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Information on EC 3.1.16.1 - spleen exonuclease
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3.1.16.1 spleen exonucleaseSpecify your search results
Word Map
- 3.1.16.1
- flap
-
endonuclease-1
-
structure-specific
-
okazaki
- nucleases
-
micrococcal
-
snake
- polynucleotide
-
5'-flaps
-
32p-postlabeling
- 3'-monophosphate
-
long-patch
-
lagging-strand
- 2'-deoxyguanosine
- 5'-exonuclease
-
exonucleolytic
-
dinucleoside
- fen1
- analysis
-
internucleotide
The expected taxonomic range for this enzyme is: Eukaryota, Archaea
Reaction Schemes
exonucleolytic cleavage in the 5'- to 3'-direction to yield nucleoside 3'-phosphates
Synonyms
fen-1, spleen phosphodiesterase, phosphodiesterase ii, 5'-to-3' exonuclease, spleen exonuclease, trm2p, nucleotide pyrophosphatase/phosphodiesterase 1, beef spleen exonuclease, 3'-nucleotide phosphodiesterase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
EC 3.1.4.18
-
-
formerly
-
FEN-1
flap endonuclease-1
phosphodiesterase II
spleen phosphodiesterase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
exonucleolytic cleavage in the 5'- to 3'-direction to yield nucleoside 3'-phosphates
also degradation of thymine and adenine polynucleotides to thymine and adenine
-
exonucleolytic cleavage in the 5'- to 3'-direction to yield nucleoside 3'-phosphates
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
9068-54-6
-
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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
4-methylumbelliferyl thymidine 3'-phosphate + H2O
thymidine 3'-phosphate + 4-methylumbelliferone
-
-
-
?
5'-hydroxy oligonucleotides + H2O
nucleoside 3'-oligonucleotides + nucleoside 3'-phosphates
5-'deoxy-5'-chlorothymidine-3'-(4-nitrophenyl)phosphate + H2O
5'-deoxy-5'-chlorothymidine-3'-phosphate
-
-
-
?
mRNA + H2O
?
-
XRNA is important in the degradation of deadenylated mRNAs in trypanosomes
-
-
?
polynucleotides + H2O
phosphomononucleotides
-
the enzyme contributes to the turnover of messenger RNAs in eukaryotic cells
-
-
?
thymidine 3'-(2,4-dinitrophenyl)phosphate + H2O
thymidine 3'-phosphate + 2,4-dinitrophenol
[PO/Mix-PS]-d[TPOCPOTPOTPOTPOTPOTPSC] + H2O
?
-
21% degraded after 2 hours, 35% degraded after 8 hours
-
-
?
[PO/Mix-PS]-d[TPOTPOTPOTPOTPOTPOTPOTPOTPOTPOTPST] + H2O
?
-
35% degraded after 2 hours, 75% degraded after 8 hours
-
-
?
[PO/RP-PS]-d[TPOCPOTPOTPOTPOTPOTPSC] + H2O
?
-
22% degraded after 2 hours, 45% degraded after 8 hours
-
-
?
[PO/SP-PS]-d[TPOCPOTPOTPOTPOTPOTPSC] + H2O
?
-
20% degraded after 2 hours, 25% degraded after 8 hours
-
-
?
[RP-PS]-d[T12] + H2O
?
-
25% degraded after 2 hours, 75% degraded after 8 hours
-
-
?
3'-phospho-2'-deoxyribooligonucleotide + H2O
2'-deoxyribonucleoside 3'-phosphate
-
dinucleotides
-
-
?
3'-phospho-2'-deoxyribooligonucleotide + H2O
2'-deoxyribonucleoside 3'-phosphate
-
-
-
?
3'-phospho-2'-deoxyribooligonucleotide + H2O
2'-deoxyribonucleoside 3'-phosphate
-
-
-
?
3'-phospho-2'-deoxyribooligonucleotide + H2O
2'-deoxyribonucleoside 3'-phosphate
-
average size 10-12, smallest 3
-
?
3'-phospho-2'-deoxyribooligonucleotide + H2O
2'-deoxyribonucleoside 3'-phosphate
-
methylated by dimethyl sulfate
-
?
3'-phospho-2'-deoxyribooligonucleotide + H2O
2'-deoxyribonucleoside 3'-phosphate
-
size of oligonucleotides 4-9
-
?
