Information on EC 4.2.99.18 - DNA-(apurinic or apyrimidinic site) lyase and Organism(s) Mus musculus and UniProt Accession O35980

for references in articles please use BRENDA:EC4.2.99.18
Word Map on EC 4.2.99.18
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:
This record set is specific for:
Mus musculus
UNIPROT: O35980
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)


The taxonomic range for the selected organisms is: Mus musculus

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
4.2.99.18
-
RECOMMENDED NAME
GeneOntology No.
DNA-(apurinic or apyrimidinic site) lyase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
endonuclease reaction
exonuclease reaction
-
-
SYSTEMATIC NAME
IUBMB Comments
DNA-(apurinic or apyrimidinic site) 5'-phosphomonoester-lyase
'Nicking' of the phosphodiester bond is due to a lyase-type reaction, not hydrolysis. This group of enzymes was previously listed as endonucleases, under EC 3.1.25.2.
CAS REGISTRY NUMBER
COMMENTARY hide
60184-90-9
-
61811-29-8
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
DNA
fragments of DNA
show the reaction diagram
5'-TCGAGGATCCTGAGCTCGAGTCGACGXTCGCGAATTCTGCGGATCCAAGC-3'
?
show the reaction diagram
a synthetic stable AP-site analog where X represents tetrahydrofuran
-
-
?
DNA
fragments of DNA
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
DNA
fragments of DNA
show the reaction diagram
O35980
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Co2+
-
stimulation
K+
-
25 mM included in assay medium. DNA structures with a nick and DNArec used for photoaffinity modification are substrates for APE1 3'-5'-exonuclease activity, that is more efficient at decreased salt concentrations.
NaCl
-
enzyme form A: optimal activity in 20 mM NaCl or KCl, enzyme form B: more active without salt
Zn2+
-
stimulation half as effective as with Mg2+
additional information
-
presence of divalent cations does not stimulate the activity
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Ca2+
-
complete inhibition at 2 mM
cycloheximide
-
treatment decreases APEX1 protein levels as compared with untreated mouse hepatocytes
E3330
-
APE1 redox-specific inhibitor. E3330 suppresses secretion of inflammatory cytokines including tumor necrosis factor-alpha, interleukin IL-6 and IL-12 and inflammatory mediators nitric oxide as well as prostaglandin E2 from lipopolysaccharide-stimulated RAW264.7 cells and leads to down-regulation of the lipopolysaccharide-dependent expression of inducible nitric oxide synthase and cyclooxygenase-2 genes in the RAW264.7 cells. The effects of E3330 are mediated by the inhibition of transcription factors nuclear factor-kappaB and activator protein 1 in lipopolysaccharide-stimulated macrophages
EDTA
-
complete inhibition at 2 mM
granzyme A
-
granzyme A cleaves APE1 at Lys31 and inactivates it
-
human X-ray repair cross-complementing group 1 protein (XRCC1)
-
at high XRCC1 concentrations, inhibition of APE1 exonuclease activity is observed
-
isoflavones
-
soy isoflavones decrease apurinic/apyrimidinic endonuclease 1/redox factor-1 expression
Kainic acid
-
APE/Ref-1 is decreased by kainic acid injury in a time-dependent manner at the level of proteins, not transcripts
Sodium citrate
-
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
human X-ray repair cross-complementing group 1 protein
-
stimulates APendonuclease and 3'-phosphodiesterase activities of APE1 and increases efficiency of 3'-5'-exonuclease excision of the match as well as noncanonical pairs by APE1
-
oxidative stress
-
-
-
S-adenosylmethionine
-
S-adenosylmethionine co-treatment is able to increase APEX1 protein levels
Triton X-100
-
no stimulation
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00091
5'-TCGAGGATCCTGAGCTCGAGTCGACGXTCGCGAATTCTGCGGATCCAAGC-3'
pH 7.5, 37°C
-
0.0000027
apurinic site
-
37°C, pH 8
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4.2
5'-TCGAGGATCCTGAGCTCGAGTCGACGXTCGCGAATTCTGCGGATCCAAGC-3'
pH 7.5, 37°C
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0000015
-
age-dependent modulation of APE activity in mouse liver organelles, 4-months, mitochondria
0.0000096
-
age-dependent modulation of APE activity in mouse liver organelles, 10-months, mitochondria; age-dependent modulation of APE activity in mouse liver organelles, 20-months, mitochondria
0.0000196
-
age-dependent modulation of APE activity in mouse liver organelles, 10-months, total extract
0.0000232
-
age-dependent modulation of APE activity in mouse liver organelles, 20-months, total extract
0.0000236
-
age-dependent modulation of APE activity in mouse liver organelles, 4-months, total extract
0.000038
-
age-dependent modulation of APE activity in mouse liver organelles, 4-months, nuclear
0.0000485
-
age-dependent modulation of APE activity in mouse liver organelles, 10-months, nuclear
0.000072
-
age-dependent modulation of APE activity in mouse liver organelles, 20-months, nuclear
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 7.5
-
enzyme form B
6.5 - 9
-
enzyme form A
7
-
assay at
7.5 - 8.7
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 10.5
-
pH 6.5: about 25% of activity maximum, pH 10.5: about 20% of activity maximum
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8
calculated from DNA sequence
10
calculated from DNA sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
primary cell line, murine B-cells are isolated from spleen by a negative depletion
Manually annotated by BRENDA team
-
from 2- to 3-month-old male C57/B6 mice isolated by collagenase perfusion
Manually annotated by BRENDA team
-
embryonic fibroblast cell
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
-
APE/Ref-1 is equally distributed between the nucleus and the cytoplasm, whereas at 24 hours, the CD40-induced-B cell activation relocalized APE/Ref-1 in the nucleus
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
36000
SDS-PAGE
28000
-
gel filtration
37000
-
calculated and affirmed by immunoprecipitation
61000
-
sedimentation data
65000
-
1 * 65000, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
-
1 * 65000, SDS-PAGE
additional information
-
enzyme has a DNA repair domain at the C-terminus and a redox regulation domain at the N-terminus
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
40
-
half-life: 3.5 min
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, pH 8.0, 1 mM EDTA, 0.05% Triton X-100, 0.5 mM dithiothreitol, 10 mM KCl, 3 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
117fold
-
purification of recombinant enzyme
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
recombinant production of APE1
-
repression of APE/Ref-1 by an antisense overexpression, transfection of mouse B-cells with phosphorothioate oligonucleotide, which is complementary to the APE/Ref-1 mRNA sequence and overlaps the translation initiation site (antisense oligonucleotide)
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine