Information on EC 4.2.99.18 - DNA-(apurinic or apyrimidinic site) lyase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY
4.2.99.18
-
RECOMMENDED NAME
GeneOntology No.
DNA-(apurinic or apyrimidinic site) lyase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
the C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate
show the reaction diagram
mechanism
-
the C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate
show the reaction diagram
mechanism
-
the C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate
show the reaction diagram
mechanism
-
the C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate
show the reaction diagram
mechanism
-
the C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate
show the reaction diagram
T4 endonuclease V (EC 3.1.25.1) possesses both pyrimidine dimer DNA glycosylase activity and apurinic/apyrimidinic DNA endonuclease (EC 4.2.99.18) activity in a single polypeptide chain
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
beta-elimination
-
-
beta-elimination
-
-
beta-elimination
-
-
beta-elimination
-
-
beta-elimination
-
-
endonuclease activity
-
-
endonuclease activity
-
-
endonuclease activity
Escherichia coli BW565DE3
-
-
-
endonuclease reaction
-
-
endonuclease reaction
-
-
endonuclease reaction
-
-
endonuclease reaction
-
-
endonuclease reaction
-
-
endonuclease reaction
-
-
endonuclease reaction
-
-
endonuclease reaction
-
-
endonuclease reaction
-
-
endonuclease reaction
-
-
endonuclease reaction
-
-
endonuclease reaction
-
APE1 has dual activities, a strong endonuclease activity, and a weak exonuclease-phosphodiesterase activity
endonuclease reaction
-
the protein has AP endonuclease and 3'-5' exonuclease activity
endonuclease reaction
-
an essential protein that functions as part of base excision repair to remove mutagenic and cytotoxic abasic sites from DNA
endonuclease reaction
-
associative one-step hydrolytic mechanism
endonuclease reaction
-
cleavage of the phosphodiester either 5' or 3' to an apurinic/apyrimidinic site
exonuclease reaction
-
-
hydrolysis
-
-
phospho-group transfer
-
-
lyase rather than hydrolase reaction
-
-
additional information
-
APE1 possesses endonuclease, exonuclease and phosphodiesterase activity
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.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8-oxoG DNA glycosylase
O29876
-
abasic (AP)-endonuclease
P23196
-
abasic (AP)-endonuclease
-
-
abasic endonuclease
-
-
AdAPE1/Ref-1
-
-
Af0371
O29876
gene name
Afogg enzyme
O29876
bifunctional enzyme with both DNA glycosylase and apurinic/apyrimidinic lyase activities
AP 1
-
-
-
-
AP DNA endonuclease 1
-
-
AP Dnase
-
-
-
-
AP endo
-
-
-
-
AP endo
-
-
AP endonuclease
-
-
-
-
AP endonuclease
-
-
AP endonuclease
O29675
exonuclease III (ExoIII)
AP endonuclease
-
-
AP endonuclease
Bacillus subtilis PS832
-
-
-
AP endonuclease
-
-
AP endonuclease
P27695
-
AP endonuclease
-
-
AP endonuclease
-
-
AP endonuclease
O15922
-
AP endonuclease
-
-
AP endonuclease
Q8U437
-
AP endonuclease
-
-
AP endonuclease 1
-
-
AP endonuclease 1
-
-
AP endonuclease 1
-
-
AP endonuclease 1
-
-
AP endonuclease 1
Trypanosoma brucei 449
-
-
-
AP endonuclease Ape1
-
-
AP endonuclease Class I
-
-
-
-
AP endonuclease I
-
-
AP lyase
-
-
-
-
AP lyase
-
-
AP lyase
-
-
AP site-DNA 5'-phosphomonoester-lyase
-
-
AP-endonuclease
-
-
-
-
AP-endonuclease
-
-
AP-endonuclease
-
-
AP-endonuclease 1
-
-
AP-endonuclease 1
-
-
AP-endonuclease 1
T1SGV2
-
AP-endonuclease 1
T1SGV2
-
-
AP-endonuclease 2
T1SHD4
-
AP-endonuclease 2
T1SHD4
-
-
AP-lyase
-
-
Ap1
T1SGV2
-
Ap1
T1SGV2
-
-
Ap2
T1SHD4
-
Ap2
T1SHD4
-
-
Ape
-
-
-
-
Ape
P23196
-
APE-1
P27695
-
APE/Ref-1
-
-
APE/Ref-1
-
-
APE1
P23196
-
APE1
Escherichia coli BW565DE3
-
-
-
APE1
-
also known as APEX, HAP1 and Ref1
APE1
-
APE1 belongs to the class II apurinic/apyrimidinic endonucleases
APE1
P28352
-
APE1/Ref-1
P27695
-
APE1/Ref-1
-
-
Ape2
-
-
APEN
-
-
-
-
APEX nuclease
-
-
-
-
APEX1
-
-
APN
F6KAZ5
-
APN1
-
-
-
-
APN1
F6KAZ5
-
apurinic DNA endonuclease
-
-
-
-
apurinic endodeoxyribonuclease
-
-
-
-
apurinic endonuclease
-
-
-
-
apurinic endonuclease
-
-
apurinic endonuclease 1
-
-
apurinic endonuclease 1
-
also known as Ref-1 or HAP1
apurinic-apyrimidinic DNA endonuclease
-
-
-
-
apurinic-apyrimidinic endodeoxyribonuclease
-
-
-
-
apurinic-apyrimidinic endonuclease
-
-
-
-
apurinic-apyrimidinic endonuclease
-
-
apurinic-apyrimidinic endonuclease 1
-
-
apurinic-apyrimidinic endonuclease I
-
-
apurinic-apyrimidinic endonuclease I
-
-
apurinic/apyrimidic endonuclease 1
-
member of the divalent cation-dependent phosphoesterase superfamily of proteins
apurinic/Apyrimidinic (AP) endonuclease 1
-
-
apurinic/apyrimidinic AP endonuclease
-
-
apurinic/apyrimidinic DNA endonuclease 1
-
-
apurinic/apyrimidinic endonuclease
-
-
apurinic/apyrimidinic endonuclease
O29675
-
apurinic/apyrimidinic endonuclease
-
-
apurinic/apyrimidinic endonuclease
Bacillus subtilis PS832
-
-
-
apurinic/apyrimidinic endonuclease
-
-
apurinic/apyrimidinic endonuclease
-
-
apurinic/apyrimidinic endonuclease
-
-
apurinic/apyrimidinic endonuclease
P27695
-
apurinic/apyrimidinic endonuclease
-
-
apurinic/apyrimidinic endonuclease
-
-
apurinic/apyrimidinic endonuclease
O15922
-
apurinic/apyrimidinic endonuclease
-
-
apurinic/apyrimidinic endonuclease
Q8U437
-
apurinic/apyrimidinic endonuclease
-
-
apurinic/apyrimidinic endonuclease
P22936
-
apurinic/apyrimidinic endonuclease
Q9AIV4
-
apurinic/apyrimidinic endonuclease
Q9AIV4
-
-
apurinic/apyrimidinic endonuclease
-
-
apurinic/apyrimidinic endonuclease 1
-
-
apurinic/apyrimidinic endonuclease 1
-
-
apurinic/apyrimidinic endonuclease 1/redox factor-1
-
-
apurinic/apyrimidinic endonuclease APE1
-
-
apurinic/apyrimidinic endonuclease-1
-
-
apurinic/apyrimidinic endonuclease-1
P27695
-
apurinic/apyrimidinic endonuclease-1/Redox factor-1
-
multifunctional DNA base excision repair and redox regulation enzyme
apurinic/apyrimidinic endonuclease/redox effector factor-1
-
-
apurinic/apyrimidinic endonuclease/redox effector factor-1
-
-
Apurinic/apyrimidinic endonuclease1/redox factor 1
-
-
apurinic/apyrimidinic endonuclease1/redox factor-1
-
-
apurinic/apyrimidinic lyase
-
-
-
-
apurinic/apyrimidinic lyase
-
catalytic subunit of the HSV-1 DNA polymerase (Pol) (UL30) (EC 2.7.7.7) exhibits apurinic/apyrimidinic and 5'-deoxyribose phosphate lyase activities
apurinic/apyrimidinic site lyase
-
-
apurinic/apyrimidinic specific endonuclease
-
-
-
-
apyrimidinic endonuclease
-
-
-
-
archaeal GO glycosylase
Q8ZVK6
-
archaeal GO glycosylase
Pyrobaculum aerophilum DSM 7523
Q8ZVK6
-
-
BAP1
-
-
class II AP endonuclease LMAP
-
homolog of human Ape1
class II apurinic/apyrimidinic(AP)-endonuclease
-
-
-
-
deoxyribonuclease (apurinic or apyrimidinic)
-
-
-
-
DNA lyase
-
-
DNA polymerase X
-
-
DNA-(apurinic or apyrimidinic site) lyase
-
-
DNA-(apurinic or apyrimidinic site) lyase
-
-
DNA-(apurinic or apyrimidinic site) lyase
-
-
DNA-(apurinic or apyrimidinic site) lyase
-
-
DNA-(apurinic or apyrimidinic site) lyase
-
-
E. coli endonuclease III
-
-
-
-
EC 3.1.25.2
-
-
formerly
-
EcoNth
-
a bifunctional enzyme that has DNA glycosylase and apurinic/apyrimidinic lyase activity
Endo III
-
-
Endodeoxyribonuclease
-
-
-
-
endodeoxyribonuclease III
-
-
-
-
endonuclease III
-
-
-
-
endonuclease III
-
-
endonuclease III
-
-
endonuclease III
-
-
endonuclease IV
-
an abasic or apurinic-apyrimidinic endonuclease superfamily crucial for DNA base excision repair
endonuclease IV
Escherichia coli BW565DE3
-
an abasic or apurinic-apyrimidinic endonuclease superfamily crucial for DNA base excision repair
-
endonuclease VI
-
-
-
-
endonuclease VIII
P50465
-
Escherichia coli endonuclease III
-
-
-
-
HAP1
-
-
-
-
HAP1
-
-
HAP1
P27695
-
HAP1h
-
-
-
-
hNTH
-
-
hNTH1
-
-
hOgg1 protein
-
-
human apurinic/apyrimidinic endonuclease
-
-
human apurinic/apyrimidinic endonuclease 1
-
-
Kae1
-
kinase-associated endopeptidase 1 exibits a class I apurinic endonuclease activity, no activity in vitro
KsgA
-
a 16S rRNA adenine methyltransferase with DNA glycosylase/AP lyase activity
KsgA
Escherichia coli KSR7
-
a 16S rRNA adenine methyltransferase with DNA glycosylase/AP lyase activity
-
Micrococcus luteus UV endonuclease
-
-
-
-
MJ0724
Q58134
locus name
MjaOgg2
Q58134
bifunctional enzyme that catalyzes the excision of 8-oxoguanine by cleaving the N-glycosylic bond between the base and the deoxyribose moiety (glycosylase activity) and subsequently cleave the DNA backbone (lyase activity)
mtAPE
P23196
mtAPE is derived from APE1 after deletion of 33N-terminal residues
multi-functional apyrimidinic endonuclease1/redox factor-1
-
-
N-glycosylase AP lyase
-
-
N-glycosylase apurinic/apyrimidinic lyase
-
-
NapE
-
Neisserial AP endonuclease
Nei
P50465
-
Nfo
-
-
-
-
Nfo
Bacillus subtilis PS832
-
-
-
Ntg1p
-
-
-
-
Ntg2p
-
-
-
-
NTH1
-
-
-
-
nuclease SmnA
-
-
nuclease, apurinic endodeoxyribo-
-
-
-
-
nuclease, apurinic-apyrimidinic endodeoxyribo-
-
-
-
-
nuclease, endodeoxyribo-, III
-
-
-
-
Ogg2
Q97ZK2
bifunctional enzyme that catalyzes the excision of 8-oxoguanine by cleaving the N-glycosylic bond between the base and the deoxyribose moiety (glycosylase activity) and subsequently cleave the DNA backbone (lyase activity)
Ogg2
Q97ZK2
bifunctional enzyme that catalyzes the excision of 8-oxoguanine by cleaving the N-glycosylic bond between the base and the deoxyribose moiety (glycosylase activity) and subsequently cleave the DNA backbone (lyase activity)
-
oxoG DNA glycosylase
Q58134
-
Pa-AGOG
Q8ZVK6
bifunctional enzyme that catalyzes the excision of 8-oxoguanine by cleaving the N-glycosylic bond between the base and the deoxyribose moiety (glycosylase activity) and subsequently cleave the DNA backbone (lyase activity, EC 4.2.99.18)
Pa-AGOG
Pyrobaculum aerophilum DSM 7523
Q8ZVK6
bifunctional enzyme that catalyzes the excision of 8-oxoguanine by cleaving the N-glycosylic bond between the base and the deoxyribose moiety (glycosylase activity) and subsequently cleave the DNA backbone (lyase activity, EC 4.2.99.18)
-
Pa-AGOG DNA glycosylase
Q8ZVK6
bifunctional enzyme that catalyzes the excision of 8-oxoguanine by cleaving the N-glycosylic bond between the base and the deoxyribose moiety (glycosylase activity) and subsequently cleave the DNA backbone (lyase activity)
Pa-AGOG DNA glycosylase
Pyrobaculum aerophilum DSM 7523
Q8ZVK6
bifunctional enzyme that catalyzes the excision of 8-oxoguanine by cleaving the N-glycosylic bond between the base and the deoxyribose moiety (glycosylase activity) and subsequently cleave the DNA backbone (lyase activity); bifunctional enzyme that catalyzes the excision of 8-oxoguanine by cleaving the N-glycosylic bond between the base and the deoxyribose moiety (glycosylase activity) and subsequently cleave the DNA backbone (lyase activity)
-
PAE2237
Q8ZVK6
locus name
PAE2237
Pyrobaculum aerophilum DSM 7523
Q8ZVK6
locus name
-
PALF
-
PNK and APTX-like FHA protein
pE296R
-
African swine fever virus, ASFV, protein pE296R, predicted to be a class II apurinic/apyrimidinic endonuclease
PF0258
Q8U437
the PF0258 protein exhibited AP endonuclease activity
phage-T4 UV endonuclease
-
-
-
-
redox factor-1
-
-
redox factor-1:Ref-1
-
-
REF-1 protein
-
-
-
-
Ref1
-
-
-
-
Ref1
-
-
Smx nuclease
Q9AIV4
-
Smx nuclease
Q9AIV4
-
-
SSO0904
Q97ZK2
locus name
SSO0904
Q97ZK2
locus name
-
UV endo V
-
-
-
-
UV endonuclease
-
-
-
-
UV endonuclease V
-
-
-
-
X-ray endonuclease III
-
-
ZAP1
-
-
zApe
-
-
MMH
-
-
-
-
additional information
-
nomenclature of AP endonucleases and AP lyases
additional information
-
Ku is a NHEJ factors with effective 5'-deoxyribose-5-phosphate lyase/apurinic/apyrimidinic site lyase activities
CAS REGISTRY NUMBER
COMMENTARY
60184-90-9
-
61811-29-8
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
the swine macrophage is the host cell of the virus
-
-
Manually annotated by BRENDA team
strain 168 (wild-type) and strain PS832 (trp+ revertant of strain 168), prototrophic derivative
-
-
Manually annotated by BRENDA team
strain PS832
-
-
Manually annotated by BRENDA team
Bacillus subtilis PS832
strain PS832
-
-
Manually annotated by BRENDA team
zebrafish
-
-
Manually annotated by BRENDA team
endonuclease V
-
-
Manually annotated by BRENDA team
Escherichia coli infected with bacteriophage T4, T4 endonuclease V (EC 3.1.25.1) possesses both pyrimidine dimer DNA glycosylase activity and apurinic/apyrimidinic DNA endonuclease (E.C. 3.1.25.2) activity in a single polypeptide chain
-
-
Manually annotated by BRENDA team
bacteriophage T4 infected, T4 endonuclease V (EC 3.1.25.1) possesses both pyrimidine dimer DNA glycosylase activity and apurinic/apyrimidinic DNA endonuclease (EC 4.2.99.18) activity in a single polypeptide chain
-
-
Manually annotated by BRENDA team
endonuclease III; enzyme also has DNA N-glycosylase activity
-
-
Manually annotated by BRENDA team
endonuclease VI
-
-
Manually annotated by BRENDA team
enzyme also has DNA N-glycosylase activity; X-ray endonuclease III
-
-
Manually annotated by BRENDA team
strain BW565DE3
-
-
Manually annotated by BRENDA team
strain KSR7
-
-
Manually annotated by BRENDA team
Escherichia coli BW565DE3
strain BW565DE3
-
-
Manually annotated by BRENDA team
Escherichia coli KSR7
strain KSR7
-
-
Manually annotated by BRENDA team
endonuclease A
-
-
Manually annotated by BRENDA team
expressed in fibroblasts of Mus musculus
-
-
Manually annotated by BRENDA team
human sequence
SwissProt
Manually annotated by BRENDA team
recombinant
UniProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
enzyme forms A and B
-
-
Manually annotated by BRENDA team
male nude mice, BALB/c nu/nu 5-6 weeks old
-
-
Manually annotated by BRENDA team
mice deficient in methionine adenosyltransferase 1a have chronic hepatic deficiency of S-adenosylmethionine and increased oxidative stress, and develop hepatocellular carcinoma
-
-
Manually annotated by BRENDA team
Pyrobaculum aerophilum DSM 7523
-
SwissProt
Manually annotated by BRENDA team
3 enzyme forms: APcI, APcII, APcIII
-
-
Manually annotated by BRENDA team
female Sprague-Dawley rats with spinal cord injury
-
-
Manually annotated by BRENDA team
Sprague-Dawley rat
-
-
Manually annotated by BRENDA team
strain D273-10B/A1
-
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae D273-10B/A1
strain D273-10B/A1
-
-
Manually annotated by BRENDA team
identification of a new 5' exon, exon 1, in the apn1 gene. The inactivity of Schizosaccharomyces pombe Apn1 is due to a nonsense mutation in the fifth codon of this exon. Reversion of this mutation restores the AP endonuclease activity of Apn1. The apn1 nonsense mutation is only found in laboratory strains derived from L972 h- and not in unrelated isolates of Schizosaccharomyces pombe. Since all Schizosaccharomyces pombe laboratory strains originate from L972 h-, it appears that all experiments involving Schizosaccharomyces pombe have been conducted in an apn1- mutant strain with a corresponding DNA repair deficiency
SwissProt
Manually annotated by BRENDA team
strain GS-5
SwissProt
Manually annotated by BRENDA team
strain UA159 and UR100, activity is present at greater levels in cells grown at low pH than grown at pH 7
-
-
Manually annotated by BRENDA team
strain GS-5
SwissProt
Manually annotated by BRENDA team
strain UA159 and UR100, activity is present at greater levels in cells grown at low pH than grown at pH 7
-
-
Manually annotated by BRENDA team
Trypanosoma brucei 449
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
APE1 knockdown abrogates neuroprotection against cerebral ischemia
malfunction
-
knockdown of ZAP1 levels does not alter base excision repair in early embryogenesis
malfunction
-
knocking down Ape1/Ref-1 expression enhances estrogen responsiveness of the progesterone receptor and pS2 genes but does not alter the expression of the constitutively active 36B4 gene
malfunction
-
short hairpin RNA-mediated stable suppression of APE-1 results in increased apoptosis in gastric epithelial cells after Helicobacter pylori infection
malfunction
-
siRNA knockdown of endogenous APE1 impairs high-mobility group box 1-mediated cytokine expression and MAPK activation in THP-1 cells
physiological function
Q8U437
AP endonuclease and proliferating cell nuclear antigen form a functional complex to generate a gap of several nucleotides for efficient DNA repair synthesis
physiological function
-
AP endonuclease pE296R is essential for virus growth in swine macrophages. DNA repair functions of pE296R are AP endonucleolytic, 3'-5' exonuclease, 3-diesterase and nucleotide incision repair activities
physiological function
-
APE1 functions as a critical rate-limiting enzyme in DNA base excision repair and accounts for nearly all of the AP site incision activities in cell extracts, APE1 also exerts unique redox activity to regulate the DNA-binding affinity of certain transcriptional factors by controlling the redox status of their DNA-binding domain
physiological function
-
APE1 has a central role in the coordination of base excision repair
physiological function
-
APE1 is a dual regulator of inflammatory signaling to high-mobility group box 1 by human monocytes/macrophages. Forced cytoplasmic overexpression of APE1 profoundly attenuates the upregulation of high-mobility group box 1-mediated reactive oxygen species generation, cytokine secretion, and cyclooxygenase-2 expression by primary monocytes and macrophage-like THP-1 cell lines, the extracellular release of high-mobility group box 1 by activated macrophages is inhibited by APE1 transfection
physiological function
-
APE1 is a key multifunctional protein involved in DNA base excision repair
physiological function
-
APE1 is a key upstream regulator in TLR2-dependent keratinocyte inflammatory responses
physiological function
-
APE1 is a multifunctional enzyme that plays a central role in base excision repair of DNA and is also involved in the alternative nucleotide incision repair pathway
physiological function
