-
-
gel filtration
151000
-
-
gel filtration in presence of EGTA, dimer
190000
-
-
isoform PDE11A4, gel filtration
201000
-
-
sedimentation coefficient, Stokes radius
220000
-
-
isoform PDE11A1, gel filtration
330000
400000
-
gel filtration in presence of EGTA, tetramer
additional information
-
-
-
additional information
-
-
-
additional information
-
-
overview
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
Q9HCR9
x * 65800, deduced from gene sequence; x * 78100, deduced from gene sequence
?
-
x * 103169, calculated from sequence
?
-
x * 72000, splice variant PDE1C1, x * 75000, splice variant PDE1C3
?
-
x * 63000, splice variant PDE1B, x * 74000 and x * 70000, splice variant PDE1C, x * 79000, splice variant PDE1A
?
-
x * 27600, about, sequence calculation
dimer
-
2 * 61000; SDS-PAGE
dimer
-
1 * 60000 + 1 * 63000, heterodimeric or homodimeric, SDS-PAGE
dimer
-
2 * 59000, SDS-PAGE
dimer
-
-
dimer
-
2 * 68000, SDS-PAGE
dimer
-
2 * 60000, SDS-PAGE, brain PDE1 isoform
dimer
-
2 * 21000, SDS-PAGE
dimer
-
2 * 60000
dimer
-
2 * 105000, calculated, 2 * 100000, SDS-PAGE of PDE11A4, 2 * 78000, calculated, 2 * 75000, SDS-PAGE of PDE11A3, 2 * 66000, calculated, 2 * 64000, SDS-PAGE of PDE11A2, 2 * 56000, calculated, 2 * 55000, SDS-PAGE ofPDE11A1
dimer
O06629
crystallization data
dimer
Sinorhizobium fredii MAR-1
-
2 * 21000, SDS-PAGE
-
monomer
-
1 * 41000, SDS-PAGE
monomer
-
1 * 66000, SDS-PAGE
oligomer
-
SDS-PAGE; x * 28000
oligomer
-
SDS-PAGE; x * 66000
oligomer
-
x * 63000, bovine brain, x * 60000, bovine heart, lung and brain, SDS-PAGE
monomer
-
1 * 59000, SDS-PAGE
additional information
-
PDE1 exists as tissue-specific and immunological distinct isozymes, overview
additional information
-
overview on subunit composition and partial amino acid sequences
additional information
-
nuclear and cytoplasmic enzyme isoform PDE1A are associated with contractile marker SM-calponin and growth marker Ki-67, respectively
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
-
regulation by phosphorylation, overview
phosphoprotein
-
in adipocytes, insulin induces formation of macromolecular complexes containing signaling molecules such as IRS-1, PI3K and PKB, proteins involved in PDE3B activation/phosphorylation
phosphoprotein
-
60 kDa PDE1, substrate of cAMP-dependent protein kinase, 63 kDa PDE1, substrate of calmodulin-dependent protein kinase, reversion for both by calcineurin, overview on regulation by phosphorylation
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
vapor diffusion method, crystal structure of the catalytic domain of PDE2A (PDE2A residues 578-919) determined at 1.7 A resolution
-
enzyme is a Fe3+-Mn2+-binuclear dimer, and the metal ions contribute to dimerization. Wild-type has a molecule of phosphate bound in the active site. Structure of mutants N97A lacking one of the Mn2+ coordinating residues and D66A that has a compromised cAMP hydrolytic activity
O06629
homology modeling of enzyme, based on kidny bean PAP and Mre nuclease
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
28
-
-
80% of activity remaining after 7 days
28
-
-
80% of activity remains for at least 10 days
60
-
-
20 min, no loss of activity
60
-
-
third form of cyclic nucleotide phosphodiesterase looses all its activity after 20 min
70
-
-
20 min, 20% loss of activity
95
-
-
stable up to
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
50% glycerol stabilizes
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-70C, 15% glycerol, 5 mg/ml ovalbumin, stable for at least 4 months
-
0C, EGTA, rapid loss of activity, inactivation retarded by bovine serum albumin, stability of Ca2+-dependent enzyme
-
4-7C, 40% glycerol, 0.00015 mM NaCl, stable for at least 1 year
-
repeated freezing and thawing, loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
13900fold
-
3700fold
-
6fold
-
anion exchange chromatography
-
overview
-
partially purified by Q-Sepharose column chromatography
-
2500-3000fold
-
anion exchange chromatography
-
nickel resin column chromatography
-
5000fold
-
overview
-
540fold
-
Talon column chromatography
-
immunoaffinity chromatography
-
2000fold
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
baculovirus-expressed PDE1 in Sf9 cells; baculovirus-expressed PDE2 in Sf9 cells; baculovirus-expressed PDE3A in Sf9 cells; baculovirus-expressed PDE3B in Sf9 cells
-
expression in Drosophila S2 cells, PDE1; expression in Drosophila S2 cells, PDE11
-
baculovirus expression system, PDE11A4
-
Epac1-camps-PDE3A fusion protein is expressed in HEK-293 cells
P27815
expressed in a baculovirus/insect cell Sf9 system
-
expression by using a baculovirus expression system
-
expression in COS-7 cells
-
expression in insect cells or in Escherichia coli
-
expression in NIH3006 murine fibroblasts and baculovirus-infected Sf9 insect cells