5'-hydroxy oligonucleotides + H2O
nucleoside 3'-oligonucleotides + nucleoside 3'-phosphates
-
3',5'-diribonucleoside phosphates and analoga
-
?
5'-hydroxy oligonucleotides + H2O
nucleoside 3'-oligonucleotides + nucleoside 3'-phosphates
-
dependency on type of nucleobase
-
?
5'-hydroxy oligonucleotides + H2O
nucleoside 3'-oligonucleotides + nucleoside 3'-phosphates
-
no hydrolysis of 2'-5' and 5'-5' internucleotide bonds and CpC and CpU-linkages
-
?
5'-hydroxy oligonucleotides + H2O
nucleoside 3'-oligonucleotides + nucleoside 3'-phosphates
-
5'-hydroxy-thymidine oligonucleotides , 5'-hydroxy-adenine oligonucleotides, 5'-hydroxy-2'-deoxycytidine oligonucleotides and various other 5'-hydroxy- and 5'-hydroxy-2'deoxy oligonucleotides like ApUp, d-TpTpC
-
r
5'-hydroxy oligonucleotides + H2O
nucleoside 3'-oligonucleotides + nucleoside 3'-phosphates
-
dependency on type of nucleobase
-
?
bis-(4-nitrophenyl)phosphate + H2O
4-nitrophenyl phosphate + 4-nitrophenol
-
-
-
?
bis-(4-nitrophenyl)phosphate + H2O
4-nitrophenyl phosphate + 4-nitrophenol
-
-
-
?
DNA + H2O
deoxyribonucleoside 3'-phosphates
-
denatured only, no native or double stranded
-
?
DNA + H2O
deoxyribonucleoside 3'-phosphates
-
Ape2 preferentially removes mismatched 3'-nucleotides from DNA
-
-
?
DNA + H2O
deoxyribonucleoside 3'-phosphates
-
Trm2p displays 5' to 3' exonuclease activity on double-strand DNA, and endonuclease activity on single-strand DNA
-
-
?
DNA + H2O
deoxyribonucleoside 3'-phosphates
-
alkali-denaturated DNA, 25 times lower degradation rate with native DNA
-
?
DNA + H2O
deoxyribonucleoside 3'-phosphates
-
5'-OH and 5'-P DNA with chain length of 100-2500
-
?
polyadenylic acid + H2O
5'-hydroxy-adenine oligonucleotides + 3'AMP
-
-
-
r
polyadenylic acid + H2O
5'-hydroxy-adenine oligonucleotides + 3'AMP
-
-
-
?
polynucleotides + H2O
3'-phosphomononucleotides
-
involvement in DNA repair and replication, genetic recombination, elimination of damaged nucleotides
-
?
polynucleotides + H2O
3'-phosphomononucleotides
-
involvement in DNA repair and replication, genetic recombination, elimination of damaged nucleotides
-
?
polynucleotides + H2O
3'-phosphomononucleotides
-
5' -> 3' exonuclease Xrn2 promotes transcription termination at co-transcriptional cleavage sites
-
-
?
ribonucleotide 3'-alkyl esters + H2O
3'-Ribonucleotides + alkyl alcohol
-
-
-
?
ribonucleotide 3'-alkyl esters + H2O
3'-Ribonucleotides + alkyl alcohol
-
-
-
r
RNA core + H2O
nucleoside 3'-phosphates
-
RNA core are water undializable 3'-phosphoribooligonucleotides obtained by exhaustive digestion of RNA with pancreatic ribonuclease
-
?
thymidine 3'-(2,4-dinitrophenyl)phosphate + H2O
thymidine 3'-phosphate + 2,4-dinitrophenol
-
-
-
?
thymidine 3'-(2,4-dinitrophenyl)phosphate + H2O
thymidine 3'-phosphate + 2,4-dinitrophenol
-
-
-
?
thymidine 3'-(2,4-dinitrophenyl)phosphate + H2O
thymidine 3'-phosphate + 2,4-dinitrophenol
-
-
-
?
thymidine 3'-(2,4-dinitrophenyl)phosphate + H2O
thymidine 3'-phosphate + 2,4-dinitrophenol
-
-
-
?
thymidine 3'-(4-nitrophenyl)phosphate + H2O
thymidine 3'-phosphate + 4-nitrophenol
-
-
-
?
thymidine 3'-(4-nitrophenyl)phosphate + H2O
thymidine 3'-phosphate + 4-nitrophenol
-
-
-
?