-
APE1 is required for pituitary adenylate cyclase-activating polypeptide-induced neuroprotection against global cerebral ischemia
physiological function
-
APE1 is the major nuclease for excising abasic sites and particular 3'-obstructive termini from DNA, and is an integral participant in the base excision repair pathway
physiological function
-
APE1 regulates c-myc mRNA level possibly via its endoribonuclease activity
physiological function
-
APE1 stimulates the multiple-turnover excision of hypoxanthine by alkyladenine DNA glycosylase but has no effect on single-turnover excision
physiological function
-
Ape1/Ref-1 enhances the interaction of estrogen receptor alpha with estrogen-response elements in DNA, Ape1/Ref-1 alters expression of the endogenous, estrogen-responsive progesterone receptor and pS2 genes in MCF-7 cells and associates with estrogen-response elements-containing regions of these genes in native chromatin
physiological function
-
both DNA repair and acetylation functions of APE-1 modulate programmed cell death, the DNA repair activity of APE-1 inhibits the mitochondrial pathway, whereas the acetylation function inhibits the extrinsic pathway during Helicobacter pylori infection
physiological function
-
in addition to the apurinic/apyrimidinic DNA endonuclease activity, APE1 has 3'-5' DNA exonuclease, 3' phosphodiesterase, and RNase H activities
physiological function
-
in addition to the apurinic/apyrimidinic DNA endonuclease activity, APE1 has 3'-5' DNA exonuclease, 3'-phosphodiesterase, and RNase H activities
physiological function
-
nuclear factor -kappaB is activated by cytoplasmic, but not nuclear, Ape1 to cause Cox-2 expression. Ape1 can enhance lung tumor malignancy through nuckear factor-kappaB activation
physiological function
-
overexpression of Nfo about 50fold in spores increases the wet heat resistance of exoA nfo Bacillus subtilis spores that lack most alpha/beta-type small, acid-soluble spore proteins, but has no effect on these spores' UV-C resistance. Nfo overexpression also increases these spores' dry heat resistance, and to levels slightly greater than that of wild type spores
physiological function
-
mice deficient for the base excision repair enzyme, apurinic/apyrimidinic endonuclease APE2 protein develop relatively normally, but they display defects in lymphopoiesis. Mice nullizygous for APE2 show an inhibition of the pro-B to pre-B cell transition. APE2 is not required for V(D)J recombination and the turnover rate of APE2-deficient progenitor B cells is nearly normal. The production rate of pro- and pre-B cells is reduced due to a p53-dependent DNA damage response. Progenitors from APE2-deficient mice differentiate normally in response to IL-7 in in vitro stromal cell cocultures, but pro-B cells show defective expansion. APE2-deficient mice show a delay in recovery of B lymphocyte progenitors following bone marrow depletion by 5-fluorouracil, with the pro-B and pre-B cell pools still markedly decreased 2 weeks after a single treatment
physiological function
F6KAZ5
over-expression of APN in Toxoplasma gondii confers protection from DNA damage, and viable knockouts of APN are not obtainable. An inducible APN knockdown mutant demonstrates that APN is critical for Toxoplasma to recover from DNA damage
physiological function
-
overexpression of APE/Ref-1 using adenovirus and restoration of APE small peptides significantly reduces kainic acid-induced hippocampal cell death. Both silencing of APE/Ref-1 by siRNA and inhibition of endonuclease by an antibody significantly increase caspase-3 activity and apoptotic cell death triggered from the early time after exposure to kainic acid. Findings suggest that cell death is initiated by reducing APE/Ref-1 protein and inhibiting its repair function in spite of enough protein amounts
physiological function
-
spores lacking both AP endonucleases Nfo and ExoA and major alpha/beta-type small acid-soluble spore proteins are significantly more sensitive to 254-nm UVC, environmental UV >280 nm, X-ray exposure, and high-energy charged particle bombardment and have elevated mutation frequencies compared to those of wild-type spores and spores lacking only one or both AP endonucleases or major alpha/beta-type small acid-soluble spore proteins
physiological function
-
the enzyme is part of the base excision repair (BER) pathway. It protects from oxidative damage by removing the major product of DNA oxidation, 8-oxoguanine, from single- and double-stranded DNA substrates. Bifunctional enzyme that catalyzes the excision of 8-oxoguanine by cleaving the N-glycosylic bond between the base and the deoxyribose moiety (glycosylase activity) and subsequently cleave the DNA backbone (lyase activity, EC 4.2.99.18)
physiological function
-
isoform Ape1 is an essential factor stabilizing telomeric DNA, and its deficiency is associated with telomere dysfunction and segregation defects in immortalized cells maintaining telomeres by either the alternative lengthening of telomeres pathway or telomerase expression or in normal human fibroblasts
physiological function
-
isoform APE1-deficient cell lines derived from bloodstream stage trypanosomes, confirm that the AP endonuclease is not essential for viability in this cell type under in vitro culture conditions. An inverse correlation exists between the level of AP endonuclease in the cell and the number of endogenously generated abasic sites in its genomic DNA. Depletion of APE1 renders cells hypersensitive to AP site and strand break-inducing agents such as methotrexate and phleomycin, respectively, but not to alkylating agents. The increased susceptibility of APE1-depleted cells to nitric oxide suggests an essential role in protection against the immune defenses of the mammalian host
physiological function
T1SGV2, T1SHD4
overexpression of isoform AP1 increases epimastigotes viability when they are exposed to acute ROS/RNS attack. This protective effect is more evident when parasites are submitted to persistent reactive oxygen species/reactive nitrogen species exposition
physiological function
-
overexpression of isoform AP1 increases epimastigotes viability when they are exposed to acute ROS/RNS attack. This protective effect is more evident when parasites are submitted to persistent reactive oxygen species/reactive nitrogen species exposition
-
physiological function
Bacillus subtilis PS832
-
overexpression of Nfo about 50fold in spores increases the wet heat resistance of exoA nfo Bacillus subtilis spores that lack most alpha/beta-type small, acid-soluble spore proteins, but has no effect on these spores' UV-C resistance. Nfo overexpression also increases these spores' dry heat resistance, and to levels slightly greater than that of wild type spores
-
physiological function
Pyrobaculum aerophilum DSM 7523
-
the enzyme is part of the base excision repair (BER) pathway. It protects from oxidative damage by removing the major product of DNA oxidation, 8-oxoguanine, from single- and double-stranded DNA substrates. Bifunctional enzyme that catalyzes the excision of 8-oxoguanine by cleaving the N-glycosylic bond between the base and the deoxyribose moiety (glycosylase activity) and subsequently cleave the DNA backbone (lyase activity, EC 4.2.99.18)
-
physiological function
Trypanosoma brucei 449
-
isoform APE1-deficient cell lines derived from bloodstream stage trypanosomes, confirm that the AP endonuclease is not essential for viability in this cell type under in vitro culture conditions. An inverse correlation exists between the level of AP endonuclease in the cell and the number of endogenously generated abasic sites in its genomic DNA. Depletion of APE1 renders cells hypersensitive to AP site and strand break-inducing agents such as methotrexate and phleomycin, respectively, but not to alkylating agents. The increased susceptibility of APE1-depleted cells to nitric oxide suggests an essential role in protection against the immune defenses of the mammalian host
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(pT)7(p(2,3-dihydroxy-5-oxopentyl phosphate))(pT)6
?
show the reaction diagram
-
-
-
-
?
12-mer oligodeoxyribonucleotide containing a 2'-deoxyguanosine at the natural AP site
?
show the reaction diagram
-
-
-
-
-
12-mer oligodeoxyribonucleotide containing a natural AP site
?
show the reaction diagram
-
the minimal kinetic model for the natural AP site incision consists of four stages corresponding to three different transient states of APE1. When the enzyme is complexed with the AP-substrate, the catalytic cycle is completed within 3 s
-
-
?
12-mer oligodeoxyribonucleotide containing a tetrahydrofuran analogue at the natural AP site
?
show the reaction diagram
-
-
-
-
-
18-mer containing P33-labeled tetrahydrofuran
?
show the reaction diagram
-
-
-
-
?
21 bp double-stranded DNA containing an apurinic/apyrimidinic-site analogue
?
show the reaction diagram
Q5KX27
-
the affinity of EndoIV for the substrate analogue is very high and its dissociation constant is less than 0.01 microM. A C-terminal DNA-recognition loop at residues 265-269 that is only present in the long type enzymes contributes to its high affinity for apurinic/apyrimidinic sites
-
?
26-bp-oligonucleotide
5'-hexachloro-fluorescein phosphoramidite-labeled 13-mer fragment + ?
show the reaction diagram
F6KAZ5
oligonucleotide containing a 5'-hexachloro-fluorescein phosphoramidite-labeled tetrahydrofuranyl residue in the middle
-
-
?
30-mer oligonucleotide duplex DNa containing a tetrahydrofuran analogue
?
show the reaction diagram
-
-
-
-
?
34-mer dsDNA containing an internal tetrahydrofuran
18-mer ds DNA + ?
show the reaction diagram
-
-
-
-
?
34-mer ssDNA containing an internal tetrahydrofuran
18-mer ssDNA + ?
show the reaction diagram
-
-
-
-
-
34FDNA
?
show the reaction diagram
-
-
-
-
?
34FRNA
?
show the reaction diagram
-
-
-
-
?
35 base pair oligonucleotide containing 5,6-dihydrouracil opposite A
?
show the reaction diagram
-
-
-
-
?
35 base pair oligonucleotide containing 5,6-dihydrouracil opposite G
?
show the reaction diagram
-
-
-
-
?
35 base pair oligonucleotide containing 5,6-dihydroxy-5,6-dihydrothymine opposite A
?
show the reaction diagram
-
-
-
-
?
35 base pair oligonucleotide containing 5,6-dihydroxy-5,6-dihydrothymine opposite G
?
show the reaction diagram
-
-
-
-
?
37mer with AP/A
?
show the reaction diagram
-
-
-
-
-
37mer with AP/C
?
show the reaction diagram
-
-
-
-
-
37mer with AP/G
?
show the reaction diagram
-
-
-
-
-
37mer with AP/T
?
show the reaction diagram
-
-
-
-
-
37mer with dihydrouridine
?
show the reaction diagram
-
-
-
-
-
43-mer oligonucleotide containing apurinic/apyrimidinic sites
fragments of DNA
show the reaction diagram
-
-
-
-
?
43-mer oligonucleotide containing the AP-site analog tetrahydrofuran at nt 31
?
show the reaction diagram
-
-
-
-
?
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
?
show the reaction diagram
P50465
-
-
-
?
5'-CTCTCCCTTC-8-oxo-7,8-dihydroguanine-CTCCTTTCCTCT-3'
?
show the reaction diagram
P50465
-
-
-
?
5'-Cy3-CAAGGTAGTrUATCCTTG-1-Black Hole Quencher1-3'
?
show the reaction diagram
-
the fluorogenic substrate OligoI is based on the sequence immediately surrounding the stem V-loop region (OligoI) and incorporating a fluorescent tag, Cy3, at the 5' end and a fluorescence Black Hole Quencher at the 3' end of the oligonucleotide
-
-
?
5'-Cy3-CAAGGTAGTTATCCTTG-1-Black Hole Quencher1-3'
?
show the reaction diagram
-
the fluorogenic substrate DNAOligoI is based on the sequence immediately surrounding the stem Vloop region (OligoI) and incorporating a fluorescent tag, Cy3, at the 5' end and a fluorescence Black Hole Quencher at the 3' end of the oligonucleotide, DNAOligoI has an identical sequence to OligoI except that deoxythymidylate is substituted for 2' hydroxyl uridine
-
-
?
5'-GACAAGCGCAG-(5R,6S)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
?
show the reaction diagram
P50465
-
-
-
?
5'-GACAAGCGCAG-(5S,6R)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
?
show the reaction diagram
P50465
-
-
-
?
5'-TCGAGGATCCTGAGCTCGAGTCGACGXTCGCGAATTCTGCGGATCCAAGC-3'
?
show the reaction diagram
-
a synthetic stable AP-site analog where X represents tetrahydrofuran
-
-
?
5'-TCGAGGATCCTGAGCTCGAGTCGACGXTCGCGAATTCTGCGGATCCAAGC-3'
?
show the reaction diagram
P28352
a synthetic stable AP-site analog where X represents tetrahydrofuran
-
-
?
AP DNA
fragments of DNA
show the reaction diagram
-
AP sites
-
-
?
AP-DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
AP-DNA
fragments of DNA
show the reaction diagram
P27695
Base excision repair pathway, enzyme cleaves the 5'-phosphodiester bond, generating 3'-OH and 5'-dRP termini
-
-
?
AP-DNA
fragments of DNA
show the reaction diagram
Escherichia coli BW565DE3
-
-
-
-
?
AP-DNA-DNA
?
show the reaction diagram
-
synthetic DNA-DNA hybrid
-
-
?
AP-DNA-RNA
?
show the reaction diagram
-
synthetic DNA-RNA hybrids that simulate a transcription intermediate
-
-
?
c-myc coding region determinant mRNA
?
show the reaction diagram
-
APE1 preferentially cleaves in between UA and CA dinucleotides of c-myc coding region determinant RNA
-
-
?
c-myc RNA
?
show the reaction diagram
-
APE1 cleaves at the UA, CA, and UG sites of c-myc RNA in vitro
-
-
?
CAAXACCTTCATCCTTTCC
?
show the reaction diagram
-
X: AP site
-
-
?
CAXAACCTTCATCCTTTCC
?
show the reaction diagram
-
X: AP site
-
-
?
CTAGTCAXCACTGTCTGTGGATAC
?
show the reaction diagram
-
X: AP site
-
-
?
CXAAACCTTCATCCTTTCC
?
show the reaction diagram
-
X: AP site
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
P27695
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
O15527
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
P78549
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
Q9SIC4
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
O35980
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
Q8U437
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
cleavage of apyrimidinic DNA both 5' and 3' to the site of damage in a ratio of 60:40, respectively, even though it can cleave on both sides of an internal apyrimidinic site, it does not release deoxyribose 5-phosphate from terminal apyrimidinic sites
-
?
DNA
fragments of DNA
show the reaction diagram
-
cleaves all four types of abasic site-containing substrates: AP/G, AP/A, AP/C, AP/T, with a moderate preference for AP/T sites
-
?
DNA
fragments of DNA
show the reaction diagram
-
acts on specific adenines in single-stranded DNA
-
?
DNA
fragments of DNA
show the reaction diagram
-
cleaves single- and double-stranded oligonucleotides lacking one or two bases
-
?
DNA
fragments of DNA
show the reaction diagram
-
hydrolyzes phosphodiester bond near heat-induced apruinic sites in double or single strand DNA
-
?
DNA
fragments of DNA
show the reaction diagram
-
hydrolyzes phosphodiester bond near heat-induced apruinic sites in double or single strand DNA
-
?
DNA
fragments of DNA
show the reaction diagram
O15527
enzyme reveals glycosylase activity and apurinic/apyrimidinic lyase activity on duplex DNA containing 8-OH-G, DNA containing 8-OH-G/A is not cleaved, DNA containing 8-OH-G/T and 8-OH-G/G is slightly cleaved
-
?
DNA
fragments of DNA
show the reaction diagram
-
acts specifically on pyrimidine dimers, preferring those in double-stranded DNA to those in singes-stranded DNA, enzyme has glycosylase and apyrimidinic/apurinic endonuclease activity, cleaves 3' to the AP site generating a 3'-deoxyribose moiety and a 5'-phosphate
-
?
DNA
fragments of DNA
show the reaction diagram
-
at low concentrations the enzyme is specific for depurinated native DNA, at higher concentrations it degrades DNA in a non-specific manner
-
?
DNA
fragments of DNA
show the reaction diagram
-
supercoiled DNA
-
?
DNA
fragments of DNA
show the reaction diagram
-
cleavage at abasic sites in duplexes with paired lesions is slower than in duplexes with single lesions. Double strand breaks are readily generated in duplexes with abasic sites positioned 3' to each other. In duplexes containing abasic sites set 1 base pair apart, 5' to each other, both enzymes slowly cleave the abasic site on one strand only and are unable to incise the other stand
-
?
DNA
fragments of DNA
show the reaction diagram
-
removes 5-hydroxy-2'-deoxycytidine and 5-hydroxy-2'-deoxyuridine via a N-glycosylase/beta-elimination reaction
-
?
DNA
fragments of DNA
show the reaction diagram
-
acts on both 5-hydroxycytosine and abasic sites, preferentially when these are situated opposite guanines
-
?
DNA
fragments of DNA
show the reaction diagram
-
cuts the DNA strands on the 5' side of the apurinic sites giving a 3'-OH and a 5'-phosphate
-
?
DNA
fragments of DNA
show the reaction diagram
-
cuts the DNA strands on the 5' side of the apurinic sites giving a 3'-OH and a 5'-phosphate
-
?
DNA
fragments of DNA
show the reaction diagram
-
catalyzes the hydrolysis of the 5'-phosphodiester bond at the abasic site
-
?
DNA
fragments of DNA
show the reaction diagram
-
catalyzes incision at the C4-keto-C-1-aldehyde site, hydrolyzes 3'-phosphoglycolates 25fold more slowly than C-4-keto-C-1-aldehydes
-
?
DNA
fragments of DNA
show the reaction diagram
-
recognizes and cleaves DNA substrates containing dihydrouracil, 2,6-diamino-4-hydroxy-5N-methylformamidopyrimidine and abasic sites, but not DNA substrates containing uracil or 8-oxoguanine
-
?
DNA
fragments of DNA
show the reaction diagram
-
endonucleolytic cleavage near apurinic or apyrimidinic sites to products with 5'-phosphates, e.g. UV-irradiated poly(dA)*poly(dT)
-
?
DNA
fragments of DNA
show the reaction diagram
-
cleaves the DNA phosphodiester backbone immediately 5' to an AP site, also shows 3'-phosphodiesterase activity, 3'-phosphatase activity, RNaseH and significant 3'-5'-exonuclease activity
-
?
DNA
fragments of DNA
show the reaction diagram
-
catalyzes phosphodiester bond cleavage via a lyase- rather than a hydrolase mechanism
-
?
