Information on EC 3.1.4.17 - 3',5'-cyclic-nucleotide phosphodiesterase and Organism(s) Homo sapiens

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


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
3.1.4.17
-
RECOMMENDED NAME
GeneOntology No.
3',5'-cyclic-nucleotide phosphodiesterase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
purine metabolism
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-
Purine metabolism
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-
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.
CAS REGISTRY NUMBER
COMMENTARY hide
9040-59-9
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
cAMP + H2O
AMP
show the reaction diagram
-
-
?
cGMP + H2O
GMP
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
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
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
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
?
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Calmodulin
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mn2+
-
required
Zn2+
-
is coordinated to His529, His563, Asp564, Asp674, and two phosphate oxygen atoms
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2R,3R)-3-(6-amino-9H-purin-9-yl)nonan-2-ol
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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
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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
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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
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time-dependent and irreversible inactivation of PDE3A
3',5'-cGMP
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3'-benzyl-2'-(biphenyl-4-ylmethyl)-5'-methyl-3'H-spiro[cyclopentane-1,7'-imidazo[2,1-b]purin]-4'(5'H)-one
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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
3-isobutyl-1-methylxanthine
3-isobutyl-8-(methoxymethyl)-1-methyl-3,9-dihydro-1H-purine-2,6-dione
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i.e. 8MM-IBMX, comparison of inhibitory effect on several recombinant human PDE isoforms
5-methyl-2-[4-(trifluoromethyl)benzyl]-5,6a,7,8,9,9a-hexahydrocyclopenta[4,5]imidazo[2,1-b]purin-4(1H)-one
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i.e. SCH51866, comparison of inhibitory effect on several recombinant human PDE isoforms. Effective PDE1 inhibitor in cellular context
8-methoxymethyl(-3-isobutyl-1-)methylxanthine
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8-methoxymethyl-3-isobutyl-1-methylxanthine
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0.02 mM selectively inhibits PDE1; 0.02 mM selectively inhibits PDE1
adenosine
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-
Cilostamide
cilostazol
dioclein
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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)
dipyridamole
EHNA
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a selective PDE2 inhibitor
erythro-9-(2-hydroxy-3-nonyl)adenine
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IC50: 0.00061 mM for wild-type enzyme
isobutylmethylxanthine
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inhibits with micromolar potency
Milrinone
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MP-10
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-
papaverine
PQ-10
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quinazolinamine
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IC50: 0.01 mM, PDE3; IC50: 0.23 mM, PDE1; IC50: 0.241 mM, PDE2
rolipram
RP-73401
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IC50: 0.05 mM, PDE3; IC50: 0.067 mM, PDE2; IC50: 0.13 mM, PDE1
sildenafil
tadalafil
TP-10
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vardenafil
vinpocetine
zaprinast
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000079 - 0.032
3',5'-cAMP
0.00002 - 0.034
3',5'-cGMP
0.0017 - 1.6
cAMP
0.0013 - 1
cGMP
additional information
additional information
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-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.3 - 0.52
3',5'-cAMP
4.2
3',5'-cGMP
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catalytic domain of PDE2A (PDE2A residues 578-919), enzyme expressed in Escherichia coli
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0434
(Rp)-guanosine-3',5'-cyclic-S-(4-bromo-2,3-dioxobutyl)monophosphorothioate
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in 45 mM HEPES (pH 7.2), 20 mM MgCl2, and 4 mM MES, at 25°C
0.00002 - 0.00003
3',5'-cGMP
0.000039 - 0.000056
cilostazol
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0043
(2R,3R)-3-(6-amino-9H-purin-9-yl)nonan-2-ol
Homo sapiens;
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IC50: 0.0043 mM, PDE2
0.0023
(2S,3R)-3-(7-amino-3H-imidazo[4,5-b]pyridin-3-yl)nonan-2-ol
Homo sapiens;
-
isoform PDE2, pH and temperature not specified in the publication
0.000006 - 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
0.02654 - 0.0402
3-isobutyl-1-methyl-1H-purine-2,6(3H,7H)-dione
0.0012
cAMP
Homo sapiens;
-
IC50: 1200 nM, PDE11A4
0.000059 - 0.00056
cGMP
0.00013 - 0.221
Cilostamide
0.0382 - 0.1
dioclein
0.00034 - 0.00084
dipyridamole
0.00061
erythro-9-(2-hydroxy-3-nonyl)adenine
Homo sapiens;
-
IC50: 0.00061 mM for wild-type enzyme
0.0127
IBMX
Homo sapiens;
P27815
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0.007
Milrinone
Homo sapiens;
P27815
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0.01 - 0.241
quinazolinamine
0.15
rolipram
Homo sapiens;
-
IC50: 0.15 mM for wild-type enzyme
0.05 - 0.13
RP-73401
0.00035 - 0.0038
sildenafil
0.000015 - 0.01
tadalafil
0.000121 - 0.00084
vardenafil
0.0223
vinpocetine
Homo sapiens;
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IC50: 0.0223 mM
0.00816
zaprinast
Homo sapiens;