thymidine 3'-(4-nitrophenyl)phosphate + H2O
thymidine 3'-phosphate + 4-nitrophenol
-
-
-
?
thymidine 3'-(4-nitrophenyl)phosphate + H2O
thymidine 3'-phosphate + 4-nitrophenol
-
-
-
?
thymidine 3'-(4-nitrophenyl)phosphate + H2O
thymidine 3'-phosphate + 4-nitrophenol
-
-
-
?
thymidine 3'-(4-nitrophenyl)phosphate + H2O
thymidine 3'-phosphate + 4-nitrophenol
-
-
-
?
thymidine 3'-(4-nitrophenyl)phosphate + H2O
thymidine 3'-phosphate + 4-nitrophenol
-
very slow hydrolysis
-
?
tRNA + H2O
tRNA fragments + nucleoside 3'-phosphates
-
5'-phosphoryl terminus hydrolysed by contaminating endonucleases
-
?
tRNA + H2O
tRNA fragments + nucleoside 3'-phosphates
-
phosphorylated or dephosphorylated at 5'-terminus
-
?
tRNA + H2O
tRNA fragments + nucleoside 3'-phosphates
-
from Escherichia coli
-
?
additional information
?
-
-
[RP-but last one-PS]-d[T12] is not hydrolyzed
-
-
?
additional information
?
-
-
NurA may function closely together with SSB in DNA transactions in archaea
-
-
?
additional information
?
-
-
NurA has ssDNA endonuclease, 5'-3' ssDNA exonuclease, and 5'-3' dsDNA exonuclease activities, overview. NurA is closely linked to Mre11 and Rad50 homologues, it interacts with single-stranded DNA-binding protein, StoSSB, from the hyperthermophilic archaeon Sulfolobus tokodaii, determination by pull-down assay using Ni-NTA agarose beads and MALDI-TOF mass spectrometry, and yeast two-hybrid and co-immunoprecipitation analysis, overview. Substrates are 34-bp dsDNA and M13mp18 ssDNA
-
-
?
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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
polynucleotides + H2O
phosphomononucleotides
-
the enzyme contributes to the turnover of messenger RNAs in eukaryotic cells
-
-
?
additional information
?
-
-
NurA may function closely together with SSB in DNA transactions in archaea
-
-
?
polynucleotides + H2O
3'-phosphomononucleotides
-
involvement in DNA repair and replication, genetic recombination, elimination of damaged nucleotides
-
?
polynucleotides + H2O
3'-phosphomononucleotides
-
involvement in DNA repair and replication, genetic recombination, elimination of damaged nucleotides
-
?
polynucleotides + H2O
3'-phosphomononucleotides
-
5' -> 3' exonuclease Xrn2 promotes transcription termination at co-transcriptional cleavage sites
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mn2+
additional information
Mg2+
yields the highest activity for FEN-1, activity is stimulated above 0.1 mM, reaching a maximum at ca. 10 mM
additional information
Ni2+ or Mn2+ does not have a pronounced stimulatory effect
additional information
-
Ni2+ or Mn2+ does not have a pronounced stimulatory effect
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
dimethyl sulfate
-
inhibition after methylation of 2'-deoxyribooligonucleotides with dimethyl sulfate
glycosylation
-
no activity with glycosylated oligonucleotides obtained from T4 phage DNA
-
KCl
FEN-1 retains up to approximately 70.0% of its endonuclease at 0-50.0 mM, between 75 and 100 mM FEN-1 displays a significant reduction in activity and at the highest salt concentrations between 125-200 mM almost a complete ablation of activity occurres
Pentamidine
-
endo-exonuclease inhibitor, inhibits DNase activity of CBP-Trm2p
RNAi
-
down-regulation of expression by tetracycline-inducible RNA interference
-
single-stranded DNA-binding protein
-
i.e. StoSSB, from the hyperthermophilic archaeon Sulfolobus tokodaii, StoSSB inhibits the exonuclease activity of StoNurA on ssDNA and dsDNA
-
high ionic strength
-
slightly greater inhibition of rat than of guinea-pig enzyme at sodium succinate buffer concentrations greater 0.4 M, also markedly inhibition by 6 M NaCl and 2 M ammonium sulfate
-
high ionic strength
-
slightly greater inhibition of rat than of guinea-pig enzyme at sodium succinate buffer concentrations greater 0.4 M, also markedly inhibition by 6 M NaCl and 2 M ammonium sulfate
-
Mg2+
-
almost no degradation of tRNA at higher concentrations with 1 Mg2+ per nucleotide phosphate
NaCl
-
at 100 mM Ape2 exhibits only 20% of its exonuclease activity, in the presence of 200 mM salt almost no exonuclease activity
NaCl
FEN-1 retains up to approximately 70.0% of its endonuclease at 0-50.0 mM, between 75 and 100 mM FEN-1 displays a significant reduction in activity and at the highest salt concentrations between 125-200 mM almost a complete ablation of activity occurres
Urea
-
after 2 h incubation almost 80% of activity with 1.0 M, 40% with 2.0 M, no activity with 5.0 M
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Chondrocalcinosis
Inhibition of nucleotide pyrophosphatase/phosphodiesterase 1: implications for developing a calcium pyrophosphate deposition disease modifying drug.