DNA
fragments of DNA
show the reaction diagram
-
synthetic oligodeoxynucleotides containing abasic sites
-
?
DNA
fragments of DNA
show the reaction diagram
-
removes UV light and osmium tetroxide damaged bases via an N-glycosylase activity followed by a 3'-purinic/apyrimidinic endonuclease activity, product is a nucleoside-free site flanked by 3'- and 5'-terminal phosphate groups
-
?
DNA
fragments of DNA
show the reaction diagram
-
AP endonuclease I forms deoxyribose 3'-phosphate and 5'-OH termini upon cleaving depurinated DNA
-
?
DNA
fragments of DNA
show the reaction diagram
-
enzyme has a 3' to 5' exonuclease activity and shows additional functional similarities to DNA repair enzymes
-
?
DNA
fragments of DNA
show the reaction diagram
-
cleaves phosphodiester bridge wihich is the immediate neighbor of the AP site on its 5' side leaving 3'-OH and 5'-phosphate ends
-
?
DNA
fragments of DNA
show the reaction diagram
-
catalyzes 5'-incision of 2-deoxyribonolactone, but acts at least 10fold less effectively to remove the 3'-phosphates at direct strand breaks
-
?
DNA
fragments of DNA
show the reaction diagram
-
cleaves thymine glycol-containing form I plasmid DNA and a dihydrouracil-containing oligonucleotide duplex
-
?
DNA
fragments of DNA
show the reaction diagram
-
specific for apurinic sites
-
?
DNA
fragments of DNA
show the reaction diagram
-
specific for apurinic sites
-
?
DNA
fragments of DNA
show the reaction diagram
-
specific for apurinic sites
-
?
DNA
fragments of DNA
show the reaction diagram
-
specific for apurinic sites
-
?
DNA
fragments of DNA
show the reaction diagram
-
specific for apurinic sites
-
?
DNA
fragments of DNA
show the reaction diagram
-
specific for apurinic sites
-
?
DNA
fragments of DNA
show the reaction diagram
-
specific for apurinic sites
-
?
DNA
fragments of DNA
show the reaction diagram
-
specific for apurinic sites
-
?
DNA
fragments of DNA
show the reaction diagram
-
endonuclease III: excision of a number of thymine- and cytosine-derived lesions from DNA, no purine-derived lesions excised by endonuclease III
-
?
DNA
fragments of DNA
show the reaction diagram
-
endonucleolytic activity against apurinic and apyrimidinic sites and a dose-dependent response to DNA that has been X-irradiated, UV-irradiated or treated with OsO4
-
?
DNA
fragments of DNA
show the reaction diagram
-
cleaves the phosphodiester bond 3' to the apurinic/apyrimidinic site
-
?
DNA
fragments of DNA
show the reaction diagram
-
cleaves the phosphodiester bond 3' to the apurinic/apyrimidinic site
-
?
DNA
fragments of DNA
show the reaction diagram
-
cleaves the phosphodiester bond 3' to the apurinic/apyrimidinic site
-
?
DNA
fragments of DNA
show the reaction diagram
-
cleaves the phosphodiester bond 3' to the apurinic/apyrimidinic site
-
?
DNA
fragments of DNA
show the reaction diagram
-
enzyme recognizes apurinic and apyrimidinic sites induced by acid and gamma-rays, as well as lesions which are introduced into DNA by UV irradiation and OsO4
-
?
DNA
fragments of DNA
show the reaction diagram
-
duplex oligonucleotides containing the base lesion analogs O-methylhydoxylamine or O-benzylhydroxylamine, N-glycosylase activity generates intermediary AP site which is subsequently cleaved by the enzyme -associated AP lyase activity, O-alkoxyamine-modified AP sites are poorer substrates than the presumed physiological substrates
-
?
DNA
fragments of DNA
show the reaction diagram
-
dU)230 (ratio dT:dU is 15) partially depyrimidinated by uracil-DNA glycosylase
-
?
DNA
fragments of DNA
show the reaction diagram
-
enzyme generates only single-strand breaks when the base damage is set one and three base-pairs apart, and only slowly introduces double-strand breaks in substrates where base damage is set five or seven base-pairs apart. Treatment of an abasic site-containing DNA readily yields double-strand breaks.
-
?
DNA
fragments of DNA
show the reaction diagram
-
DNA containing dihydrouridine, 5,3-dihydrothymidine, 5-hydroxy-2'-deoxyuridine, 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine or tetrahydrofuranyl
-
?
DNA
fragments of DNA
show the reaction diagram
-
PM2 phage DNA
-
?
DNA
fragments of DNA
show the reaction diagram
Q9SIC4
exhibits DNA-glycosylase activity on different types of DNA substrates with pyrimidine damage, being able to release both urea and thymine glycol from double-stranded polydeoxyribonucleotides, also possesses an apurinic/apyrimidinic lyase activity on UV- or gamma-irradiated DNA substrates
-
?
DNA
fragments of DNA
show the reaction diagram
-
breaks strand on the 3'-side of apurinic sugar residues giving a 3'-OH and a 5'-phosphate
-
?
DNA
fragments of DNA
show the reaction diagram
-
alkylated-depurinated DNA
-
?
DNA
fragments of DNA
show the reaction diagram
-
rate of AP lyase-mediated strand cleavage is much slower than the rate of DNA N-glycoxsylase-mediated base release
-
?
DNA
fragments of DNA
show the reaction diagram
-
phage-T4 and Micrococcus luteus enzyme nick the C(3')-O-P-bond 3' to the apurinic/apyrimidinic sites in DNA, the phage enzyme can also subsequently nick the C(5')-O-P bond 5' to the apurinic/apyrimidinic site
-
?
DNA
fragments of DNA
show the reaction diagram
-
the beta-elimination reaction breaking the C3'-O-P bond 3' to an AP site can be followed by a delta-elimination reaction breaking the C5'-O-P bond 5' to the AP site, with the release of an unsaturated derivative of the base-free sugar and the generation of a gap flanked by 3'-phosphate and 5'-phosphate ends
-
?
DNA
fragments of DNA
show the reaction diagram
O35980
thymine glycol DNA glycosylase, urea DNA glycosylase and AP lyase activity
-
?
DNA
fragments of DNA
show the reaction diagram
-
recognizes urea, an oxidative ring fragmentation product of thymine
-
?
DNA
fragments of DNA
show the reaction diagram
-
no activity with methylated or OsO4-treated DNA
-
?
DNA
fragments of DNA
show the reaction diagram
-
when DNA containing thymine glycol is used as substrate the combined N-glycosylase/AP endonuclease activity is about 2fold higher than the AP endonuclease activity
-
?
DNA
fragments of DNA
show the reaction diagram
-
incises DNA damaged with UV light, ionizing radiation, OsO4, KMnO4 and H2O2 at cytosine and thymine sites
-
?
DNA
fragments of DNA
show the reaction diagram
-
specific for DNA containing either apurinic or apyrimidinic sites
-
?
DNA
fragments of DNA
show the reaction diagram
-
specific for DNA containing either apurinic or apyrimidinic sites
-
?
DNA
fragments of DNA
show the reaction diagram
-
specific for DNA containing either apurinic or apyrimidinic sites
-
?
DNA
fragments of DNA
show the reaction diagram
-
endonuclease A: activity for UV-irradiated DNA, gamma-irradiated DNA and OsO4-treated DNA
-
?
DNA
fragments of DNA
show the reaction diagram
-
base excision repair (BERa) pathway is initiated by lesion-specific glycosylases that excise the damaged base from the sugar-phosphate backbone, resulting in a potentially cytotoxic apurinic/apyrimidinic (AP) site intermediate that becomes the substrate for the major human AP endonuclease
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
bifunctional enzyme is involved in base excision repair, it is a bifunctional DNA glycosylase/apurinic/apyrimidinic lyase which removes hydrated, reduced, or oxidized bases from the DNA backbone as the initial step of base excision repair
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
DNA repair enzyme is involved in base excision repair of apurinic/apyrimidinic sites after oxidative DNA damage
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
DNA single-strand breaks containing 3'-blocking groups are generated from attack of the sugar backbone by reactive oxygen species or after base excision by DNA glycosylase, apurinic, apyrimidinic (AP) lyases
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
DNA single-strand breaks containing 3'-blocking groups are generated from attack of the sugar backbone by reactive oxygen species or after base excision by DNA glycosylase/apurinic/apyrimidinic (AP) lyases
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
enzyme plays an important role in oxidative signalling, transcription factor regulation, and cell cycle control
-
-
ir
DNA
fragments of DNA
show the reaction diagram
-
multifunctional enzyme involved in DNA base excision repair of oxidative DNA damage and in redox regulation of a number of transcription factors
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
oxidative DNA damage is primarily reversed by the base excision repair pathway, initiated by N-glycosylase apurinic/apyrimidinic lyase proteins
-
-
ir
DNA
fragments of DNA
show the reaction diagram
-
The latter lesions are processed by AP endonucleases, which are important components of the base excision repair pathway
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
5'-deoxyribose-5-phosphate and apurinic/apyrimidinic sites are excised with half-lives of 2.7 and 7.0 min, respectively
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
AP endonuclease pE296R has strong preference for mispaired and oxidative base lesions at the 3'-termini of single-strand breaks, the 3'-terminal damaged pyrimidines (uracil, 5,6-dihydrouracil, and 5-hydroxycytosine) are removed with higher efficiency than damaged purines inosine and 7,8-dihydro-8-oxoguanine
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
Ape1 cleaves the phosphodiester backbone 5' to the AP site generating 3'-hydroxyl and 5'-deoxyribosephosphate termini, Ape1 exhibits a prominent 5' hydrolytic AP endonuclease, a weak 3'-diesterase and a 3'-5'-exonuclease activity
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
KsgA has al DNA glycosylase/AP lyase activity for C mispaired with oxidized T
-
-
?
DNA
fragments of DNA
show the reaction diagram
Bacillus subtilis PS832
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
Saccharomyces cerevisiae D273-10B/A1
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
Escherichia coli KSR7
-
KsgA has al DNA glycosylase/AP lyase activity for C mispaired with oxidized T
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
enzyme has a 3' to 5' exonuclease activity and shows additional functional similarities to DNA repair enzymes, specific for apurinic sites
-
?
DNA containing 5-OH-C/A
?
show the reaction diagram
-
-
-
-
-
DNA containing 5-OH-C/G
?
show the reaction diagram
-
-
-
-
-
DNA containing an abasic site
?
show the reaction diagram
-
45-mer oligomer
-
-
?
DNA containing apurinic/apyrimidinic site
DNA fragments
show the reaction diagram
-
-
-
-
?
DNA containing apurinic/apyrimidinic sites
fragments of DNA
show the reaction diagram
-
specificity
-
-
?
DNA containing apurinic/apyrimidinic sites
fragments of DNA
show the reaction diagram
-
apurinic/apyrimidinic endonuclease Nfo protects Bacillus subtilis spores from DNA damage accumulated during spore dormancy
-
-
?
DNA containing apurinic/apyrimidinic sites
fragments of DNA
show the reaction diagram
-
C4'-oxidized abasic sites are efficiently excised via intermediate Schiff-base formation. Activity is 100fold less efficient than repair by exonuclease III
-
-
?
DNA containing apurinic/apyrimidinic sites
fragments of DNA
show the reaction diagram
-
hydrogen bonds to phosphate groups 3' to the cleavage site is essential for the binding of the enzyme to the product DNA, which may be necessary for efficient functioning of the base excision rapair pathway
-
-
?
DNA containing apurinic/apyrimidinic sites
fragments of DNA
show the reaction diagram
Q9AIV4
inducible enzyme, the enzyme exhibits endonucleolytic activity and is regulated as part of the acid-adaptive response of the organism. Smx is likely the primary, if not the sole, AP endonuclease induced during growth at low pH values, loss of Smx activity renders the mutant strain sensitive to hydrogen peroxide treatment but relatively unaffected by acid-mediated damage or near-UV irradiation
-
-
?
DNA containing apurinic/apyrimidinic sites
fragments of DNA
show the reaction diagram
-
endonuclease III plays an important cellular role by removing premutagenic pyrimidine damages produced by reactive oxygen species. EcoNth is a bifunctional enzyme that has DNA glycosylase and apurinic/apyrimidinic lyase activity
-
-
?
DNA containing apurinic/apyrimidinic sites
fragments of DNA
show the reaction diagram
-
the enzyme forms a Schiff base-type intermediate with the substrate after the damaged base is removed
-
-
?
DNA containing apurinic/apyrimidinic sites
fragments of DNA
show the reaction diagram
Q9AIV4
inducible enzyme, the enzyme exhibits endonucleolytic activity and is regulated as part of the acid-adaptive response of the organism. Smx is likely the primary, if not the sole, AP endonuclease induced during growth at low pH values, loss of Smx activity renders the mutant strain sensitive to hydrogen peroxide treatment but relatively unaffected by acid-mediated damage or near-UV irradiation
-
-
?
DNA containing dihydrouracil
?
show the reaction diagram
-
-
-
-
-
DNA containing tamdem dihydrouracil
?
show the reaction diagram
-
the human AP endonuclease APE1 can process the 3' termini generated by human endonuclease III (hNTH) and endonuclease VIII. Both human endonuclease III and endonuclease VIII cannot completely remove both dihydrouracil lesions. With the participation of APE1 and polynucleotide kinase, the 3'-lesions remaining in the products of the reaction with human endonuclease III and endonuclease VIII can efficiently removed. The resulting products can be utilized by repair DNA polymerases as primers for repair synthesis
-
-
?
DNA containing tandem dihydrouracil
?
show the reaction diagram
-
the human AP endonuclease APE1 can process the 3' termini generated by human endonuclease III (hNTH) and endonuclease VIII. Both human endonuclease III and endonuclease VIII cannot completely remove both dihydrouracil lesions. With the participation of APE1 and polynucleotide kinase, the 3'-lesions remaining in the products of the reaction with human endonuclease III and endonuclease VIII can efficiently removed. The resulting products can be utilized by repair DNA polymerases as primers for repair synthesis
-
-
?
DNA with 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine/C
?
show the reaction diagram
-
-
-
-
-
DNA with 2-deoxyribonolactone
?
show the reaction diagram
-
-
-
-
-
DNA with 5,6-dihydrothymidine/A
?
show the reaction diagram
-
-
-
-
-
DNA with 5,6-dihydrothymine
?
show the reaction diagram
-
-
-
-
-
DNA with 5,6-dihydrouracil
?
show the reaction diagram
-
-
-
-
-
DNA with 5-hydroxy-2'-deoxyuridine/G
?
show the reaction diagram
-
-
-
-
-
DNA with 5-hydroxy-5-methylhydantoin
?
show the reaction diagram
-
-
-
-
-
DNA with 5-hydroxy-6-hydrothymine
?
show the reaction diagram
-
-
-
-
-
DNA with 5-hydroxy-6-hydrouracil
?
show the reaction diagram
-
-
-
-
-
DNA with alloxan
?
show the reaction diagram
-
-
-
-
-
DNA with an abasic site
?
show the reaction diagram
Q8ZVK6
-
-
-
?
DNA with an abasic site
?
show the reaction diagram
-
the enzyme is part of the base excision repair (BER) pathway. It protects from oxidative damage by removing the major product of DNA oxidation, 8-oxoguanine, from single- and double-stranded DNA substrates
-
-
?
DNA with an abasic site
?
show the reaction diagram
Q58134
the enzyme has little specificity for the base opposite 8-oxoguanine. The enzyme has both DNA glycosylase and DNA lyase (beta-elimination) activity, and the combined glycosylase/lyase activity occurs at a rate comparable with the glycosylase activity alone
-
-
?
DNA with an abasic site
?
show the reaction diagram
-
the substrate specificity for 8-oxoguanine/guanine sites is higher than that for 8-oxoguanine/cytosine sites. apurinic-lyase activity of this enzyme cleaved only 20% of these apurinic-sites at the same time point
-
-
?
DNA with an abasic site
?
show the reaction diagram
Pyrobaculum aerophilum DSM 7523
Q8ZVK6
-
-
-
?
DNA with an abasic site
?
show the reaction diagram
Pyrobaculum aerophilum DSM 7523
-
the enzyme is part of the base excision repair (BER) pathway. It protects from oxidative damage by removing the major product of DNA oxidation, 8-oxoguanine, from single- and double-stranded DNA substrates, the substrate specificity for 8-oxoguanine/guanine sites is higher than that for 8-oxoguanine/cytosine sites. apurinic-lyase activity of this enzyme cleaved only 20% of these apurinic-sites at the same time point
-
-
?
DNA with an abasic site
DNA with 5'-phosphate terminus + DNA with 3'-alpha,beta-unsaturated aldehyde
show the reaction diagram
O29876
the enzyme excises an oxidatively-damaged form of guanine. Bifunctional enzyme with both DNA glycosylase and apurinic/apyrimidinic lyase activities, bifunctional enzyme with both DNA glycosylase and apurinic/apyrimidinic lyase activities. The specificity of DNA glycosylase activity of is compared using 39-mer DNA duplexes containing an 8-oxoG residue opposite each of the four natural DNA bases (A, T, G and C). The enzyme efficiently cleaves oligomers containing 8-oxoG:C and 8-oxoG:G base pairs, less effective on oligomers containing 8-oxoG:T and 8-oxoG:A mispairs. The enzyme catalyzes a beta-elimination reaction at the apurinic site produced by excision of the 8-oxoguanine and thus generates a 5'-phosphate terminus and a 3'-alpha,beta-unsaturated aldehyde sugar terminus at the incision site. Bifunctional enzyme with both DNA glycosylase and apurinic/apyrimidinic lyase activities
-
-
?
DNA with dihydrouridine/G
?
show the reaction diagram
-
-
-
-
-
DNA with tetrahydrofuranyl/G
?
show the reaction diagram
-
-
-
-
-
DNA with thymine glycol
?
show the reaction diagram
-
-
-
-
-
DNA with uracil glycol
?
show the reaction diagram
-
-
-
-
-
double-stranded DNA with abasic sites
?
show the reaction diagram
-
-
-
-
?
duplex oligonucleotide containing a 5,6-dihydro-2'-deoxyuridine*G pair
?
show the reaction diagram
-
nucleotide incison repair activity
-
-
?
duplex oligonucleotide containing a alpha-2'-deoxyadenosine*T pair
?
show the reaction diagram
-
nucleotide incison repair activity
-
-
?
duplex oligonucleotide containing a tetrahydrofuran*G pair
?
show the reaction diagram
-
nucleotide incison repair activity
-
-
?
GTACGTAXCCACAGACAGTGATGA
?
show the reaction diagram
-
X: AP site
-
-
?
oligodeoxynucleotide with abasic site 2,3-dihydroxy-5-oxopentyl phosphate
?
show the reaction diagram
-
-
-
-
?
oligomer with G/U pair
?
show the reaction diagram
-
-
-
-
-
Red substrate 2
?
show the reaction diagram
-
-
-
-
?
single-stranded DNA with abasic sites
?
show the reaction diagram
-
catalytic efficiency is 20fold less than the activity against double-stranded DNA with abasic sites
-
-
?
THF-containing oligonucleotide
?
show the reaction diagram
-
AP endonuclease activity
-
-
?
linear 31-mer duplex oligonucleotide (3'-32P-labeled top strand contains an abasic site at position 17)
3'-32P-labeled 14-mer oligonucleotide
show the reaction diagram
-
cleavage 3' to the apurinic/apyrimidinic site
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
no associated exonuclease activity
-
-
-
additional information
?
-
-
gelonin, pokeweed antiviral protein and ricin belong to the family of ribosome-inactivating proteins with DNA-glycosylase/AP-lyase activities
-
-
-
additional information
?