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IC50: 0.00816 mM, PDE4A4
0.01
additional information
Homo sapiens;
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IC50 for vardenafil, sildenafil and tadalafil is above 10000 nM, PDE2
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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glioblastoma cell, expression of isoform PDE1C and lower levels of isoforms PDE2, PDE3, PDE4, and PDE5
Manually annotated by BRENDA team
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lung epithelial cell
Manually annotated by BRENDA team
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activity is one-tenth compared to normal tissue
Manually annotated by BRENDA team
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phosphodiesterase 3 is exclusively detected in smooth muscle cells of the wall, no activity in vascular endothelial layer
Manually annotated by BRENDA team
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external layer of
Manually annotated by BRENDA team
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predominant expression of isoform PDE1A
Manually annotated by BRENDA team
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epithelial cells and macrophages
Manually annotated by BRENDA team
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myometrial cell, level of isoform PDE1C decreases in all conditions that inhibit proliferation
Manually annotated by BRENDA team
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cultured, PDE1; cultured, PDE3
Manually annotated by BRENDA team
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main distribution in glandular and subglandular areas
Manually annotated by BRENDA team
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of central cavernous arteries
Manually annotated by BRENDA team
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PDE1; PDE2; PDE3
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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PDE2A2 and PDE2A3, and PDE3A and PDE3B
Manually annotated by BRENDA team
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PDE2A1
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Manually annotated by BRENDA team
PDB
SCOP
CATH
UNIPROT
ORGANISM
Homo sapiens;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
55000
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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
56000
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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
60000
-
2 * 60000
61000
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2 * 61000
64000
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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
65800
x * 65800, deduced from gene sequence
66000
-
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
72000
-
x * 72000, splice variant PDE1C1, x * 75000, splice variant PDE1C3
78000
-
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
78100
x * 78100, deduced from gene sequence
100000
-
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
105000
-
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
110000
-
isoform PDE11A2, gel filtration
124000
-
-
140000
190000
-
isoform PDE11A4, gel filtration
220000
-
isoform PDE11A1, gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
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in adipocytes, insulin induces formation of macromolecular complexes containing signaling molecules such as IRS-1, PI3K and PKB, proteins involved in PDE3B activation/phosphorylation
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
vapor diffusion method, crystal structure of the catalytic domain of PDE2A (PDE2A residues 578-919) determined at 1.7 A resolution
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2500-3000fold
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anion exchange chromatography
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nickel resin column chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
baculovirus expression system, PDE11A4
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Epac1-camps-PDE3A fusion protein is expressed in HEK-293 cells
expressed in a baculovirus/insect cell Sf9 system
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expression by using a baculovirus expression system
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expression in COS-7 cells
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expression in insect cells or in Escherichia coli
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expression in NIH3006 murine fibroblasts and baculovirus-infected Sf9 insect cells
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expression in Saccharomyces cerevisiae
PDE3A expression in HEK-293 cells on the plasma membrane
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
epinephrine infusion stimulates skeletal muscle PDE2A expression
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D106A
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mutation does not influence h-prune phosphodiesterase activity
D811A
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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
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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
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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
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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
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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
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
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
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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
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine