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Information on EC 3.1.4.1 - phosphodiesterase I and Organism(s) Mus musculus and UniProt Accession P70158
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3.1.4.1 phosphodiesterase IIUBMB Comments
Hydrolyses both ribonucleotides and deoxyribonucleotides. Has low activity towards polynucleotides. A 3'-phosphate terminus on the substrate inhibits hydrolysis.
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Word Map
- 3.1.4.1
- camp
- phosphodiesterases
- calcification
- arterial
-
topoisomerase
- rolipram
- monophosphate
-
camp-specific
-
infancy
- osteoblast
-
hypophosphatemic
- rickets
- camptothecin
-
pseudoxanthoma
-
ectoenzyme
- topotecan
-
5'-nucleotide
- elasticum
- ibmx
- ankylosis
- 3'-phosphate
- zaprinast
-
top1-dna
- camp-pde
-
tcf7l2
- milrinone
-
tissue-nonspecific
-
cgmp-inhibited
-
cgmp-stimulated
-
pyrophosphohydrolase
- cilomilast
-
cementum
- 3-isobutyl-1-methylxanthine
-
rolipram-sensitive
- vinpocetine
-
cardiotonic
- pharmacology
- medicine
- synthesis
- drug development
- biotechnology
- analysis
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
enpp1, pde4a, phosphodiesterase i, pde i, tyrosyl-dna phosphodiesterase 1, ectonucleotide pyrophosphatase/phosphodiesterase 1, nucleotide phosphodiesterase, cpsf-73, 5'-phosphodiesterase, ectonucleotide pyrophosphatase phosphodiesterase 1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
5'-exonuclease
-
-
-
-
5'-nucleotide phosphodiesterase
-
-
-
-
5'-phosphodiesterase
-
-
-
-
nucleotide pyrophosphatase/alkaline phosphodiesterase I
-
EC 3.6.1.9 /EC 3.1.4.1
orthophosphoric diester phosphohydrolase
-
-
-
-
PC-1
phosphodiesterase 1C
PC-1
-
PC-1, plasma-cell differentiation antigen-1, membrane glycoprotein, has 5'-nucleotide phosphodiesterase and nucleotide pyrophosphatase activity
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
catalytic mechanism, the enzyme has a unique catalytic cycle, structure-function analysis overview
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoric ester hydrolysis
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
oligonucleotide 5'-nucleotidohydrolase
Hydrolyses both ribonucleotides and deoxyribonucleotides. Has low activity towards polynucleotides. A 3'-phosphate terminus on the substrate inhibits hydrolysis.
CAS REGISTRY NUMBER
COMMENTARY
9025-82-5
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
-
PC-1
-
-
?
p-nitrophenyl phenylphosphonate + H2O
p-nitrophenol + benzenephosphonic acid
-
-
-
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
-
-
-
-
?
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
-
PC-1
-
-
?
cyclic 3',5'-mononucleotides + H2O
mononucleoside 5'-phosphate
-
PC-1
-
-
?
cyclic 3',5'-mononucleotides + H2O
mononucleoside 5'-phosphate
-
phosphodiester bonds
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
-
enzyme hydrolyzes single-stranded DNA, no activity with double-stranded DNA
-
-
?
additional information
?
-
-
PC-1, PC-1 may take part in purine uptake for metabolic needs of cells
-
-
?
additional information
?
-
-
PC-1, PC-1 may take part in purine uptake for metabolic needs of cells
-
-
?
additional information
?
-
-
PC-1, nucleotide pyrophosphatase/alkaline phosphodiesterase I, may have a role in the regulation of N-linked glycosylation, it may regulate the availability of nucleotide sugar precusors at the site of oligosaccharide synthesis
-
-
?
additional information
?
-
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
PC-1, PC-1 may take part in purine uptake for metabolic needs of cells
-
-
?
additional information
?
-
-
PC-1, PC-1 may take part in purine uptake for metabolic needs of cells
-
-
?
additional information
?
-
-
PC-1, nucleotide pyrophosphatase/alkaline phosphodiesterase I, may have a role in the regulation of N-linked glycosylation, it may regulate the availability of nucleotide sugar precusors at the site of oligosaccharide synthesis
-
-
?
additional information
?