-
-
unlike other endonucleases endonuclease IV or Exo III, Ape1 does not enhance the rate of product release with a G/A substrate
-
-
-
additional information
?
-
-
inositol polyphosphate 5-phosphatase enzymes show high homology to AP endonucleases in regions that correspond to catalytic residues, they also share a similar mechanism of catalysis to the AP endonuclease consistent with other common functional similarities such as an absolute requirement for magnesium
-
-
-
additional information
?
-
-
enzyme also has DNA N-glycosylase activity
-
-
-
additional information
?
-
-
enzyme also has DNA N-glycosylase activity
-
-
-
additional information
?
-
-
enzyme also has DNA N-glycosylase activity
-
-
-
additional information
?
-
P78549
enzyme also has DNA N-glycosylase activity
-
-
-
additional information
?
-
-
all known bacterial AP lyases and some at least of the mammalian ones, also acts as DNA glycosylases
-
-
-
additional information
?
-
-
no activity with DNA that has been damaged by UV light, methyl methanesulfonate, osmium teroxide or sodium bisulfite
-
-
-
additional information
?
-
-
enzyme has no biologically significant 3'-5'-exonuclease activity, the activity only manifests at enzyme concentrations elevated by 6-7 orders magnitude, activity does not show a preference to mismatched compared to matched DNA structures as well as to nicked or gapped DNA substrates
-
-
-
additional information
?
-
-
enzyme lacks 3'-endonuclease activity against undamaged DNA
-
-
-
additional information
?
-
-
bacteriophage T4 endonuclease V and Escherichia coli endonuclease II catalyze N-glycosylase and 3'-abasic endonuclease reaction, beta-elimination reaction
-
-
-
additional information
?
-
-
no substrate: alkylated sites
-
-
-
additional information
?
-
-
no substrate: alkylated sites
-
-
-
additional information
?
-
-
no substrate: alkylated sites
-
-
-
additional information
?
-
-
no substrate: alkylated sites
-
-
-
additional information
?
-
-
no substrate: alkylated sites
-
-
-
additional information
?
-
-
no substrate: native DNA
-
-
-
additional information
?
-
-
no substrate: native DNA
-
-
-
additional information
?
-
-
no substrate: native DNA
-
-
-
additional information
?
-
-
no substrate: native DNA
-
-
-
additional information
?
-
-
no substrate: native DNA
-
-
-
additional information
?
-
-
no substrate: native DNA
-
-
-
additional information
?
-
-
pdT8d(-)dTn is cleaved by endonuclease III yielding two products which have the same electrophoretic behaviour as the doublet obtained by alkaline beta-elimination, thus the enzyme is a beta-elimination catalyst
-
-
-
additional information
?
-
-
inactive on reduced AP sites
-
-
-
additional information
?
-
-
enzyme stimulates polymerase beta activity on the 5'-terminal oxidized abasic residue
-
-
-
additional information
?
-
-
corrects apurinic/apyrimidinic sites in the genome
-
-
-
additional information
?
-
-
multifunctional enzyme involved in DNA repair and redox regulation of transcription factors
-
-
-
additional information
?
-
Q9SIC4
major role in plant defence against oxidative DNA damage
-
-
-
additional information
?
-
-
important role in repair of oxidative DNA damage
-
-
-
additional information
?
-
-
key enzyme in repair of oxidatively damaged DNA
-
-
-
additional information
?
-
-
role in eliminating damaged mitochondrial genomes from the gene pool
-
-
-
additional information
?
-
P27695
catalyses the initial step in apruinic/apyrimidinic site repair
-
-
-
additional information
?
-
-
enzyme stimulates long patch base excision repair by cleaving the DNA and then facilitating the sequential binding and catalysis by DNA polymerase beta, DNA polymerase delta, FEN1 and DNA ligase I
-
-
-
additional information
?
-
-
AP endonuclease Ape1 is involved in the nucleotide incision repair pathway
-
-
-
additional information
?
-
-
APE1 exonuclease function appears to be modulated by the other BER proteins DNA polymerase beta and poly(ADP-ribose) polymerase 1. Excess APE1 over DNA polymerase beta may allow APE1 to perform both exonuclease function and stimulation of strand-displacement DNA synthesis by DNA polymerase beta
-
-
-
additional information
?
-
-
enzymatic repair of abasic sites, key intermediate step in base excision repair pathway
-
-
-
additional information
?
-
P23196
enzyme plays an important role in repair of DNA damages
-
-
-
additional information
?
-
-
overexpression of AP endonuclease protects Leishmania major cells against methotrexate induced DNA fragmentation and hydrogen peroxide, key enzyme in mediating repair of abasic sites in these pathogens
-
-
-
additional information
?
-
-
poly(ADP-ribose) polymerase-1 and apurinic/apyrimidinic endonuclease can interact with the same base excision repair intermediate. Competition between theses two proteins may influence their respective base excision repair related functions
-
-
-
additional information
?
-
-
the enzyme enhances methylpurine-DNA glycosylase-catalyzed excision, complex formation of methylpurine-DNA glycosylase eith proliferating cell nuclear antigen can accomodate binding of APE1
-
-
-
additional information
?
-
-
the enzyme has two distinct roles in the repair of oxidative DNA damage and in gene regulation. Absolute requirement of the enzyme for cell survival, presumably to protect against spontaneous oxidative DNA damage
-
-
-
additional information
?
-
-
the function of APE is considered as the rate-limiting step in DNA base excision repair. AP endonuclease suppresses DNA mismatch repair activity leading to microsatellite instability
-
-
-
additional information
?
-
O15527
hOgg1 protein catalyzes the excision of 8-oxo-7,8-dihydroguanine and the incision of apurinic and apyrimidinic sites in DNA
-
-
-
additional information
?
-
-
the enzyme remains bound to its incision product when the 5'-incision us in double-stranded DNA. The enzyme dissociates from its single-stranded 5'-incised product
-
-
-
additional information
?
-
-
a DNA base excision repair enzyme with a wide variety of functions, including AP endonuclease (cleaving an AP site 5' to a deoxyribose phosphate moiety), 3' exonuclease, 3' phosphodiesterase, 3' phosphatase, RNaseH, and 5' endonuclease activities
-
-
-
additional information
?
-
-
an increase of APE/Ref-1 mRNA levels in the caudal region of spinal cord strongly correlates with DNA damage after traumatic spinal cord injury
-
-
-
additional information
?
-
-
AP endo acts by a one-step associative phosphoryl transfer mechanism on a THF-containing substrate, AP endo acts on many types of DNA substrate molecules but demonstrates the most robust activity when acting as a class II AP endonuclease
-
-
-
additional information
?
-
-
APE/Ref-1 act as tuning molecule in activated B-cells, APE/Ref-1 affect the cell cycle by inducing nucleus-cytoplasm translocation of the cyclin-dependent kinase inhibitor p21
-
-
-
additional information
?
-
-
APE/Ref-1 is a critical component of the hypoxia-inducible transcriptional complex that interacts with hypoxia-inducible factor-1 and p300, APE/Ref-1 is a key regulator, it markedly induces and efficiently protects melanocytes from oxidative damage by inducing the antiapoptotic machinery and stimulating cell survival
-
-
-
additional information
?
-
-
APE1 appears to have endonucleolytic activity as a repair enzyme within the nucleotide incision repair pathway
-
-
-
additional information
?
-
-
APE1 binds with the highest efficiency to DNA substrate containing 5'-sugar phosphate group in the nick/gap
-
-
-
additional information
?
-
-
APE1 can incise DNA at the 5'-position of oxidized pyrimidine bases such as 5,6-dihydro-thymine or 5,6-dihydro-2'-deoxyuracil (DHU), thus initiating a repair process known as nucleotide incision repair (NIR)
-
-
-
additional information
?
-
-
APE1 exhibits 3'-phosphodiesterase, 3'-phosphatase, and 3'-5'-exonuclease activities
-
-
-
additional information
?
-
P27695
APE1 has been identified as a protein capable of nuclear redox activity, inducing the DNA binding activity of several transcription factors, such as activator protein-1, nuclear factor-kappaB, Myb, polyoma virus enhancer-binding protein-2, HLF, nuclear factor-Y, early growth response protein-1, hypoxia inducible factor-1alpha, ATF/CREB family, p53, and Pax proteins. In each case, this effect is accomplished by maintaining the cysteine residues of the transcription factors in the reduced state.
-
-
-
additional information
?
-
-
APE1 has DNA 3'-phosphatase activity in vitro and 3' to 5' exonuclease activity, which could be physiologically relevant in the removal of mismatched or damaged nucleotides incorporated during the synthesis step of BER
-
-
-
additional information
?
-
-
Ape1 has the ability to incise at AP sites in DNA conformations formed during DNA replication, transcription, and class switch recombination, and that Ape1 can endonucleolytically destroy damaged RNA
-
-
-
additional information
?
-
-
APE1 hydrolytically cleaves the phosphodiester backbone 5' to the AP site, leaving a 3'-hydroxyl and a 5'-abasic deoxyribose phosphate to be processed by the subsequent cascade of BER enzymes, APE1 is a fundamental protein in this essential repair pathway and is thought to be responsible for more than 95% of total AP endonuclease activity in human cell culture extracts
-
-
-
additional information
?
-
-
Ape1 is a multifunctional enzyme of 318 amino acids with redox-dependent regulation of transcription factors, 3' to 5' exonuclease, 3' phosphodiesterase, RNaseH and class II type AP endonuclease activities
-
-
-
additional information
?
-
-
APE1 is also named as redox effector factor-1 because of its redox abilities on different redox-regulated transcription factors
-
-
-
additional information
?
-
P27695
APE1 is directly responsible for the control of the intracellular ROS levels through its inhibitory effect on Rac1, the regulatory subunit of a membrane nonphagocytic NADPH oxidase system.
-
-
-
additional information
?
-
-
APE1 is one of the candidates for the role of base excision repair (BER) pathway coordinator, which controls the whole process. APE1 participates in stimulation of activity of BER enzymes
-
-
-
additional information
?
-
-
APE1 recognizes AP sites in DNA that arise either spontaneously or as enzymatic products of DNA repair glycosylases that excise substrate base lesions as part of the base excision repair (BER) response. Subsequent to damage recognition, the chemistry central to the function of APE1 is wateractivated by a Mg2+ ion followed by hydrolytic cleavage of the phosphodiester bond immediately 5' to the abasic site
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additional information
?
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APE1 stimulates DNA synthesis catalyzed by DNA polymerase beta, and a human Xray repair cross-complementing group 1 protein stimulates APE1 3'-5'-exonuclease activity on 3'-recessed DNA duplex
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additional information
?
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APE1 utilizes a site located in its N-terminus for redox regulation of important transcription factors such as NF-kappaB, p53, c-Fos, and c-Jun
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-
additional information
?
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APE1/Ref-1 also has a complex relationship to high-mobility group box 1, a protein secreted by immune cells in response to inflammatory stimuli. APE1/Ref-1 can both promote and suppress inflammatory signaling induced by high-mobility group box 1, APE1/Ref-1 plays a complex role in the activation of nuclear factor kappa B, a key transcription factor involved in inflammatory and immune signaling, APE1/Ref-1 plays a role in cardiovascular physiology and pathophysiology. APE1/Ref-1 suppresses myocardial ischemia-reperfusion injury and vascular inflammation, and promotes endothelium-dependent vascular relaxation
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additional information
?
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APE1/Ref-1 promotes the effect of angiotensin II on Ca2+-activated K+-channel in human endothelial cells via suppression of NADPH oxidase, APE1/Ref-1 reduces oxidative stress by regulating the level of reactive oxygen species in the cytoplasm
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-
additional information
?
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APEs have 2 intrinsic activities in DNA repair. They act as an endonuclease in cleaving AP sites to generate 3' OH and 5' phosphodeoxyribose termini. They also act as a 3' phosphodiesterase/exonuclease to remove 3' blocking phosphodeoxyribose or its fragments generated during strand breaks, and by reactive oxygen species or DNA glycosylases that excise oxidized bases in the first step of base excision repair
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additional information
?
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APEX1 is a protein involved both in the base excision repair pathways of DNA lesions and in the regulation of gene expression as a redox coactivator of different transcription factors, such as early growth response protein-1, apurinic/apyrimidinic endonuclease 1 participates in the base excision repair of premutagenic apurinic/apyrimidinic (AP) sites
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-
additional information
?
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-
catalytic subunit of the HSV-1 DNA polymerase (Pol) (UL30) exhibits apurinic/apyrimidinic (AP) and 5'-deoxyribose phosphate lyase activities which are integral to base excision repair and lead to DNA cleavage on the 3'-side of abasic sites and 5'-deoxyribose-5-phosphate residues that remain after cleavage by 5'-AP endonuclease. DNA lyase activity residues in the Pol domain of UL30.
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additional information
?
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DNA with the recessed 3'-end (DNArec) is one of the preferential substrates for APE1 3'-5'-exonuclease activity
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additional information
?
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enzyme cleaves the AP sites in DNA and allows them to be repaired by other enzymes involved in base excision repair
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additional information
?
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enzyme cleaves the DNA sugar phosphate backbone at the 5'-position in relation to the AP site, forming a nick with the hydroxyl group at the 3'-end and deoxyribose phosphate at the 5'-end
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additional information
?
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enzyme has an essential base excision repair (BER) activity and a redox activity that regulates expression of a number of genes through reduction of their transcription factors, AP-1, NFkappaB, HIF-1alpha, CREB, p53 and others
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additional information
?
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enzyme has implications on the role of BER in viral genome maintenance during lytic replication and reactivation from latency
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additional information
?
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enzyme has the ability to reductively activate redoxsensitive transcription factors and negative gene regulation by extracellular calcium
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additional information
?
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enzyme plays a role in controlling CD40-mediated B-cell proliferation, increase in proliferation and decrease in apoptosis of primary mouse B-cells activated by CD40 cross-linking and transfected with functional APE/Ref-1 antisense oligonucleotide.
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additional information
?
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enzyme stimulates the DNA binding activity of the AP-1 family of transcription factors via a redox-dependent mechanism
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additional information
?
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forced cytoplasmic overexpression of APE1 profoundly attenuates the upregulation of high-mobility group box 1-mediated reactive oxygen species generation, cytokine secretion, and cyclooxygenase-2 expression by primary monocytes and macrophage-like THP-1 cell lines
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additional information
?
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high APE1 affinity to dsDNA
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additional information
?
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high-mobility group box 1-induced activation of p38 and c-Jun N-terminal kinase is strongly abrogated by the overexpression of APE1
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additional information
?
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hNTH1 and Y-box-binding protein-1 may be part of the same DNA repair pathway in response to cisplatin and UV treatments, hNTH1 binds directly to Y-box-binding protein-1 in the absence of nucleic acids, it binds to the auto-inhibitory n-terminal tail of NTH1
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additional information
?
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human Ape1 is a multifunctional protein with a major role in initiating repair of apurinic/apyrimidinic (AP) sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage
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additional information
?
-
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human apurinic/apyrimidinic endonuclease 1 is a major constituent of the base excision repair (BER) pathway of AP sites of DNA lesions. APE1 specifically binds to abasic sites and cuts the 5'-phosphodiester bond with its endonuclease activity to produce a DNA primer with 3'-hydroxyl end, which is a required step in the BER repair pathway
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additional information
?
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human endonuclease III is a relevant target to potentiate cisplatin cytotoxicity in Y-box-binding protein-1 overexpressing tumor cells
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additional information
?
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In addition to its primary AP site incision function, APE1 exhibits 3'-5' exonuclease, 3'-phosphodiesterase and RNase H catalysis, and a 3'-phosphatase activity
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-
additional information
?
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In addition to the exonuclease function, human APE1 is endowed with another enzymatic activity potentially relevant for the protection against oxidative damage, In human cells, APE1 excises sugar fragments that block the 3'-ends thus facilitating DNA repair synthesis
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additional information
?
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increase in phosphorylation of p53 after a decrease in Ape1 levels in sensory neuronal cultures
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additional information
?
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LMAP shares with APE1 the overall 3D structure and most of the catalytic groups in their active sites and can catalyze the removal of damaged nucleotides and phosphate groups from 3'-ends more efficiently than APE1
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additional information
?
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major factor in the maintenance of the integrity of the human genome
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additional information
?
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multifunctional protein involved in base excision DNA repair and in transcriptional regulation of gene expression, importance to genomic stability and cell survival
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additional information
?
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multifunctional protein involved in both the repair of oxidative and alkylating DNA damage and the regulation of gene expression
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-
additional information
?
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multifunctional protein involved in reduction-oxidation regulation. It functions as a redox factor that maintains transcription factors in an active reduced state
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additional information
?
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P27695
multifunctional protein possessing both DNA repair and transcriptional regulatory activities, has a pleiotropic role in controlling cellular response to oxidative stress. APE1 is the main apurinic/apyrimidinic endonuclease in eukaryotic cells, playing a central role in the DNA base excision repair pathway of all DNA lesions (uracil, alkylated and oxidized, and abasic sites), including single-strand breaks, and has also co-transcriptional activity by modulating genes expression directly regulated by either ubiquitous and tissue specific transcription factors. It controls the intracellular redox state by inhibiting the reactive oxygen species production
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additional information
?
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ntg1 possesses N-glycosylase/AP lyase activity that allows recognition and repair of oxidative base damage (primarily of pyrimidines) as well as abasic sites, ntg2 possesses N-glycosylase/AP lyase activity that allows recognition and repair of oxidative base damage (primarily of pyrimidines) as well as abasic sites
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additional information
?
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overexpressing wild-type Ape1 attentuates all the toxic effects of cisplatin in cells containing normal endogenous levels of Ape1 and in cells with reduced Ape1 levels after Ape1siRNA treatment
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additional information
?
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overexpression of APE1/Ref-1 suppressed angiotensin II induced production of superoxide and hydrogen peroxide
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additional information
?
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reducing expression of Ape1 in neuronal cultures using small interfering RNA enhances cisplatin-induced cell killing, apoptosis, ROS generation and cisplatin-induced reduction in iCGRP release
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additional information
?
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regulation of APEX1 expression by S-adenosylmethionine, which may be one of the mechanisms of hepatocellular carconom formation
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additional information
?
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small interfering RNA knockdown of endogenous APE1 impairs high-mobility group box 1-mediated cytokine expression and MAPK activation in THP-1 cells. High-mobility group box 1-stimulation induces the translocation of APE1 to the nucleus of the cell
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additional information
?
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The BK-Ca current in APE1/Ref-1-overexpressing human umbilical vein endothelial cells is similarly inhibited by angiotensin II, except that inhibition of 43.06% is achieved using only 10 nM angiotensin II
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additional information
?
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the DNA-binding ability of NF-kappaB in the Ape1/Ref-1 expressing cells is significantly increased
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additional information
?
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the key function is to produce a 3' OH terminus that serves as a primer for repair synthesis.
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additional information
?
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ubiquitously expressed protein that functions as both an endonuclease in the repair of oxidatively damaged DNA and an aid in the binding of redox-sensitive transcription factors
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additional information
?
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When APE1 and DNA polymerase beta are both present, a ternary complex APE1-DNA polymerase beta-DNA is formed with the highest efficiency with DNA product of APE1 endonuclease activity and with DNA containing 5'-flap or mononucleotide-gapped DNA with 5'-p group
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additional information
?
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25-mer oligonucleotide 5'-labeled with P32 containing tetrahydrofuran as abasic site analog
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additional information
?
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AP endo cleaves the Rp but not the Sp stereoisomer of DNA phosphorothioate oligomers, albeit slowly with respect to a phosphodiester substrate
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additional information
?
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APE1 most efficiently binds to DNA substrate bearing tetrahydrofuran in the middle of one of the strands (AP-dsDNA), for APE1 in MEF extract, efficiency of formation of protein-DNA crosslinking changes depending on the nature of 5'-group flanking the nick in DNA structure: DNAFAP-pF (100%), DNAFAP-OH (68.2%), DNAFAP-flap (54.6%), DNAFAP-gap (44.2%), DNAFAP-rec (41.3%), DNAFAP-p (41.1%)
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additional information
?
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The ratio of AP endo reaction product to STM7 49mer hairpin oligomers is varied. Product formation is maximal with an 8:1 ratio of STM7 acceptor to 5' thiophosphate donor DNA and by addition of extra ATP (0.5 mM) and ligase (60 units) midreaction
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additional information
?
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Used oligonucleotides are 54mers annealed to a complementary 18mer DNA to form the partial duplex substrates (54F-endbubble or 54F-centerbubble with 18DNA) and two 54mers annealed to create an 18-nt bubble structure (54Fendbubble or 54Fcenterbubble with 54bubble18comp). The abasic site is either centrally located (center bubble DNAs) or located at the ssDNA-dsDNA junction (end bubble DNAs). Ape1 most efficiently incised at an abasic site located centrally in the 18-nt bubble structure (54Fcenterbubble18-54bubblecomp), followed by the centrally located abasic site in the partial duplex DNA (54Fcenterbubble18-18DNA), the abasic site at an ssDNA/dsDNA junction in the bubble conformation (54Fendbubble18-54bubblecomp), and the abasic site at an ssDNA/dsDNA junction in partial duplex DNA (54Fendbubble18-18DNA)
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additional information
?
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APE1 at low concentrations does not have any effect on 5'-Cy3-CrUAGGTAGTTATCCrUAG-Black Hole Quencher1-3' (OligoII), under similar conditions, the recombinant APE1 has no effect on fluorescently labeled or 32P-labeled DNAOligoI
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additional information
?
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KsgA does not remove C opposite normal bases, 7,8-dihydro-8-oxoguanine and 2-hydroxyadenine, KsgA does not excise thymine glycol, 5-formyluracil, and 5-hydroxymethyluracil opposite cytosine from double-stranded oligonucleotides
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additional information
?
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a 2'-OH on the sugar moiety is absolutely required for RNA cleavage by wild-type APE1, consistent with APE1 leaving a 3'-PO4 2? group following cleavage of RNA. the catalytic mechanisms for cleaving RNA, abasic single-stranded RNA, and abasic DNA are not identical
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additional information
?
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APE1 adopts a partially unfolded state, which is proposed to be the redox active form of the enzyme
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additional information
?
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DNA polymerase beta approaches the Ape1-DNA complex downstream of the incision site, displaces Ape1-DNA binding contacts including residues K227, K228, and K276, and in the process makes minimal interactions with lysine residues in the Ref1 domain, i.e. N-terminal residues 43-93
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additional information
?
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DNA polymerase X, along with polymerization and 3'-5'-exonuclease activities, possesses an intrinsic abasic endonuclease activity. Both, abasic endonuclease and 3'-5'-exonuclease activities are genetically linked and governed by the same metal ligands located at the C-terminal polymerase and histidinol phosphatase domain of the polymerase
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additional information
?
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wild-type APE1 undergoes at least four conformational transitions during the processing of abasic sites in DNA. Nonspecific interactions of APE1 with undamaged DNA can be described by a two-step kinetic scheme. APE1 molecule undergoes at least four conformational transitions, including nonspecific encounter complex formation, mutual adjustment of the enzyme and DNA substrate structures for catalysis, catalytic incision of the substrate, and release of the enzyme from its complex with the product. The C1'-hydroxyl moiety of the abasic site is required for the most effective recognition and catalysis
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additional information
?
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enzyme displays AP endonuclease, 3'-repair phosphodiesterase, 3'-phosphatase and 3'-5' exonuclease activities. Enzyme removes 3'-blocking sugar-phosphate and 3'-phosphate groups with good efficiency but possesses a very weak AP endonuclease activity as compared to the human homologue APE1
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additional information
?
-
Escherichia coli KSR7
-
KsgA does not remove C opposite normal bases, 7,8-dihydro-8-oxoguanine and 2-hydroxyadenine, KsgA does not excise thymine glycol, 5-formyluracil, and 5-hydroxymethyluracil opposite cytosine from double-stranded oligonucleotides
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
AP DNA
fragments of DNA
show the reaction diagram
-
AP sites
-
-
?
AP-DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
AP-DNA
fragments of DNA
show the reaction diagram
P27695
Base excision repair pathway, enzyme cleaves the 5'-phosphodiester bond, generating 3'-OH and 5'-dRP termini
-
-
?
AP-DNA
fragments of DNA
show the reaction diagram
Escherichia coli BW565DE3
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
P27695
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
O15527
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
P78549
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
Q9SIC4
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
O35980
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
base excision repair (BERa) pathway is initiated by lesion-specific glycosylases that excise the damaged base from the sugar-phosphate backbone, resulting in a potentially cytotoxic apurinic/apyrimidinic (AP) site intermediate that becomes the substrate for the major human AP endonuclease
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
bifunctional enzyme is involved in base excision repair, it is a bifunctional DNA glycosylase/apurinic/apyrimidinic lyase which removes hydrated, reduced, or oxidized bases from the DNA backbone as the initial step of base excision repair
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
DNA repair enzyme is involved in base excision repair of apurinic/apyrimidinic sites after oxidative DNA damage
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
DNA single-strand breaks containing 3'-blocking groups are generated from attack of the sugar backbone by reactive oxygen species or after base excision by DNA glycosylase, apurinic, apyrimidinic (AP) lyases
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
DNA single-strand breaks containing 3'-blocking groups are generated from attack of the sugar backbone by reactive oxygen species or after base excision by DNA glycosylase/apurinic/apyrimidinic (AP) lyases
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
enzyme plays an important role in oxidative signalling, transcription factor regulation, and cell cycle control
-
-
ir
DNA
fragments of DNA
show the reaction diagram
-
multifunctional enzyme involved in DNA base excision repair of oxidative DNA damage and in redox regulation of a number of transcription factors
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
oxidative DNA damage is primarily reversed by the base excision repair pathway, initiated by N-glycosylase apurinic/apyrimidinic lyase proteins
-
-
ir
DNA
fragments of DNA
show the reaction diagram
-
The latter lesions are processed by AP endonucleases, which are important components of the base excision repair pathway
-
-
?
DNA
fragments of DNA
show the reaction diagram
Bacillus subtilis PS832
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
Saccharomyces cerevisiae D273-10B/A1
-
-
-
-
?
DNA
fragments of DNA
show the reaction diagram
-
-
-
-
?
DNA containing apurinic/apyrimidinic site
DNA fragments
show the reaction diagram
-
-
-
-
?
DNA containing apurinic/apyrimidinic sites
fragments of DNA
show the reaction diagram
-
apurinic/apyrimidinic endonuclease Nfo protects Bacillus subtilis spores from DNA damage accumulated during spore dormancy
-
-
?
DNA containing apurinic/apyrimidinic sites
fragments of DNA
show the reaction diagram
-
C4'-oxidized abasic sites are efficiently excised via intermediate Schiff-base formation. Activity is 100fold less efficient than repair by exonuclease III
-
-
?
DNA containing apurinic/apyrimidinic sites
fragments of DNA
show the reaction diagram
-
hydrogen bonds to phosphate groups 3' to the cleavage site is essential for the binding of the enzyme to the product DNA, which may be necessary for efficient functioning of the base excision rapair pathway
-
-
?
DNA containing apurinic/apyrimidinic sites
fragments of DNA
show the reaction diagram
Q9AIV4
inducible enzyme, the enzyme exhibits endonucleolytic activity and is regulated as part of the acid-adaptive response of the organism. Smx is likely the primary, if not the sole, AP endonuclease induced during growth at low pH values, loss of Smx activity renders the mutant strain sensitive to hydrogen peroxide treatment but relatively unaffected by acid-mediated damage or near-UV irradiation
-
-
?
DNA containing tamdem dihydrouracil
?
show the reaction diagram
-
the human AP endonuclease APE1 can process the 3' termini generated by human endonuclease III (hNTH) and endonuclease VIII. Both human endonuclease III and endonuclease VIII cannot completely remove both dihydrouracil lesions. With the participation of APE1 and polynucleotide kinase, the 3'-lesions remaining in the products of the reaction with human endonuclease III and endonuclease VIII can efficiently removed. The resulting products can be utilized by repair DNA polymerases as primers for repair synthesis
-
-
?
DNA containing tandem dihydrouracil
?
show the reaction diagram
-
the human AP endonuclease APE1 can process the 3' termini generated by human endonuclease III (hNTH) and endonuclease VIII. Both human endonuclease III and endonuclease VIII cannot completely remove both dihydrouracil lesions. With the participation of APE1 and polynucleotide kinase, the 3'-lesions remaining in the products of the reaction with human endonuclease III and endonuclease VIII can efficiently removed. The resulting products can be utilized by repair DNA polymerases as primers for repair synthesis
-
-
?
DNA with an abasic site
?
show the reaction diagram
-
the enzyme is part of the base excision repair (BER) pathway. It protects from oxidative damage by removing the major product of DNA oxidation, 8-oxoguanine, from single- and double-stranded DNA substrates
-
-
?
DNA with an abasic site
DNA with 5'-phosphate terminus + DNA with 3'-alpha,beta-unsaturated aldehyde
show the reaction diagram
O29876
the enzyme excises an oxidatively-damaged form of guanine. Bifunctional enzyme with both DNA glycosylase and apurinic/apyrimidinic lyase activities
-
-
?
DNA with an abasic site
?
show the reaction diagram
Pyrobaculum aerophilum DSM 7523
-
the enzyme is part of the base excision repair (BER) pathway. It protects from oxidative damage by removing the major product of DNA oxidation, 8-oxoguanine, from single- and double-stranded DNA substrates
-
-
?
additional information
?
-
-
enzyme stimulates polymerase beta activity on the 5'-terminal oxidized abasic residue
-
-
-
additional information
?
-
-
corrects apurinic/apyrimidinic sites in the genome
-
-
-
additional information
?
-
-
multifunctional enzyme involved in DNA repair and redox regulation of transcription factors
-
-
-
additional information
?
-
Q9SIC4
major role in plant defence against oxidative DNA damage
-
-
-
additional information
?
-
-
important role in repair of oxidative DNA damage
-
-
-
additional information
?
-
-
key enzyme in repair of oxidatively damaged DNA
-
-
-
additional information
?
-
-
role in eliminating damaged mitochondrial genomes from the gene pool
-
-
-
additional information
?
-
P27695
catalyses the initial step in apruinic/apyrimidinic site repair
-
-
-
additional information
?
-
-
enzyme stimulates long patch base excision repair by cleaving the DNA and then facilitating the sequential binding and catalysis by DNA polymerase beta, DNA polymerase delta, FEN1 and DNA ligase I
-
-
-
additional information
?
-
-
AP endonuclease Ape1 is involved in the nucleotide incision repair pathway
-
-
-
additional information
?
-
-
APE1 exonuclease function appears to be modulated by the other BER proteins DNA polymerase beta and poly(ADP-ribose) polymerase 1. Excess APE1 over DNA polymerase beta may allow APE1 to perform both exonuclease function and stimulation of strand-displacement DNA synthesis by DNA polymerase beta
-
-
-
additional information
?
-
-
enzymatic repair of abasic sites, key intermediate step in base excision repair pathway
-
-
-
additional information
?
-
P23196
enzyme plays an important role in repair of DNA damages
-
-
-
additional information
?
-
-
overexpression of AP endonuclease protects Leishmania major cells against methotrexate induced DNA fragmentation and hydrogen peroxide, key enzyme in mediating repair of abasic sites in these pathogens
-
-
-
additional information
?
-
-
poly(ADP-ribose) polymerase-1 and apurinic/apyrimidinic endonuclease can interact with the same base excision repair intermediate. Competition between theses two proteins may influence their respective base excision repair related functions
-
-
-
additional information
?
-
-
the enzyme enhances methylpurine-DNA glycosylase-catalyzed excision, complex formation of methylpurine-DNA glycosylase eith proliferating cell nuclear antigen can accomodate binding of APE1
-
-
-
additional information
?
-
-
the enzyme has two distinct roles in the repair of oxidative DNA damage and in gene regulation. Absolute requirement of the enzyme for cell survival, presumably to protect against spontaneous oxidative DNA damage
-
-
-
additional information
?
-
-
the function of APE is considered as the rate-limiting step in DNA base excision repair. AP endonuclease suppresses DNA mismatch repair activity leading to microsatellite instability
-
-
-
additional information
?
-
-
a DNA base excision repair enzyme with a wide variety of functions, including AP endonuclease (cleaving an AP site 5' to a deoxyribose phosphate moiety), 3' exonuclease, 3' phosphodiesterase, 3' phosphatase, RNaseH, and 5' endonuclease activities
-
-
-
additional information
?
-
-
an increase of APE/Ref-1 mRNA levels in the caudal region of spinal cord strongly correlates with DNA damage after traumatic spinal cord injury
-
-
-
additional information
?
-
-
AP endo acts by a one-step associative phosphoryl transfer mechanism on a THF-containing substrate, AP endo acts on many types of DNA substrate molecules but demonstrates the most robust activity when acting as a class II AP endonuclease
-
-
-
additional information
?
-
-
APE/Ref-1 act as tuning molecule in activated B-cells, APE/Ref-1 affect the cell cycle by inducing nucleus-cytoplasm translocation of the cyclin-dependent kinase inhibitor p21
-
-
-
additional information
?
-
-
APE/Ref-1 is a critical component of the hypoxia-inducible transcriptional complex that interacts with hypoxia-inducible factor-1 and p300, APE/Ref-1 is a key regulator, it markedly induces and efficiently protects melanocytes from oxidative damage by inducing the antiapoptotic machinery and stimulating cell survival
-
-
-
additional information
?
-
-
APE1 appears to have endonucleolytic activity as a repair enzyme within the nucleotide incision repair pathway
-
-
-
additional information
?
-
-
APE1 binds with the highest efficiency to DNA substrate containing 5'-sugar phosphate group in the nick/gap
-
-
-
additional information
?
-
-
APE1 can incise DNA at the 5'-position of oxidized pyrimidine bases such as 5,6-dihydro-thymine or 5,6-dihydro-2'-deoxyuracil (DHU), thus initiating a repair process known as nucleotide incision repair (NIR)
-
-
-
additional information
?
-
-
APE1 exhibits 3'-phosphodiesterase, 3'-phosphatase, and 3'-5'-exonuclease activities
-
-
-
additional information
?
-
P27695
APE1 has been identified as a protein capable of nuclear redox activity, inducing the DNA binding activity of several transcription factors, such as activator protein-1, nuclear factor-kappaB, Myb, polyoma virus enhancer-binding protein-2, HLF, nuclear factor-Y, early growth response protein-1, hypoxia inducible factor-1alpha, ATF/CREB family, p53, and Pax proteins. In each case, this effect is accomplished by maintaining the cysteine residues of the transcription factors in the reduced state.
-
-
-
additional information
?
-
-
APE1 has DNA 3'-phosphatase activity in vitro and 3' to 5' exonuclease activity, which could be physiologically relevant in the removal of mismatched or damaged nucleotides incorporated during the synthesis step of BER
-
-
-
additional information
?
-
-
Ape1 has the ability to incise at AP sites in DNA conformations formed during DNA replication, transcription, and class switch recombination, and that Ape1 can endonucleolytically destroy damaged RNA
-
-
-
additional information
?
-
-
APE1 hydrolytically cleaves the phosphodiester backbone 5' to the AP site, leaving a 3'-hydroxyl and a 5'-abasic deoxyribose phosphate to be processed by the subsequent cascade of BER enzymes, APE1 is a fundamental protein in this essential repair pathway and is thought to be responsible for more than 95% of total AP endonuclease activity in human cell culture extracts
-
-
-
additional information
?
-
-
Ape1 is a multifunctional enzyme of 318 amino acids with redox-dependent regulation of transcription factors, 3' to 5' exonuclease, 3' phosphodiesterase, RNaseH and class II type AP endonuclease activities
-
-
-
additional information
?
-
-
APE1 is also named as redox effector factor-1 because of its redox abilities on different redox-regulated transcription factors
-
-
-
additional information
?
-
P27695
APE1 is directly responsible for the control of the intracellular ROS levels through its inhibitory effect on Rac1, the regulatory subunit of a membrane nonphagocytic NADPH oxidase system.
-
-
-
additional information
?
-
-
APE1 is one of the candidates for the role of base excision repair (BER) pathway coordinator, which controls the whole process. APE1 participates in stimulation of activity of BER enzymes
-
-
-
additional information
?
-
-
APE1 recognizes AP sites in DNA that arise either spontaneously or as enzymatic products of DNA repair glycosylases that excise substrate base lesions as part of the base excision repair (BER) response. Subsequent to damage recognition, the chemistry central to the function of APE1 is wateractivated by a Mg2+ ion followed by hydrolytic cleavage of the phosphodiester bond immediately 5' to the abasic site
-
-
-
additional information
?
-
-
APE1 stimulates DNA synthesis catalyzed by DNA polymerase beta, and a human Xray repair cross-complementing group 1 protein stimulates APE1 3'-5'-exonuclease activity on 3'-recessed DNA duplex
-
-
-
additional information
?
-
-
APE1 utilizes a site located in its N-terminus for redox regulation of important transcription factors such as NF-kappaB, p53, c-Fos, and c-Jun
-
-
-
additional information
?
-
-
APE1/Ref-1 also has a complex relationship to high-mobility group box 1, a protein secreted by immune cells in response to inflammatory stimuli. APE1/Ref-1 can both promote and suppress inflammatory signaling induced by high-mobility group box 1, APE1/Ref-1 plays a complex role in the activation of nuclear factor kappa B, a key transcription factor involved in inflammatory and immune signaling, APE1/Ref-1 plays a role in cardiovascular physiology and pathophysiology. APE1/Ref-1 suppresses myocardial ischemia-reperfusion injury and vascular inflammation, and promotes endothelium-dependent vascular relaxation
-
-
-
additional information
?
-
-
APE1/Ref-1 promotes the effect of angiotensin II on Ca2+-activated K+-channel in human endothelial cells via suppression of NADPH oxidase, APE1/Ref-1 reduces oxidative stress by regulating the level of reactive oxygen species in the cytoplasm
-
-
-
additional information
?
-
-
APEs have 2 intrinsic activities in DNA repair. They act as an endonuclease in cleaving AP sites to generate 3' OH and 5' phosphodeoxyribose termini. They also act as a 3' phosphodiesterase/exonuclease to remove 3' blocking phosphodeoxyribose or its fragments generated during strand breaks, and by reactive oxygen species or DNA glycosylases that excise oxidized bases in the first step of base excision repair
-
-
-
additional information
?
-
-
APEX1 is a protein involved both in the base excision repair pathways of DNA lesions and in the regulation of gene expression as a redox coactivator of different transcription factors, such as early growth response protein-1, apurinic/apyrimidinic endonuclease 1 participates in the base excision repair of premutagenic apurinic/apyrimidinic (AP) sites
-
-
-
additional information
?
-
-
catalytic subunit of the HSV-1 DNA polymerase (Pol) (UL30) exhibits apurinic/apyrimidinic (AP) and 5'-deoxyribose phosphate lyase activities which are integral to base excision repair and lead to DNA cleavage on the 3'-side of abasic sites and 5'-deoxyribose-5-phosphate residues that remain after cleavage by 5'-AP endonuclease. DNA lyase activity residues in the Pol domain of UL30.