-
expression in Saccharomyces cerevisiae
Q01064
PDE3A expression in HEK-293 cells on the plasma membrane
-
-
Q61481
expression in Escherichia coli and in Mycobacterium leprae; overexpression in Mycobacterium smegmatis and Escherichia coli
-
expressed in Escherichia coli pG-Tf2/BL21 cells
-
gene pdeE, sequence comparisons
-
expressed in COS-1 cells
-
expression in NIH3006 murine fibroblasts and Sf9 insect cells
-
expression in Saccharomyces cerevisiae
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
epinephrine infusion stimulates skeletal muscle PDE2A expression
-
angiotensin II is able to increase PDE1 expression in vascular smooth muscle cells
-
angiotensin II is able to increase PDE1 expression in vascular smooth muscle cells
Rattus norvegicus Sprague-Dawley
-
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
D106A
-
mutation does not influence h-prune phosphodiesterase activity
D811A
-
activity towards 3',5'-cGMP is similar to wild-type activity, activity towards 3',5'-cAMP is less than 50% of wild-type activity. Increase in IC50-value for erythro-9-(2-hydroxy-3-nonyl)adenine, decrease in IC50-value for rolipram
D811A/Q812I
-
activity towards 3',5'-cGMP and 3',5'-cAMP is less than 50% of wild-type activity. Slight increase in IC50-value for erythro-9-(2-hydroxy-3-nonyl)adenine, decrease in IC50-value for rolipram
I826V
-
activity towards 3',5'-cGMP is less than 20% of wild-type activity, activity with 3',5'-cAMP is less than 10% of wild-type activity. Increase in IC50-value for erythro-9-(2-hydroxy-3-nonyl)adenine and rolipram
L858M
-
activity towards 3',5'-cGMP is less than 50% of wild-type activity, activity with 3',5'-cAMP is less than 20% of wild-type activity. Slight increase in IC50-value for erythro-9-(2-hydroxy-3-nonyl)adenine, decrease in IC50-value for rolipram
L858S
-
activity towards 3',5'-cGMP is less than 20% of wild-type activity, activity with 3',5'-cAMP is less than 10% of wild-type activity
L907A
-
activity towards 3',5'-cGMP is less than 10% of wild-type activity, activity with 3',5'-cAMP is less than 20% of wild-type activity
Q812I
-
activity towards 3',5'-cGMP is less than 50% of wild-type activity, activity towards 3',5'-cAMP is similar to wild-type activity. Slight increase in IC50-value for erythro-9-(2-hydroxy-3-nonyl)adenine, decrease in IC50-value for rolipram
Q812P
-
activity towards 3',5'-cAMP and 3',5'-cGMP is less than 10% of wild-type activity
Q812P/T819Y
-
activity towards 3',5'-cGMP is less than 20% of wild-type activity, activity with 3',5'-cAMP is less than 20% of wild-type activity
T819Y
-
activity towards 3',5'-cAMP and 3',5'-cGMP is less than 10% of wild-type activity. Increase in IC50-value for erythro-9-(2-hydroxy-3-nonyl)adenine and rolipram
Y827A
-
activity towards 3',5'-cGMP is less than 10% of wild-type activity, activity with 3',5'-cAMP is less than 20% of wild-type activity
Y827F
-
activity towards 3',5'-cGMP is less than 50% of wild-type activity, activity with 3',5'-cAMP is less than 10% of wild-type activity. Increase in IC50-value for erythro-9-(2-hydroxy-3-nonyl)adenine and rolipram
Y827F/L907A
-
activity towards 3',5'-cGMP is less than 20% of wild-type activity, activity with 3',5'-cAMP is less than 10% of wild-type activity
Y827M
-
activity towards 3',5'-cAMP and 3',5'-cGMP is less than 10% of wild-type activity
Y827V
-
activity towards 3',5'-cAMP and 3',5'-cGMP is less than 10% of wild-type activity
D21A
-
90% loss of catalytic activity; specific activity for cAMP hydrolysis is nearly identical to wild-type value
D66A
-
75% of wild-type activity, sigmoidal kinetics with respect to Mn2+; specific activity for cAMP hydrolysis is 4fold lower than wild-type value
D66A
O06629
compromised cAMP hydrolytic activity, crystallization data
H169A
-
60% of wild-type activity; specific activity for cAMP hydrolysis is nearly identical to wild-type value
H207A
-
30% of wild-type activity; specific activity for cAMP hydrolysis is 2.4 fold lower than wild-type value
N97A
-
almost complete loss of activity; specific activity for cAMP hydrolysis is nearly identical to wild-type value
M847L
-
activity towards 3',5'-cGMP is less than10% of wild-type activity, activity with 3',5'-cAMP is less than 20% of wild-type activity
additional information
-
the isolated PDE11 catalytic domain with residues M563-N934 displays both monomeric and dimeric forms. Isoforms containing at least 123 C-terminal amino acids of the GAF-B domain are stable oligomers, while the GAF-A domain is not required for oligomerization
additional information
Q9HCR9, Q9Y233
chimera of isoform PDE10 GAF-domain and cyanobacterial cyclase is stimulated 9fold by cAMP, whereas cGMP has only low activity. CAMP increases Vmax in a non-cooperative manner and does not influence the Km value. Mutation of the D residue within the invariant NKFDE motif of the GAF domain reduces intramolecular signaling considerably; chimera of isoform PDE11 GAF-domain and cyanobacterial cyclase shows non-cooperative 4fold increase in Vmax. Mutation of the D residue within the invariant NKFDE motif of the GAF domain reduces intramolecular signaling considerably
additional information
-
inhibition of isoform PDE1B2 induction by RNAi results. Expression of PDE1B2 short hairpin RNA effectivly suppresses enzyme mRNA, protein, and activity-upregulation upon treatment with phorbol-12-myristate-13-acetate and results in augmented cell spreading, phagocyte ability, and CD11b expression. Enzyme knock-down cells have lower basal levels of cAMP and alterations in the phosphorylation state of several probabl protein kinase A substrate proteins
additional information
-
amino acid residues N845, E866, E971, F972, and F1004 are involved in cAMP (substrate) binding, while Y751, H836, H840, E866, D950 and F1004 participate in cGMP (inhibitor) binding
H23A
-
60% of wild-type activity; specific activity for cAMP hydrolysis is 1.4fold higher than wild-type value
additional information
-
overexpression in Escherichia coli and in Mycobacterium leprae results in reduced intracellular cAMP levels
N97A
O06629
almost complete loss of activity, lacks one of the Mn2+ coordinating residues
additional information
-
enzyme disruption mutants of isoforms PdeA, PdeB, PdeC show normal growth, development, and germination under nonstress conditions. Spore of mutants, especially of PdeA and PdeB, placed under osmotic stress germinate earlier than the wild-type spores. PdeA and PdeB mutants show impaired growth under high-temperature stress, accompanied by increased cyclic AMP levels
additional information
-
construction of a pdeE disruption mutant, phenotype, overview
additional information
-
decrease in enzyme activity by RNAi results in significantly attenuated vascular smoth muscle cell growth by decreasing proliferation via G1 arrest and inducing apoptosis. Application of RNAi also leads to intracellular cGMP elevation, p27Kip1 upregulation, cyclin D1 downregulation, and p53 activation
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
molecular biology
-
assay procedure of calmodulin-dependent cyclic nucleotide phosphodiesterase
medicine
-
PDE11 inhibition has impacts on sperm quality. Reasonable caution is indicated for patients taking the prescribed dosages of tadalafil, a PDE5 inhibitor which could crossreact with human PDE11A splicing variants; PDE11 inhibition has impacts on sperm quality. Reasonable caution should by suggested in patients taking the prescribed dosages of tadalafil, a PDE5 inhibitor which could crossreact with human PDE11A splicing variants
medicine
-
the effect of increasing concentrations of cGMP on endothelial permeability is biphasic, attributable to the relative amounts of enzyme isoforms PDE2A and PDE3A in endothelial 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
-
enzyme inhibitors can reverse the time-dependent forgetting in the object recognition test. The efficacy of the different inhibitors is dependent on the time point of administration after acquisition. Support for a role for cGMP in early stages of memory formation and for cAMP in the late stages of memory formation
medicine
-
PDE2 inhibition improved short-termobject recognition performance after an acute tryptophan depletion induced deficit
medicine
-
inhibition of PDE10A represents an important new target for the treatment of schizophrenia and related disorders of basal ganglia function
medicine
-
genetic disruption or pharmacological inhibition of PDE10A reverses behavioral abnormalities associated with subcortical hyperdopaminergia
molecular biology
-
convenient and sensitive radioenzymatic assay for characterization and determining the contribution if the various PDE families in cell and tissue, PDE11; convenient and sensitive radioenzymatic assay for characterization and determining the contribution of the various PDE families in cell and tissue, PDE1; convenient and sensitive radioenzymatic assay for characterization and determining the contribution of the various PDE families in cell and tissue, PDE10; convenient and sensitive radioenzymatic assay for characterization and determining the contribution of the various PDE families in cell and tissue, PDE2; convenient and sensitive radioenzymatic assay for characterization and determining the contribution of the various PDE families in cell and tissue, PDE3
molecular biology
-
description of a technique used to estimate the extent of PDE1 activation in vivo by measuring in vitro the PDE activity. The technique can be used to measure Ca2+/CaM-stimulated PDE activity in cultured cells or tissues