-
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Ca2+
-
dependent on, a calcium sensing receptor (CaSR) activation decreases cAMP and renin release and stimulates calcium calmodulin-activated phosphodiesterase
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
8-methoxymethyl isobutylmethylxanthine
-
20 microM, 8-MM-IBMX, a selective PDE1 inhibitor, no effect on either JG cell cAMP content or renin release compared to untreated controls
isobutylmethylxanthine
-
100 microM, a nonselective PDE1 inhibitor, increases cAMP and renin relase by 72% and 118%, respectively
N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide
-
W7, 10 microM, a calcium-calmodulin inhibitor
additional information
PC-1 promoter activity induced by osteoblast differentiation is inhibited by fibroblast growth factor 2
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
PC-1 promoter activity increases with calvarial osteoblast differentiation
-
additional information
etoposide and doxorubicin trigger a series of events that eventually lead to an enhanced DNA-linkage of topo I, which then is acted upon by the enzyme TDP1
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0015
-
wild-type protein, in the absence of Ca2+, reflecting the basal PDE activity in the cilia, 37°C, pH not specified in the publication
0.0034
-
wild-type cilial PDE, supplemented with Ca2+ and calmodulin, 2.3fold increased compared compared to the assay without Ca2+, 37°C, pH not specified in the publication
additional information
-
no basal activity is detected using the Pde1-/- knockout mutant in the standard assay and also the addition of Ca2+/calmodulin does not elicit any PDE acitivty
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
JG cells, isoform 1C, isolated from 8-to 10-week-old C57/BL6 mice, cells in the kidney which synthesize, store and release renin (EC 3.4.23.15)
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OSN cilia, PDE1C is detected primarily in the cilial layer, whereas PDE4A is detected in OSN cell bodies, dentrites and axons. The loss of one of the PDEs does not effect the occurrence of the other PDE. The localization of the PDE4A protein is normal in PDE1c-/- knockout mutant mice and vice versa
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
PC-1, active site of plasma-membrane-associated PC-1 appears to be located extracellularly
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the enzyme is a member of the metallophosphoesterase enzyme family, the molecular mass of secreted SMPDL3A is tissue and/or species dependent
evolution
the enzyme belongs to the phospholipase D, PLD, superfamily, which consists of a highly diverse collection of prokaryotic and eukaryotic enzymes, such as bacterial, plant and mammalian PLDs, cardiolipin and phosphatidylserine synthases, Salmonella typhimurium Nuc and mammalian DNase II endonucleases, restriction enzyme BfiI, poxvirus envelope proteins p37K and K4L, and eukaryotic Tdp1, sequence comparison. Family members show the presence of two histidine-lysine-aspartate-asparagine-HKDN-(HxKx4Dx6N; x being any amino acid) motifs
malfunction
physiological function
tyrosyl-DNA phosphodiesterase I is a eukaryotic DNA repair enzyme that catalyzes the removal of covalent 3'-DNA adducts, the enzyme hydrolyzes the 3'-phospho-tyrosyl that in the cell covalently links DNA topoisomerase I and DNA. The enzyme plays a role in suppressing etoposide-induced DNA damage
malfunction
-
Pde1c-/- and Pde4a-/- knockout mutants to examine the role of the PDEs in olfactory transduction. Pde1c-/- OSNs (olfactory sensory neuron cilia) show reduced sensitivity and attenuated adaptation to repeated stimulation, suggesting that PDE1C may be involved in regulating sensitivity and adaptation
malfunction
Tdp1-/- enzyme knockout mice do not show increased sensitivity to etoposide, i.e. VP16
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
67000
-
tumor cell line, N-ethylmaleimide-sensitive, gel filtration and SDS-PAGE
80000
-
Western blot analysis of PDE 1A, 1B, and 1C to determine which phosphodiesterase isoform is involved in inhibition of renin release. In conclusion isoform 1C is expressed in isolated JG cells
additional information
molecular mass of secreted SMPDL3A is tissue and/or species dependent
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
Pde1c-/- and Pde4a-/- knockout mutants to examine the role of the PDEs in olfactory transduction. Pde1c-/- OSNs (olfactory sensory neuron cilia) show reduced sensitivity and attenuated adaptation to repeated stimulation, suggesting that PDE1C may be involved in regulating sensitivity and adaptation
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
dithiothreitol stabilizes, the absence of dithiothreitol during purification results in rapid inactivation
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
nucleotide pyrophosphatase/alkaline phosphodiesterase I, transformed into Escherichia coli
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Fukazawa, H.; Nishimura, T.; Tanaka, N.; Suzuki, H.
5'-Nucleotide phosphodiesterase and alkaline phosphatase in tumor cells: evidence for existence of novel species in the cytosol
Biochim. Biophys. Acta
966
99-106
1988
Bos taurus, Homo sapiens, Mus musculus
Fukazawa, H.; Suzuki, H.; Tanaka, N.
A novel tumor-associated molecular species of 5'-nucleotide phosphodiesterase
Biochem. Biophys. Res. Commun.
130
1072-1077
1985
Mus musculus
Belli, S.I.; van Driel, I.R.; Goding, J.W.
Identification and characterization of a soluble form of the plasma cell membrane glycoprotein PC-1 (5'-nucleotide phosphodiesterase)
Eur. J. Biochem.
217
421-428
1993
Mus musculus
Belli, S.I.; Goding, J.W.
Biochemical characterization of human PC-1, an enzyme possessing alkaline phosphodiesterase I and nucleotide pyrophosphatase activities
Eur. J. Biochem.
226
433-443
1994
Homo sapiens, Mus musculus
Rebbe, N.F.; Tong, B.D.; Finley, E.M.; Hickman, S.
Identification of nucleotide pyrophosphatase/alkaline phosphodiesterase I activity associated with the mouse plasma cell differentiation antigen PC-1
Proc. Natl. Acad. Sci. USA
88
5192-5196
1991
Mus musculus, Mus musculus BALB/c
Hatch, N.E.; Franceschi, R.T.
Osteoblast differentiation stage-specific expression of the pyrophosphate-generating enzyme PC-1
Cells Tissues Organs
189
65-69
2009
Mus musculus (P06802)
Yang, X.C.; Sullivan, K.D.; Marzluff, W.F.; Dominski, Z.
Studies of the 5' exonuclease and endonuclease activities of CPSF-73 in histone pre-mRNA processing
Mol. Cell. Biol.
29
31-42
2009
Mus musculus
Ortiz-Capisano, M.C.; Liao, T.D.; Ortiz, P.A.; Beierwaltes, W.H.
Calcium-dependent phosphodiesterase 1C inhibits renin release from isolated juxtaglomerular cells
Am. J. Physiol. Regul. Integr. Comp. Physiol.
297
R1469-R1476
2009
Mus musculus
Cygnar, K.D.; Zhao, H.
Phosphodiesterase 1C is dispensable for rapid response termination of olfactory sensory neurons
Nat. Neurosci.
12
454-462
2009
Mus musculus
Comeaux, E.Q.; van Waardenburg, R.C.
Tyrosyl-DNA phosphodiesterase I resolves both naturally and chemically induced DNA adducts and its potential as a therapeutic target
Drug Metab. Rev.
46
494-507
2014
Canis lupus familiaris (E2REL5), Gallus gallus (F1NSQ5), Saccharomyces cerevisiae (P38319), Rattus norvegicus (Q4G056), Mus musculus (Q8BJ37), Homo sapiens (Q9NUW8), Drosophila melanogaster (Q9VQM4), Saccharomyces cerevisiae ATCC 204508 (P38319)
Traini, M.; Quinn, C.M.; Sandoval, C.; Johansson, E.; Schroder, K.; Kockx, M.; Meikle, P.J.; Jessup, W.; Kritharides, L.
Sphingomyelin phosphodiesterase-like 3A (SMPDL3A) is a novel nucleotide phosphodiesterase regulated by cholesterol in human macrophages
J. Biol. Chem.
289
32895-32913
2014
Mus musculus (P70158), Homo sapiens (Q92484), Homo sapiens, Mus musculus C57 black (P70158)
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