-
-
-
additional information
?
-
-
DNA with the recessed 3'-end (DNArec) is one of the preferential substrates for APE1 3'-5'-exonuclease activity
-
-
-
additional information
?
-
-
enzyme cleaves the AP sites in DNA and allows them to be repaired by other enzymes involved in base excision repair
-
-
-
additional information
?
-
-
enzyme cleaves the DNA sugar phosphate backbone at the 5'-position in relation to the AP site, forming a nick with the hydroxyl group at the 3'-end and deoxyribose phosphate at the 5'-end
-
-
-
additional information
?
-
-
enzyme has an essential base excision repair (BER) activity and a redox activity that regulates expression of a number of genes through reduction of their transcription factors, AP-1, NFkappaB, HIF-1alpha, CREB, p53 and others
-
-
-
additional information
?
-
-
enzyme has implications on the role of BER in viral genome maintenance during lytic replication and reactivation from latency
-
-
-
additional information
?
-
-
enzyme has the ability to reductively activate redoxsensitive transcription factors and negative gene regulation by extracellular calcium
-
-
-
additional information
?
-
-
enzyme plays a role in controlling CD40-mediated B-cell proliferation, increase in proliferation and decrease in apoptosis of primary mouse B-cells activated by CD40 cross-linking and transfected with functional APE/Ref-1 antisense oligonucleotide.
-
-
-
additional information
?
-
-
enzyme stimulates the DNA binding activity of the AP-1 family of transcription factors via a redox-dependent mechanism
-
-
-
additional information
?
-
-
forced cytoplasmic overexpression of APE1 profoundly attenuates the upregulation of high-mobility group box 1-mediated reactive oxygen species generation, cytokine secretion, and cyclooxygenase-2 expression by primary monocytes and macrophage-like THP-1 cell lines
-
-
-
additional information
?
-
-
high APE1 affinity to dsDNA
-
-
-
additional information
?
-
-
high-mobility group box 1-induced activation of p38 and c-Jun N-terminal kinase is strongly abrogated by the overexpression of APE1
-
-
-
additional information
?
-
-
hNTH1 and Y-box-binding protein-1 may be part of the same DNA repair pathway in response to cisplatin and UV treatments, hNTH1 binds directly to Y-box-binding protein-1 in the absence of nucleic acids, it binds to the auto-inhibitory n-terminal tail of NTH1
-
-
-
additional information
?
-
-
human Ape1 is a multifunctional protein with a major role in initiating repair of apurinic/apyrimidinic (AP) sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage
-
-
-
additional information
?
-
-
human apurinic/apyrimidinic endonuclease 1 is a major constituent of the base excision repair (BER) pathway of AP sites of DNA lesions. APE1 specifically binds to abasic sites and cuts the 5'-phosphodiester bond with its endonuclease activity to produce a DNA primer with 3'-hydroxyl end, which is a required step in the BER repair pathway
-
-
-
additional information
?
-
-
human endonuclease III is a relevant target to potentiate cisplatin cytotoxicity in Y-box-binding protein-1 overexpressing tumor cells
-
-
-
additional information
?
-
-
In addition to its primary AP site incision function, APE1 exhibits 3'-5' exonuclease, 3'-phosphodiesterase and RNase H catalysis, and a 3'-phosphatase activity
-
-
-
additional information
?
-
-
In addition to the exonuclease function, human APE1 is endowed with another enzymatic activity potentially relevant for the protection against oxidative damage, In human cells, APE1 excises sugar fragments that block the 3'-ends thus facilitating DNA repair synthesis
-
-
-
additional information
?
-
-
increase in phosphorylation of p53 after a decrease in Ape1 levels in sensory neuronal cultures
-
-
-
additional information
?
-
-
LMAP shares with APE1 the overall 3D structure and most of the catalytic groups in their active sites and can catalyze the removal of damaged nucleotides and phosphate groups from 3'-ends more efficiently than APE1
-
-
-
additional information
?
-
-
major factor in the maintenance of the integrity of the human genome
-
-
-
additional information
?
-
-
multifunctional protein involved in base excision DNA repair and in transcriptional regulation of gene expression, importance to genomic stability and cell survival
-
-
-
additional information
?
-
-
multifunctional protein involved in both the repair of oxidative and alkylating DNA damage and the regulation of gene expression
-
-
-
additional information
?
-
-
multifunctional protein involved in reduction-oxidation regulation. It functions as a redox factor that maintains transcription factors in an active reduced state
-
-
-
additional information
?
-
P27695
multifunctional protein possessing both DNA repair and transcriptional regulatory activities, has a pleiotropic role in controlling cellular response to oxidative stress. APE1 is the main apurinic/apyrimidinic endonuclease in eukaryotic cells, playing a central role in the DNA base excision repair pathway of all DNA lesions (uracil, alkylated and oxidized, and abasic sites), including single-strand breaks, and has also co-transcriptional activity by modulating genes expression directly regulated by either ubiquitous and tissue specific transcription factors. It controls the intracellular redox state by inhibiting the reactive oxygen species production
-
-
-
additional information
?
-
-
ntg1 possesses N-glycosylase/AP lyase activity that allows recognition and repair of oxidative base damage (primarily of pyrimidines) as well as abasic sites, ntg2 possesses N-glycosylase/AP lyase activity that allows recognition and repair of oxidative base damage (primarily of pyrimidines) as well as abasic sites
-
-
-
additional information
?
-
-
overexpressing wild-type Ape1 attentuates all the toxic effects of cisplatin in cells containing normal endogenous levels of Ape1 and in cells with reduced Ape1 levels after Ape1siRNA treatment
-
-
-
additional information
?
-
-
overexpression of APE1/Ref-1 suppressed angiotensin II induced production of superoxide and hydrogen peroxide
-
-
-
additional information
?
-
-
reducing expression of Ape1 in neuronal cultures using small interfering RNA enhances cisplatin-induced cell killing, apoptosis, ROS generation and cisplatin-induced reduction in iCGRP release
-
-
-
additional information
?
-
-
regulation of APEX1 expression by S-adenosylmethionine, which may be one of the mechanisms of hepatocellular carconom formation
-
-
-
additional information
?
-
-
small interfering RNA knockdown of endogenous APE1 impairs high-mobility group box 1-mediated cytokine expression and MAPK activation in THP-1 cells. High-mobility group box 1-stimulation induces the translocation of APE1 to the nucleus of the cell
-
-
-
additional information
?
-
-
The BK-Ca current in APE1/Ref-1-overexpressing human umbilical vein endothelial cells is similarly inhibited by angiotensin II, except that inhibition of 43.06% is achieved using only 10 nM angiotensin II
-
-
-
additional information
?
-
-
the DNA-binding ability of NF-kappaB in the Ape1/Ref-1 expressing cells is significantly increased
-
-
-
additional information
?
-
-
the key function is to produce a 3' OH terminus that serves as a primer for repair synthesis.
-
-
-
additional information
?
-
-
ubiquitously expressed protein that functions as both an endonuclease in the repair of oxidatively damaged DNA and an aid in the binding of redox-sensitive transcription factors
-
-
-
additional information
?
-
-
When APE1 and DNA polymerase beta are both present, a ternary complex APE1-DNA polymerase beta-DNA is formed with the highest efficiency with DNA product of APE1 endonuclease activity and with DNA containing 5'-flap or mononucleotide-gapped DNA with 5'-p group
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
stimulates
Ca2+
-
optimal concentration at 5-30 mM, only 50% activity at 40 mM
Co2+
-
stimulation
Co2+
-
CoCl2 (500 microM) is essential for AP endonuclease assay. Effects of Co on APE/Ref-1 are concentration dependent
Co2+
-
0.1-1.0 mM, strong stimulation of all DNA repair activities
Fe
-
pro-inflammatory activity of iron in the lung injury, at least in part, because of its induction of APE/Ref-1
Fe2+
-
Fe2+ is able to support the incision activity of the enzyme at excess protein to DNA ratios of at least 6:1, Mg2+ and Fe2+ compete for the same metal-binding site
Fe2+
Q5KX27
EndoIV contains two Fe2+ ions and one Zn2+ ion, crystallography data. Fe2+(1) is coordinated by Glu145, Asp179, His214, Glu259, and Fe2+(2) is coordinated by His69, His110 and Glu145
Fe2+
-
0.1-1.0 mM, strong stimulation of all DNA repair activities
Iron
-
native enzyme contains a single [4Fe-4S] cluster in the 2+ oxidation state with a net spin of zero
Iron
-
[4Fe-4S] cluster is not directly involved in catalytic mechanism and therefore has most likely a structural role
Iron
-
iron-sulfur protein
Iron
P78549
[4Fe-4S]-cluster; iron-sulfur protein
Iron
-
Scr2 but not Scr1 is an iron-sulfur protein
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.
K+
-
both MgCl2 and KCl strongly influence the efficiency of Ape1 as an ssDNA or dsDNA AP endonuclease
K+
-
K+ significantly stimulates recombinant APE1 activity at 20 mM by approximately 1.3fold (compared with the absence of K+)
KCl
-
slight stimulation at 10 to 30 mM, inhibition above 100 mM
KCl
-
enzyme form A: optimal activity in 20 mM NaCl or KCl, enzyme form B: more active without salt
KCl
-
optimal concentration: 100 mM
KCl
-
optimal concentration: 125 mM; stimulates
KCl
-
optimal concentration: 0.05-0.1 M, activity against apurinic and apyrimidinic sites, 50% inhibition at 0.02 and 0.12 M; optimal concentration: 0.10 M, activity against OsO4-sites, 50% inhibition at 0.05 and 0.15 M; stimulates
KCl
-
optimal concentration: 50 mM,90% inhibition at 200 mM; stimulates
KCl
-
optimal concentration: 25-50 mM; stimulates
KCl
-
maximal AP endonuclease activity at 25-200 mM, nucleotide incision repair activity decreases dramatically above 50 mM
KCl
-
optimum concentration 50-100 mM
KCl
P28352
optimum concentration 50-100 mM
KCl
-
optimum concentration 20 mM
Mg2+
-
Mg2+ or Mn2+ required
Mg2+
-
Mg2+ or Mn2+ required; optimal concentration: 5-10 mM
Mg2+
-
Mg2+ or Mn2+ required
Mg2+
-
stimulates
Mg2+
-
optimal concentration: 1-5 mM; stimulates
Mg2+
-
Mg2+ or Mn2+ required; optimal concentration: 10 mM
Mg2+
-
required
Mg2+
-
stimulates
Mg2+
-
optimal concentration: 3 mM; required
Mg2+
-
endonuclease A does not require Mg2+ for full activity; endonuclease B has an absolute requirement for Mg2+
Mg2+
-
optimal concentration: 2 mM (endonuclease D4); optimal concentration: 4 mM for endonuclease D1 and D2; optimal concentration: 6 mM, endonuclease E; optimal concentration: 8 mM, endonuclease D3; required
Mg2+
-
optimal concentration: 20 mM; required
Mg2+
-
Mg2+ or Mn2+ required, Mg2+ better than Mn2+
Mg2+
-
optimal concentration: 4-5 mM; stimulates
Mg2+
-
required
Mg2+
-
required
Mg2+
-
repair of 5-OH-C opposite guanine is stimulated 2-fold with increasing concentrations, 5-OH-C paired with adenine is poorly repaired with increasing Mg2+ concentrations, no incision of 5-OH-C opposite adenine above 15 mM Mg2+
Mg2+
-
optimal concentration: 2.5-30 mM; stimulates
Mg2+
-
required
Mg2+
-
activity against abasic sites in single-stranded DNA
Mg2+
-
the standard reaction buffer used for the nuclease assay is supplemented with 15 mM MgCl2
Mg2+
-
the optimized buffer used for the endonuclease assay contains 5 mM MgCl2
Mg2+
-
-
Mg2+
-
APE1 binds to AP sites in the absence of Mg2+, a condition in which APE1 does not have endonuclease activity
Mg2+
-
5 mM included in assay medium, required divalent cation
Mg2+
-
2 mM included in assay medium
Mg2+
-
binds to APE1 and a functional APE1-substrate DNA complex with an overall stoichiometry of one Mg2+ per mole of APE1, the chemistry central to the function of APE1 is water activated by a Mg2+ ion, Mg2+ binding is an absolute requirement for the endonucleolytic activity
Mg2+
-
included in assay medium
Mg2+
-
In presence of Mg2+, ATP has complex effects on Ape1 cleavage activity. Endo- and exonuclease activity of Ape1 is found to be influenced by the MgCl2 concentration, with optimal exonuclease activity at low MgCl2 concentration (0.1-2 mM) and optimal endonuclease activity at high MgCl2 concentration (10-15 mM).
Mg2+
-
Mg2+, with potential binding sites A and B, binds at the B site of wild-type APE1-substrate complex and moves to the A site after cleavage occurs
Mg2+
-
APE1 reaches a maximum of 3'-phosphoglycolate excision activity at Mg2+ concentrations around 2.5 mM, APE1 mutant D70A reaches maximum activity at higher metal concentrations. In case of a THF-containing oligonucleotide as substrate, APE1 exhibits the highest AP endonuclease activity at 5 mM of metal while the specific activity of APE1 mutant D70A did not reach a maximum until 40 mM of Mg2+ is added to the reaction.
Mg2+
-
LMAP mutant A138D reaches a maximum of 3'-PG excision activity at Mg2+ concentrations around 2.5 mM, wild-type enzyme reaches maximum activity at higher metal concentrations. In case of a THF-containing oligonucleotide as substrate, the parasite enzymes LMAP and LMAPA138D, obtains the activity peaks at different magnesium concentrations (10 and 2.5 mM).
Mg2+
-
ion concentrations ranging from 0.2 to 2 mM Mg2+ promotes catalysis, APE1 is enhanced approximately 2fold (compared with the absence of Mg2+) in the presence of 2 mM Mg2+
Mg2+
-
required for APE1-catalyzed endonuclease activity
Mg2+
Q8U437
maximally stimulated at 10 mM
Mg2+
F6KAZ5
APN is active in presence and in absence of Mg2+
Mg2+
-
both the endoribonuclease and the ssRNA apurinic/apyrimidinic site cleavage activities of wild-type APE1 are present in the absence of Mg2+, while ssDNA apurinic/apyrimidinic site cleavage requires Mg2+, optimally at 0.5-2.0 mM
Mg2+
-
or Mn2+, absolutely required
Mg2+
-
required. Increasing the Mg2+ concentration alters the ratio of turns to beta-strands, and this change may be associated with the conformational changes required to achieve an active state
Mg2+
P28352
required. Increasing the Mg2+ concentration alters the ratio of turns to beta-strands, and this change may be associated with the conformational changes required to achieve an active state
MgCl2
-
tetrahydrofuran*G incision is efficiently catalyzed at 0.001 mM Mg2+, 5 mM MgCl2 are required for optimal AP endonuclease activity
Mn2+
-
Mn2+ or Mg2+ required
Mn2+
-
Mn2+ or Mg2+ required
Mn2+
-
stimulates
Mn2+
-
stimulates
Mn2+
-
10-20 mM; Mn2+ or Mg2+ required
Mn2+
-
stimulates
Mn2+
-
1 mM; partial stimulation
Mn2+
-
Mn2+ or Mg2+ required
Mn2+
-
optimum: 4-5 mM; stimulates
Mn2+
-
can only partially replace Mg2+
Mn2+
-
Glu in amino acid position 96 binds to the divalent cation
Mn2+
-
In order to cleave phosphodiester bonds in the course of endonuclease and exonuclease reactions catalyzed by APE1, Mg2+ or Mn2+ is needed
Mn2+
-
active site
Mn2+
-
divalent metal content
Mn2+
Q8U437
maximally stimulated at 10 mM
Mn2+
-
or Mg2+, absolutely required
Na+
-
65 mM included in assay medium
NaCl
-
slight stimulation at 10 to 30 mM, inhibition above 100 mM
NaCl
-
50 mM, 50% stimulation
NaCl
-
enzyme form A: optimal activity in 20 mM NaCl or KCl, enzyme form B: more active without salt
NaCl
-
optimal concentration: 50 mM; stimulates
NaCl
-
50 mM: slight stimulation, 500 mM: complete inhibition
NaCl
-
optimal concentration: 25-50 mM; stimulates
NaCl
-
150 mM, higher concentrations inhibit
Sm2+
-
the divalent metal ion soaked with the protein crystals is found specifically to associate with the glutamate residue
Zn2+
-
no effect
Zn2+
-
stimulation half as effective as with Mg2+
Zn2+
P50465
-
Zn2+
-
the optimized buffer used for the exonuclease assay contains 5 mM ZnCl2
Zn2+
-
Divalent metal content, Zn3-site mutations result in major activity loss, whereas Zn1 and Zn2 ligand mutations cause low to severe loss of catalytic efficiency. In the DNA-free wild-type enzyme structure, two metal ions (Zn1 and Zn2) are partially buried from solvent and bind a bridging hydroxide anion. The third metal ion (Zn3) is mostly solvent accessible, is distant from Zn1 and Zn2 and ligates a tightly bound water molecule to complete its coordination shell
Zn2+
Q5KX27
EndoIV contains two Fe2+ ions and one Zn2+ ion, crystallography data. The Zn2+ ion is coordinated by His182, Asp227, His229
Mn2+
-
0.1-1.0 mM, strong stimulation of all DNA repair activities
additional information
-
presence of divalent cations does not stimulate the activity
additional information
-
Mn2+ has no effect
additional information
-
equal or higher activity for Zn2+ or Mn2+- containing Endo IV suggests that one site may favor Mn2+ over Zn2+
additional information
-
cleavage of abasic DNA by UL30 occurs in the presence of EDTA and is independent of Mg2+, UL30 is 10fold less active
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(pA)10
-
-
(pA)10*d(pT)10
-
-
-
(pA)11*d(pT)11
-
-
-
(pA)12
-
-
-
(pA)16
-
-
-
(pA)16*d(pT)16
-
-
-
(pA)2
-
-
(pA)3
-
-
(pA)4
-
-
(pA)4*d(pT)4
-
-
-
(pA)6
-
-
(pA)6*d(pT)6
-
-
-
(pA)8
-
-
(pA)8*d(pT)8
-
-
-
(pA)9
-
-
(pC)10
-
-
(pC)14
-
-
-
(pC)2
-
-
(pC)4
-
-
(pC)6
-
-
(pC)8
-
-
(pU)10
-
-
(pU)10*(pA)10
-
-
-
(pU)11
-
-
-
(pU)16
-
-
-
(pU)16*(pA)16
-
-
-
(pU)4
-
-
(pU)4*(pA)4
-
-
-
(pU)6
-
-
(pU)6*(pA)6
-
-
-
(pU)8
-
-
(pU)9
-
-
(pU)9*(pA)9
-
-
-
1-methyl-4-[(1E)-1-[2-(6-methyl[1,3]dioxolo[4,5-g]quinolin-8-yl)hydrazinylidene]ethyl]-2-phenyl-1,2-dihydro-3H-pyrazol-3-one
-
inhibitor induces time-dependent increases in the accumulation of abasic sites in cells at levels that correlate with its potency to inhibit APE-1 endonuclease excision. The inhibitor also potentiates by 5fold the toxicity of a DNA methylating agent that creates abasic sites