Genetic Diseases, Inborn
Human FEN-1 can process the 5'-flap DNA of CTG/CAG triplet repeat derived from human genetic diseases by length and sequence dependent manner.
Genetic Diseases, Inborn
Structure of the DNA repair and replication endonuclease and exonuclease FEN-1: coupling DNA and PCNA binding to FEN-1 activity.
Herpes Simplex
Picornavirus internal ribosome entry site elements target RNA cleavage events induced by the herpes simplex virus virion host shutoff protein.
Huntington Disease
Nuclease-deficient FEN-1 blocks Rad51/BRCA1-mediated repair and causes trinucleotide repeat instability.
Infections
A noncoding RNA produced by arthropod-borne flaviviruses inhibits the cellular exoribonuclease XRN1 and alters host mRNA stability.
Leukemia
Down-regulation of human FEN-1 gene expression during differentiation of promyelocytic leukemia cells.
Leukemia
Gene expression of flap endonuclease-1 during cell proliferation and differentiation.
Melanoma
Catechols and 3-hydroxypyridones as inhibitors of the DNA repair complex ERCC1-XPF.
Neoplasms
Cloning of the Flap Endonuclease-1 Gene in Bombyx mori and Identification of an Antiapoptotic Function.
Neoplasms
Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score.
Neoplasms
Structure of the DNA repair and replication endonuclease and exonuclease FEN-1: coupling DNA and PCNA binding to FEN-1 activity.
Neuroblastoma
Role of phosphodiesterase II in cross talk between cGMP and cAMP in human neuroblastoma NB-OK-1 cells.
Ovarian Neoplasms
Immunohistochemical characterization of a monoclonal antibody detecting an endometrioid ovarian cancer-associated antigen.
Prostatic Neoplasms
Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score.
Sarcoma
Nucleases and adenosine 3',5'-cyclic monophosphate phosphodiesterase activities in murine sarcoma virus (Moloney)-infected mice.
Virus Diseases
Nucleases and adenosine 3',5'-cyclic monophosphate phosphodiesterase activities in murine sarcoma virus (Moloney)-infected mice.
Werner Syndrome
Novel function of the flap endonuclease 1 complex in processing stalled DNA replication forks.
Xeroderma Pigmentosum
The DNA repair endonuclease XPG binds to proliferating cell nuclear antigen (PCNA) and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.071
pyridoxal 5'phosphate-6-azophenyl-2',4'-disulfonic acid
Homo sapiens
-
inhibition of degradation of [PO]-d[TCCTCTTTTTTT]
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
43.3
58.3
646
-
with 5-'deoxy-5'-chlorothymidine-3'-(4-nitrophenyl)phosphate as substrate, 1.5 microg/ml commercially available enzyme
855
-
with thymidine 3'-(4-nitrophenyl)phosphate as substrate, 1.5 microg/ml commercially available enzyme
43.3
-
with 5'-hydroxy-thymidine oligonucleotide TpT, lacking terminal phosphomonoester group, as substrate
43.3
-
with 5'-hydroxy-thymidine oligonucleotide TpTpTpT, lacking terminal phosphomonoester group, as substrate
43.3
-
with 5'-hydroxy-2'deoxy-cytosine oligonucleotide d-CpCpC, lacking terminal phosphomonoester group, as substrate
58.3
-
with 5'-hydroxy-adenine oligonucleotide ApApA, lacking terminal phosphomonoester group, as substrate
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.9 - 6.5
-
5.9 with almost 0.15 M ammonium succinate buffer, 6.5 with almost 0.3 M and thymidine 3'(4-nitrophenyl)phosphate as substrate
6 - 6.5