2,2'-(2-oxo-1H-benzimidazole-1,3(2H)-diyl)diacetic acid
-
-
2,2'-(3,7-dioxo-5,7-dihydro-1H,3H-benzo[1,2-c:4,5-c']difuran-1,5-diyl)diacetic acid
-
-
2,2'-[(2,5-dimethylfuran-3,4-diyl)bis(carbonylimino)]diacetic acid
-
-
2,2'-[(6-oxo-6H-benzo[c]chromene-1,3-diyl)bis(oxy)]dipropanoic acid
-
-
2,2'-[(6-phenylpyrimidine-2,4-diyl)disulfanediyl]diacetic acid
-
-
2,2'-[butane-1,4-diylbis(1H-benzimidazole-2,1-diyl)]diacetic acid
-
-
2,4,9-trimethylbenzo[b][1,8]naphthyridin-5-amine
-
i.e. Ape1 repair inhibitor 03, specific inhibitor of AP endonuclease
2-((Z)-2-oxo-3-(4-oxo-2-thioxothiazolidin-5-ylidene)indolin-1-yl)acetic acid
-
potent inhibitory activity
2-(4-(2,5-dimethyl-1H-prryol-1-yl)phenoxy) acetic acid
-
i.e. Ape1 repair inhibitor 01, specific inhibitor of AP endonuclease
2-(5-((2-(2-carboxyphenyl)-1,3-dioxo)-2,3-dihydro-1H-isoindol-5-yl)carbonyl}-1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)benzoic acid
-
potent inhibitory activity
2-mercaptoethanol
O15527
suppresses delta-elimination partially
2-[(5Z)-5-[1-(carboxymethyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
-
-
3,3'-(1,3,4-thiadiazole-2,5-diyldisulfanediyl)dipropanoic acid
-
-
3,3'-(2-thioxo-1H-benzimidazole-1,3(2H)-diyl)dipropanoic acid
-
-
3-((3,4-dimethylphenoxy)methyl)furan-2-carboxylic acid
-
-
3-((pyridin-2-ylthio)methyl)benzofuran-2-carboxylic acid
-
-
3-(1-(carboxymethyl)-5-(4-chlorophenyl)-1H-pyrrol-2-yl)propanoic acid
-
potent inhibitory activity
3-(1-(carboxymethyl)-5-(4-fluorophenyl)-1H-pyrrol-2-yl)propanoic acid
-
potent inhibitory activity
3-(1-(carboxymethyl)-5-(thiophen-2-yl)-1H-pyrrol-2-yl)propanoic acid
-
potent inhibitory activity
3-(1-(carboxymethyl)-5-p-tolyl-1H-pyrrol-2-yl)propanoic acid
-
-
3-(2-carboxyethyl)-4-hydroxyquinoline-6-carboxylic acid
-
-
3-(5-((E)-(3-(carboxymethyl)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl)furan-2-yl)benzoic acid
-
potent inhibitory activity
3-[(4Z)-4-[1-(carboxymethyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-5-oxo-2-thioxoimidazolidin-1-yl]propanoic acid
-
-
3-[(6-amino-9H-purin-8-yl)sulfanyl]propanoic acid
-
-
3-[5-(2,3-dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2-propionic acid
P27695
E3330 specifically blocking the APE1 redox but not DNA activity, an equilibrium constant (KD) of 1.6 nM is obtained for the binding of E3330 to APE1. E3330 is also shown to block the ability of APE1 to reduce NF-kappaB, thus interfering with the redox activity of APE1
3-[[4-(carboxymethyl)benzyl]sulfanyl]-8-methyl-5H-[1,2,4]triazino[5,6-b]indole-5-carboxylic acid
-
-
4-((2-carboxyphenoxy)methyl)-2,5-dimethylfuran-3-carboxylic acid
-
potent inhibitory activity
4-(2,6,8-trimethylquinolin-4-ylamino)phenol
-
i.e. Ape1 repair inhibitor 02, specific inhibitor of AP endonuclease
4-(4-(4-carboxyphenoxy)phenylsulfonyl)benzene-1,2-dioic acid
-
-
4-(4-(4-carboxyphenylsulfonyl)phenyl)sulfanylbenzene-1,2-dioic acid
-
potent inhibitory activity
4-(4-(4-carboxyphenylthio)phenylsulfonyl)benzene-1,2-dioic acid
-
potent inhibitory activity
4-([[(3-carboxy-5-methylfuran-2-yl)methyl]sulfanyl]methyl)-5-methylfuran-2-carboxylic acid
-
-
4-chloromercuribenzoate
-
complete inhibition at 1 mM
4-chloromercuribenzoate
-
complete inhibition at 2 mM
4-chloromercuribenzoate
-
complete inhibition at 1 mM
4-[(4Z)-4-[1-(carboxymethyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-5-oxo-2-thioxoimidazolidin-1-yl]butanoic acid
-
-
4-[[(2-carboxypropyl)sulfanyl]methyl]-5-methylfuran-2-carboxylic acid
-
-
5,5'-[methanediylbis(sulfanediylmethanediyl)]bis(2-methylfuran-3-carboxylic acid)
-
-
5-(((tetrahydrofuran-2-yl)methylthio)methyl)-2-methylfuran-3-carboxylic acid
-
-
5-([[(4-carboxy-5-methylfuran-2-yl)methyl]sulfanyl]methyl)-3-methylfuran-2-carboxylic acid
-
-
6-hydroxy-DL-DOPA
-
complete inhibition at 0.1 mM
7-nitro-1H-indole 2-carboxylic acid
-
CRT0044876, binds to the active site of APE/Ref-1 and effectively inhibits its AP endonuclease, 3'-phosphodiesterase and 3'-phosphatase activities at low micromolar concentrations
7-nitro-1H-indole-2-carboxylic acid
-
CRT0044876
8-[(2E)-2-(3-methoxybenzylidene)hydrazinyl]-6-methyl[1,3]dioxolo[4,5-g]quinoline
-
inhibitor induces time-dependent increases in the accumulation of abasic sites in cells at levels that correlate with its potency to inhibit APE-1 endonuclease excision. The inhibitor also potentiates by 5fold the toxicity of a DNA methylating agent that creates abasic sites
8-[(2E)-2-[(9-ethyl-9H-carbazol-3-yl)methylidene]hydrazinyl]-6-methyl[1,3]dioxolo[4,5-g]quinoline
-
inhibitor induces time-dependent increases in the accumulation of abasic sites in cells at levels that correlate with its potency to inhibit APE-1 endonuclease excision. The inhibitor also potentiates by 5fold the toxicity of a DNA methylating agent that creates abasic sites
A1NI2-A3NI1
-
-
Acridine dimers
-
with a spermidine linker
-
adenine
-
50% inhibition at 0.2 mM
ATP
-
in presence of 1 mM Mg2+, Ape1 incision activity is inhibited at higher ATP concentrations (2-5 mM). Depending on the relative concentration of Mg2+, ATP can have both inhibitory and stimulatory consequences on Ape1 incision capacity
aurintricarboxylic acid
-
potent inhibitor of APE1
beta-mercaptoethanol
-
complete inhibition at 10 mM and higher
Ca2+
-
39% inhibition at 10 mM
Ca2+
-
complete inhibition at 2 mM
Ca2+
-
50% activity at 40 mM
Ca2+
-
50% inhibition at 5-10 mM
Ca2+
-
5-10 mM, inhibitory
ceftriaxone sodium
-
-
cephapirin sodium
-
-
Co2+
-
86% inhibition at 10 mM
Cu2+
-
90% inhibition at 10 mM
cycloheximide
-
treatment decreases APEX1 protein levels as compared with untreated mouse hepatocytes
d(p((3-hydroxytetrahydrofuran-2-yl)methyl phosphate))
-
-
d(p(2,3-dihydroxy-5-oxopentyl phosphate))
-
-
d(pA)10
-
-
d(pA)10*d(pT)10
-
-
-
d(pA)12
-
-
d(pA)12*d(pT)12
-
-
-
d(pA)14
-
-
d(pA)14*d(pT)14
-
-
-
d(pA)16
-
-
d(pA)16*d(pT)16
-
-
-
d(pA)2
-
-
d(pA)2*d(pT)2
-
-
-
d(pA)20*(pT)20
-
-
-
d(pA)4
-
-
d(pA)4*d(pT)4
-
-
-
d(pA)6
-
-
d(pA)6*d(pT)6
-
-
-
d(pA)8
-
-
d(pA)8*d(pT)8
-
-
-
d(pC)10
-
-
d(pC)11
-
-
-
d(pC)13
-
-
-
d(pC)2
-
-
d(pC)3
-
-
d(pC)5
-
-
d(pC)7
-
-
d(pC)9
-
-
d(pG)2
-
-
d(pG)4
-
-
d(pG)6
-
-
d(pG)8
-
-
d(pT)10
-
-
d(pT)11
-
-
-
d(pT)12
-
-
-
d(pT)14
-
-
-
d(pT)15
-
-
-
d(pT)2
-
-
d(pT)3
-
-
d(pT)4
-
-
d(pT)6
-
-
d(pT)8
-
-
dAMP
-
-
dCMP
-
-
dGMP
-
-
dithiothreitol
-
at 1 mM and higher dithiothreitol concentrations AP site incision is strongly inhibited with less than 10% of the activity remaining, the inhibition by dithiothreitol is reverted by H2O2 in a dose-dependent manner, the inhibition by dithiothreitol is not reverted by divalent cations, including Zn2+, Co2+, Ca2+, and Ni+
dTMP
-
-
d[(p((3-hydroxytetrahydrofuran-2-yl)methyl phosphate))3pT]
-
-
d[(p((3-hydroxytetrahydrofuran-2-yl)methyl phosphate))5pT]
-
-
d[(p((3-hydroxytetrahydrofuran-2-yl)methyl phosphate))7pT]
-
-
d[(p((3-hydroxytetrahydrofuran-2-yl)methyl phosphate))9pT]
-
-
E3330
-
binds specifically to Ape1/Ref-1 and blocks its redox activity
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
E3330
-
forms a reversible adduct with DELTA40APE1, an N-terminal truncation of APE1 including residues 40-318. E3330 also increases the extent of disulfide bond formation involving redox critical Cys residues in APE1
EDTA
-
96% inhibition at 20 mM
EDTA
-
no inhibition
EDTA
-
complete inhibition at 20 mM
EDTA
-
complete inhibition at 5 mM
EDTA
-
no inhibition
EDTA
-
no inhibition
EDTA
-
-
EDTA
-
complete inhibition at 2 mM
EDTA
-
90% inhibition at 0.1 mM
EDTA
O15922
incision activity is completely abolished when 10 mM EDTA is added to the reaction
EDTA
-
complete inhibition at 1 mM
Fe2+
-
inhibitory effects on APE/Ref-1 activity
granzyme A
-
granzyme A cleaves APE1 at Lys31 and inactivates it
-
Harmane
-
i.e. 1-methyl-9H-pyrido-[3,4-b]indole, inhibits Escherichia coli endonuclease III and its associated dihydroxythymidine-DNA glycosylase activity, 50% inhibition at 0.4 mM, 80% inhibition at 1 mM
Harmane
-
i.e. 1-methyl-9H-pyrido-[3,4-b]indole, only slight inhibition of AP endocunlease I and II
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
K+
-
K+ is inhibitory to the native APE1 at 0.2-10 mM with approximately 5fold inhibition
Kainic acid
-
APE/Ref-1 is decreased by kainic acid injury in a time-dependent manner at the level of proteins, not transcripts
KCl
-
inhibition above 100 mM, 5fold inhibition at 500 mM
KCl
-
50 mM: 70% inhibition
KCl
-
maximal AP endonuclease activity at 25-200 mM, nucleotide incision repair activity decreases dramatically above 50 mM
KCl
-
varying concentrations of KCl show an initial decrease followed by a significant increase in KD value for the APE/AP DNA binding
lucanthone
-
inhibits repair activity from cellular extracts and enhances cell killing effect of the laboratory alkylating agent methyl methanesulfonate and the clinically relevant agent temozolomide, no inhibition of redox function or exonuclease activity on mismatched nucleotides
methoxamine
T1SGV2, T1SHD4
;
-
Mg2+
-
MgCl2 above 10 mM
Mg2+
-
57% inhibition at 10 mM
Mg2+
-
MgCl2 above 20 mM
Mg2+
-
selectively inhibits endonuclease III activity when apurinic/apyrimidinic DNA is used as substrate, but has no effect when DNA containing either urea or thymine glycol is used as substrate
Mg2+
-
50% inhibition at 5-10 mM
Mg2+
-
AP-endonuclease activity of the C99S mutant as well as of the double mutants C138S/C99S and C65S/C99S is strongly inhibits in the presence of 10 mM Mg2+. Increasing Mg2+ concentration to 10 mM inhibited product formation by 5.4-fold. At 20 mM Mg2+, the product formation with wild-type APE1 is inhibited 4.2-fold and with the C99S mutant 14-fold relative to the activity of the wild-type protein in 5 mM Mg2+
Mg2+
-
In case of APE 1, the excision being severely inhibited (below 25%) at 10 mM and higher ion concentrations. APE1 mutant D70A is more refractory to Mg2+ inhibition, thus still retaining about 50% of activity at 20 mM Mg2+. In case of a THF-containing oligonucleotide as substrate, inhibition is not evidenced until 80mM is reached.
Mg2+
-
In case of LMAP mutant A138D, the excision being severely inhibited (below 25%) at 10 mM and higher ion concentrations. Wild-type enzyme is more refractory to Mg2+ inhibition, thus still retaining about 50% of activity at 20 mM Mg2+
Mg2+
-
10-20 mM Mg2+ is inhibitory to the RNA-cleaving activity of APE1
Mg2+
-
5-10 mM, inhibitory
MgCl2
-
tetrahydrofuran*G incision activity is inhibited above 2 mM
Mitoxantrone
-
-
Mn2+
-
37% inhibition at 10 mM
myricetin
-
above 80% inhibition at 0.1 mM
N-(3-chlorophenyl)-5,6-dihyro-4H-cyclopenta[d]isoxazole-3-carboxamide
-
i.e. Ape1 repair inhibitor 06, specific inhibitor of AP endonuclease
N-ethylmaleimide
-
-
N-ethylmaleimide
-
-
N-ethylmaleimide
-
treatment of fully denatured full-length APE1 and DELTA40APE1, an N-terminal truncation of APE1 including residues 40-318, results in modification of 7 and 2 resiudes, respectively
NaCl
-
complete inhibition at 1 M, 40% inhibition at 0.5 M
NaCl
-
inhibition above 100 mM, 5fold inhibition at 500 mM
NaCl
-
above 10 mM
NaCl
-
above 0.15 M
NaCl
-
above 10 mM; complete inhibition at 500 mM
NaCl
-
above 50 mM: slight stimulation, 500 mM: complete inhibition
NaCl
-
50% inhibition by 50 mM
NaCl
-
1 mM: complete inhibition
NaCl
-
50 mM: 70% inhibition
NaCl
-
inhibition above 50 mM
NaCl
-
inhibition above 150 mM
NaCl
O29876
catalytic activity is inhibited in buffer more than 100 mM NaCl
NaH2PO4
-
-
NSC-13755
-
complete inhibition at 0.1 mM
oligonucleotide containing 2'-fluorinated 5R- or 5S-thymidine glycol
-
inhibits DNA glycosylase activity, not the AP lyase step, in the Endo III reaction, by stabilizing the glycosidic bond
-
P53
-
after camptothecin treatment, p53 is a negative regulator of APE1 expression, APE1 promoter activity is repressed by wild-type p53, but not by mutant p53
Pb2+
-
inhibitory effects on APE/Ref-1 activity
PNRI-299
-
inhibition on AP-1 transcription
polyinosinic-polycytidylic acid
-
transfection of APE1 suppresses the extracellular release of high-mobility group box 1 in response to polyinosinic-polycytidylic acid stimulation
-
proteinBcl2
-
overexpression of Bcl2, a major cellular oncogenic protein, in cells reduces formation of the APE1-XRCC1 complex, Bcl2 not only prolongs cell survival but also suppresses the repair of abasic (AP) sites of DNA lesions. Bcl2 directly interacts with APE1 via its BH domains, and deletion of any of the BH domains from Bcl2 results in loss of the ability of Bcl2 to suppress APE1 endonuclease activity and AP site repair
-
Reactive blue 2
-
above 80% inhibition at 0.1 mM
reactive oxygen species
-
reactive oxygen species not only can inhibit APE/Ref-1 activities by direct oxidation of amino acid residues, but also affects the expression level and subcellular localization of APE/Ref-1
-
resveratrol
-
dock into one of the two drug-treatable pockets located in the redox domain
RPA proteins
P27695
RPA proteins are able to suppress the APE1 endonuclease activity in ssDNA of a replicative fork but not in a transcription bubble or in dsDNA
-
Sodium citrate
-
-
Triton X-100
-
increases activity of nuclear membrane enzyme, activity of nuclear sap and chromatin non-histone enzyme untouched or decreased
tyrphostin AG 538
-
mild inhibition at 0.1 mM
Zn2+
-
strong inhibitor
Zn2+
-
86% inhibition at 10 mM
[(3Z)-3-(3-[[(2-hydroxyphenyl)carbonyl]amino]-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)-2-oxo-2,3-dihydro-1H-indol-1-yl]acetic acid
-
-
[(3Z)-3-[3-(4-bromophenyl)-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene]-2-oxo-2,3-dihydro-1H-indol-1-yl]acetic acid
-
-
[(5Z)-5-[1-(carboxymethyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
-
Mn2+
-
50% inhibition at 5-10 mM
additional information
-
inhibition at high ionic strength, factor 5 at 500 mM
-
additional information
-
no inhibition by N-ethylmaleimide
-
additional information
-
-
-
additional information
-
5-OH-C paired with adenine was poorly repaired with increasing Mg2+ concentrations, no incision of 5-OH-C opposite adenine above 15 mM Mg2+
-
additional information
-
enzyme is inhibited by the product of its DNA N-glycosylase activity directed against Tg:G, the AP:G site, but not inhibited by the AP:A site arising from release of Tg from Tg:A
-
additional information
-
in contrast to activity against abasic sites in souble-stranded DNA the enzyme does not display product inhibition when acting on absic sites in single-stranded DNA
-
additional information
-
the enzyme activity of apurinic/apyrimidinic endonuclease is blocked by APE-specific siRNAs
-
additional information
-
APE1 silencing via siRNA transfection inhibits both the nuclear and cytoplasmic expression of APE1
-
additional information
-
exposing neuronal cultures to Api1 small interfering RNA significantly reduces the expression of Api1
-
additional information
-
methoxyamine binds to and occludes abasic sites in DNA and thereby inhibits Ape1/Ref-1-mediated DNA repair
-
additional information
-
hiolactomycin and methyl 3,4-dephostatin have no effect on total AP site cleavage activity
-
additional information
-
the presence within the G quadruplex DNA structure of an abasic site decreases the efficiency of human AP endonuclease activity. This effect is mostly the result of a decreased enzymatic activity and not of decreased binding of the enzyme to the damaged site
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
8-oxoguanine-DNA glycosylase
-
OGG1 stimulates the hydrolytic activity of AP endonuclease
-
APE1
-
APE1, a human homolog of Escherichia coli exonuclease III Xth stimulates under conditions of Vmax
-
ATP
-
in presence of 1 mM Mg2+, Ape1 abasic endonuclease activity is stimulated (1.75- and 1.25-fold at 0.5 and 1 mM ATP concentrations). At 10 mM MgCl2, the higher concentrations of ATP has stimulatory effects on AP site incision by Ape1
cisplatin
-
cisplatin-induced (chemotherapeutic agent) increase in Api1 expression after exposition with 25 micromol/l or higher concentrations for 24 hours, Api1 is neuroprotective against cisplatin-induced neurotoxity
cisplatin
-
2fold increase in Y-box-binding protein-1/hNTH1 complex formation in transfected MCF-7 cells after a treatment of 12 microM cisplatin for 4 h
cockayne syndrome B protein
-
CSB protein stimulates the AP site incision activity of APE1
-
cockayne syndrome B protein
P27695
cockayne syndrome B protein potentiates the APE1 activity on fully paired AP-DNA but much more on bubble AP-DNA, suggesting a role for this protein in the transcription-repair pathway
-
dithiothreitol
-
stimulates over 100% at 1 mM
DNA-dependent ATPase CSB
-
in presence of 1 mM Mg2+, enzyme stimulates AP site incision by Ape1 in the absence of ATP on both fully paired duplex DNA (42F-42Comp) and an 11-nt bubble duplex substrate containing a centrally located abasic site (42F-42bubbleComp). When 2.5 mM ATP is included in the reactions with 1 mM MgCl2, inhibition of Ape1 incision activity is detected
-
Helicobacter pylori (CagA+) water-extract protein (HPWEP)
-
HPWEP-stimulation significantly increases APE-1 mRNA expression levels in human peripheral macrophages. HPWEP-stimulation increases APE-1 expression levels in AGS cells. HPWEP stimulation increases APE-1 protein expression in gastric epithelial MKN-28 cells in a dose-dependent manner (1:30 and 1:10 dilution). When normalized to beta-actin, HPWEP stimulation at a 1:10 dilution significantly increases APE-1 protein expression compared to control MKN-28 cells. APE-1 protein expression is further increased in HPWEP (1:10 dilution) stimulated MKN-28 cells after treatment with hypo/reoxygenation.
-
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
-
imidazole
-
enhances activity of wild-type enzyme markedly, enhances Y171A somewhat and fails to enhance Y171F. When stoichiometric levels of tyrosine are included in the reaction with imidazole, wild-type enzyme as well as mutant enzymes are stimulated. Degree of stimulation of wild-type enzyme continues to exceed that of the mutants
KCl
-
varying concentrations of KCl show an initial decrease followed by a significant increase in KD value for the APE/AP DNA binding
NaCl
Q8U437
the highest AP endonuclease activity is observed at NaCl concentrations of 100-150 mM
oxidative stress
-
-
-
S-adenosylmethionine
-
S-adenosylmethionine co-treatment is able to increase APEX1 protein levels
Triton X-100
-
increases activity of nuclear membrane enzyme, activity of nuclear sap and chromatin non-histone enzyme untouched or decreased
Triton X-100
-
no stimulation
Triton X-100
-
20-50% stimulation at 0.03%
UV light
-
3fold increase in Y-box-binding protein-1/hNTH1 complex formation in transfected MCF-7 cells after a treatment with a UV irradiation dose of 40 J/m2 tested for 4 h
-
Y-box-binding protein-1
-
protein strongly stimulates in vitro the activity of hNTH1 toward DNA duplex probes containing oxidized bases, lesions prone to be present in cisplatin treated cells
-
lipopolysaccharide
-
100 ng/ml lipopolysaccharide stimulates the upregulation and nuclear translocation of APE1 in activated macrophages. APE1 critically mediates both the translocation of NF-B to the nucleus and the expression of inducible nitric oxide synthase by murine macrophage RAW264.7 cells after stimulation with LPS
additional information
-
oxidative stress enhances enzyme activity by activation of the APE promoter
-
additional information
P27695
APE1 functional activation is a consequence of different stimuli (UV light, hypoxia, ischemia/reperfusion, hypxic-ischemic insult, Helicobacter pylori infection, reactive oxygen species, atherosclerotic plaque, TSH, CD40 triggering, P2Y triggering, cysteamine-induced duodenal ulceration, Pb asbestos, intracellular Ca2+) that generate both physiological and toxic oxidative stress conditions or increase the intracellular cAMP levels leading to different outcomes; expression is altered in several metabolic and proliferative disorders such as in tumors and aging; functional triggering of membrane-bound receptors (such as those for thyrotropin, CD40L, ATP, interleukin-2) can lead to APE1 functional activation through intracellular generation of sublethal doses of reactive oxygen species
-
additional information
-
expression of AdAPE1/Ref-1 is significantly higher in cells transfected with AdAPE1/Ref-1 than in the control cells (5.3-fold) demonstrating that infection with AdAPE1/Ref-1 can significantly increase the amount of cytoplasmic APE1/Ref-1 in human umbilical vein endothelial cells
-
additional information
-
after infection with adenoviral constructs (mutant C65A) and treatment with 50 micromol/l cisplatin, Ape1 is overexpressed in sensory neuronal rat cell cultures
-
additional information
-
no increase in the amount of Y-box-binding protein-1/hNTH1 complex in transfected MCF-7 cells after camptothecin or mitomycin C treatments compared to untreated MCF7 cells
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.004
(dA)230*(dT,dU)230
-
ratio dT:dU is 15, partially depyrimidinated by uracil-DNA glycosylase, pH 8
-
0.000093
12-mer oligodeoxyribonucleotide containing a natural AP site
-
wild-type, pH 7.5, 25C
-
0.00022
12-mer oligodeoxyribonucleotide containing a natural AP site
-
mutant Y171F/P173L/N174K, pH 7.5, 25C
-
0.000098
12-mer oligodeoxyribonucleotide containing a tetrahydrofuran analogue at the natural AP site
-
wild-type, pH 7.5, 25C
-
0.000048
18-mer containing P33-labeled tetrahydrofuran
-
enzyme dephosphorylated by lambda phosphatase, pH 7.5, 22C
-
0.000081
18-mer containing P33-labeled tetrahydrofuran
-
enzyme phosphorylated by casein kinase II, pH 7.5, 22C
-
0.000098
2-deoxyribonolactone
-
pH 7.6, room temperature
0.0000262
26-bp-oligonucleotide
F6KAZ5
pH 7.5, 37C
-
0.0001792
34FDNA
-
-
-
0.001561
34FRNA
-
-
-
0.0000091
35 base pair oligonucleotide containing 5,6-dihydrouracil opposite A
-
pH 7.6, 37C, wild-type enzyme
-
0.14
35 base pair oligonucleotide containing 5,6-dihydrouracil opposite A
-
pH 7.6, 37C, mutant enzyme R184A
-
0.0000036
35 base pair oligonucleotide containing 5,6-dihydrouracil opposite G
-
pH 7.6, 37C, wild-type enzyme
-
0.000133
35 base pair oligonucleotide containing 5,6-dihydrouracil opposite G
-
pH 7.6, 37C, mutant enzyme R184A
-
0.0000097
35 base pair oligonucleotide containing 5,6-dihydroxy-5,6-dihydrothymine opposite A
-
pH 7.6, 37C, wild-type enzyme
-
0.004
35 base pair oligonucleotide containing 5,6-dihydroxy-5,6-dihydrothymine opposite A
-
pH 7.6, 37C, mutant enzyme R184A
-
0.0000059
35 base pair oligonucleotide containing 5,6-dihydroxy-5,6-dihydrothymine opposite G
-
pH 7.6, 37C, wild-type enzyme
-
0.00192
35 base pair oligonucleotide containing 5,6-dihydroxy-5,6-dihydrothymine opposite G
-
pH 7.6, 37C, mutant enzyme R184A
-
0.000011
37mer with AP/A
-
pH 6.8, 37C, Ntg1p
-
0.0000218
37mer with AP/A
-
pH 6.8, 37C, Ntg2p
-
0.000037
37mer with AP/C
-
pH 6.8, 37C, Ntg1p
-
0.000046
37mer with AP/C
-
pH 6.8, 37C, Ntg2p
-
0.0000064
37mer with AP/G
-
pH 6.8, 37C, Ntg2p
-
0.000025
37mer with AP/G
-
pH 6.8, 37C, Ntg1p
-
0.0000067
37mer with AP/T
-
pH 6.8, 37C, Ntg1p
-
0.0000094
37mer with AP/T
-
pH 6.8, 37C, Ntg2p
-
0.00016
37mer with dihydrouridine
-
pH 6.8, 37C, Scr2
-
0.000227
37mer with dihydrouridine
-
pH 6.8, 37C, Scr1
-
0.0000034
43-mer oligonucleotide containing apurinic/apyrimidinic sites
-
37C, wild-type enzyme
-
0.0000136
43-mer oligonucleotide containing apurinic/apyrimidinic sites
-
37C, mutant enzyme N226A
-
0.0000184
43-mer oligonucleotide containing apurinic/apyrimidinic sites
-
37C, mutant enzyme N229A
-
0.0000278
43-mer oligonucleotide containing apurinic/apyrimidinic sites
-
37C, mutant enzyme N226A/N229A
-
0.0000368
43-mer oligonucleotide containing the AP-site analog THF at nt 31
-
wild-type, presence of 2 mM Mg2+
-
0.0000536
43-mer oligonucleotide containing the AP-site analog THF at nt 31
-
mutant C99S, presence of 2 mM Mg2+
-
0.0000035
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
wild-type, Nei placed opposite T
0.0000066
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
wild-type, Nei placed opposite C
0.0000085
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
wild-type, Nei placed opposite G
0.000038
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant QLY/AAA, Nei placed opposite A
0.000042
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant QLY/AAA, Nei placed opposite G
0.000054
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant deltaQLY, Nei placed opposite G
0.000077
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant Q261A, Nei placed opposite G
0.00014
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant QLY/AAA, Nei placed opposite C
0.00016
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant QLY/AAA, Nei placed opposite T; wild-type, Nei placed opposite A
0.00026
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant Q261A, Nei placed opposite A
0.00027
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant Q261A, Nei placed opposite C
0.0014
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant Q261A, Nei placed opposite T
0.00058
5'-CTCTCCCTTC-8-oxo-7,8-dihydroguanine-CTCCTTTCCTCT-3'
P50465
wild-type, Nei placed opposite G
0.00061
5'-CTCTCCCTTC-8-oxo-7,8-dihydroguanine-CTCCTTTCCTCT-3'
P50465
wild-type, Nei placed opposite A
0.00068
5'-CTCTCCCTTC-8-oxo-7,8-dihydroguanine-CTCCTTTCCTCT-3'
P50465
wild-type, Nei placed opposite C
0.0013
5'-CTCTCCCTTC-8-oxo-7,8-dihydroguanine-CTCCTTTCCTCT-3'
P50465
wild-type, Nei placed opposite T
0.0000642
5'-Cy3-CAAGGTAGTrUATCCTTG-1-Black Hole Quencher1-3'
-
native enzyme
-
0.000424
5'-Cy3-CAAGGTAGTrUATCCTTG-1-Black Hole Quencher1-3'
-
recombinant enzyme
-
0.0000023
5'-GACAAGCGCAG-(5R,6S)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
wild-type, Nei placed opposite G
0.0000032
5'-GACAAGCGCAG-(5R,6S)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
wild-type, Nei placed opposite A
0.0000044
5'-GACAAGCGCAG-(5R,6S)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
wild-type, Nei placed opposite C; wild-type, Nei placed opposite T
0.000049
5'-GACAAGCGCAG-(5R,6S)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
mutant QLY/AAA, Nei placed opposite G
0.000066
5'-GACAAGCGCAG-(5R,6S)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
mutant deltaQLY, Nei placed opposite A
0.00019
5'-GACAAGCGCAG-(5R,6S)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
mutant QLY/AAA, Nei placed opposite T
0.00024
5'-GACAAGCGCAG-(5R,6S)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
mutant Q261A, Nei placed opposite G
0.0000023
5'-GACAAGCGCAG-(5S,6R)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
wild-type, Nei placed opposite G
0.0000046
5'-GACAAGCGCAG-(5S,6R)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
wild-type, Nei placed opposite T
0.0000047
5'-GACAAGCGCAG-(5S,6R)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
wild-type, Nei placed opposite C
0.000016
5'-GACAAGCGCAG-(5S,6R)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
wild-type, Nei placed opposite A
0.00021
5'-GACAAGCGCAG-(5S,6R)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
mutant Q261A, Nei placed opposite G
0.00082
5'-TCGAGGATCCTGAGCTCGAGTCGACGXTCGCGAATTCTGCGGATCCAAGC-3'
-
pH 7.5, 37C
-
0.00091
5'-TCGAGGATCCTGAGCTCGAGTCGACGXTCGCGAATTCTGCGGATCCAAGC-3'
P28352
pH 7.5, 37C
-
0.000023
5,6-dihydrothymidine/A
-
pH 7.5, 37C
0.000038
5,6-dihydrothymidine/A
-
pH 7.5, 37C
0.000026
5-hydroxy-2'-deoxyuridine/G
-
pH 7.5, 37C
-
0.000316
5-hydroxy-2'-deoxyuridine/G
-
pH 7.5, 37C
-
0.000088
AP-DNA
-
wild-type in rAP-containing oligonucleotide cleavage assay
-
0.00012
AP-DNA
-
mutant Y72F in rAP-containing oligonucleotide cleavage assay
-
0.0075
AP-DNA
-
mutant Y72A in rAP-containing oligonucleotide cleavage assay
-
0.011
AP-DNA
-
mutant R37A in rAP-containing oligonucleotide cleavage assay
-
0.0000238
AP-DNA-DNA
-
1 mM Mg2+
-
0.0000057
AP-DNA-RNA
-
1 mM Mg2+
-
0.0000213
apruinic/apyrimidinic site
-
pH 7.6, room temperature
-
0.0000027
apurinic site
-
37C, pH 8
-
0.000075 - 0.00062
apurinic site
-
dsDNA, pH 7.5, 37C
-
0.00000052
apurinic sites of DNA
-
pH 7.5, 30C
-
0.008
apurinic sites of DNA
-
-
-
0.000000083
apurinic/apyrimidinic sites
P50465
wild-type, Nei placed opposite A
-
0.00000011
apurinic/apyrimidinic sites
P50465
wild-type, Nei placed opposite G
-
0.000022
apurinic/apyrimidinic sites
P50465
mutant QLY/AAA, Nei placed opposite G
-
0.000028
apurinic/apyrimidinic sites
P50465
mutant QLY/AAA, Nei placed opposite A
-
0.0061
CAAXACCTTCATCCTTTCC
-
ssDNA, X: AP site, pH 7.5, 37C
-
0.0075
CAXAACCTTCATCCTTTCC
-
ssDNA, X: AP site, pH 7.5, 37C
-
0.013
CTAGTCAXCACTGTCTGTGGATAC
-
ssDNA, X: AP site, pH 7.5, 37C
-
0.0091
CXAAACCTTCATCCTTTCC
-
ssDNA, X = AP site, pH 7.5, 37C
-
0.00028
cytosine-labeled DNA
-
-
-
0.000103
dihydrouridine/G
-
pH 7.5, 37C
0.000884
DNA
-
LMAP mutant A138D, 3'-phosphodiesterase activity
0.001365
DNA
-
LMAP, 3'-phosphodiesterase activity
0.001587
DNA
-
APE1 mutant D70A, 3'-phosphodiesterase activity
0.001689
DNA
-
APE1, 3'-phosphodiesterase activity
0.00000007
DNA containing 5-OH-C/A
-
wild-type, pH 7.5, 37C, presence of EDTA
-
0.00000014
DNA containing 5-OH-C/A
-
P211R mutant, pH 7.5, 37C, presence of Mg2+
-
0.0000002
DNA containing 5-OH-C/A
-
P211R mutant, pH 7.5, 37C, presence of EDTA; wild-type, pH 7.5, 37C, presence of Mg2+
-
0.0000017
DNA containing 5-OH-C/A
-
G212 mutant, pH 7.5, 37C, presence of Mg2+
-
0.0000035
DNA containing 5-OH-C/A
-
G212 mutant, pH 7.5, 37C, presence of EDTA
-
0.000000048
DNA containing 5-OH-C/G
-
P211R mutant, pH 7.5, 37C, presence of Mg2+
-
0.00000005
DNA containing 5-OH-C/G
-
wild-type, pH 7.5, 37C, presence of Mg2+ or EDTA
-
0.00000009
DNA containing 5-OH-C/G
-
P211R mutant, pH 7.5, 37C, presence of EDTA
-
0.000001
DNA containing 5-OH-C/G
-
G212 mutant, pH 7.5, 37C, presence of EDTA
-
0.0000012
DNA containing 5-OH-C/G
-
G212 mutant, pH 7.5, 37C, presence of Mg2+
-
100
DNA containing an abasic site
-
pH 7.5, wild-type enzyme, low salt concentration (82 mM NaCl)
108
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y128A, high salt concentration (150 mM NaCl)
110
DNA containing an abasic site
-
pH 7.5, wild-type enzyme, high salt concentration (150 mM NaCl)
140
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y128A, low salt concentration (82 mM NaCl)
165
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y269A, low salt concentration (82 mM NaCl)
255
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y171F, low salt concentration (82 mM NaCl)
310
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y171A, high salt concentration (150 mM NaCl)
360
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y171A, low salt concentration (82 mM NaCl)
413
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y269A, high salt concentration (150 mM NaCl)
0.000069
DNA containing dihydrouracil
-
wild-type, pH 8, 37C
-
0.00017
DNA containing dihydrouracil
-
K212R mutant, pH 8, 37C
-
0.00000167
DNA containing O-benzylhydroxylamine
-
pH 7.5
-
0.00000284
DNA containing O-methylhydroxylamine
-
pH 7.5
-
0.0000002
DNA containing thymine glycol
-
pH 7.5, 30C
-
0.0000015
DNA containing thymine glycol
-
pH 7.5
-
0.00000056
DNA containing urea
-
pH 7.5, 30C
-
0.00005
DNA with 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine/C
-
pH 7.5, 37C
0.00025
DNA with 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine/C
-
pH 7.5, 37C
0.000024
double-stranded DNA with abasic sites
-
-
-
0.0000084
duplex oligonucleotide containing a 5,6-dihydro-2'-deoxyuridine*G pair
-
pH 6.8, 37C, nucleotide incison repair activity
-
0.0000072
duplex oligonucleotide containing a alpha-2'-deoxyadenosine*T pair
-
pH 6.8, 37C, nucleotide incison repair activity
-
0.0000027
duplex oligonucleotide containing a tetrahydrofuran*G pair
-
pH 6.8, 37C, nucleotide incison repair activity
-
0.00005
oligomer with G/U pair
-
D308A mutant, pH 7.5
-
0.0001
oligomer with G/U pair
-
wild-type, pH 7.5
-
0.00012
oligomer with G/U pair
-
D283A mutant, pH 7.5
-
0.00024
oligomer with G/U pair
-
D283/D308A mutant, pH 7.5
-
0.0013
oligomer with G/U pair
-
H309N mutant, pH 7.5
-
0.065
Red substrate 2
-
-
-
0.000428
single-stranded DNA with abasic sites
-
-
-
0.0000009
tetrahydrofuranyl/G
-
pH 7.5, 37C
-
0.0000013
tetrahydrofuranyl/G
-
pH 7.5, 37C
-
0.000136
THF-containing oligonucleotide
-
APE1 mutant D70A, AP endonuclease activity
-
0.000154
THF-containing oligonucleotide
-
Ape1, AP endonuclease activity
-
0.000184
THF-containing oligonucleotide
-
LMAP mutant A138D, AP endonuclease activity
-
0.0002
THF-containing oligonucleotide
-
LMAP, AP endonuclease activity
-
0.000015
thymidine-labeled DNA
-
-
-
0.00003
alkylated-depurinated DNA
-
pH 8
-
additional information
AP-DNA
-
not detected in mutant E261Q in rAP-containing oligonucleotide cleavage assay
-
0.0163
GTACGTAXCCACAGACAGTGATGA
-
ssDNA, X: AP site, pH 7.5, 37C
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
Steady-state kinetic analysis of Ape1 AP endonuclease activity at 10 mM Mg2+ with and without 5 mM ATP indicates a less than 2fold difference in KM-value but an 19fold enhancement in kcat in the presence of ATP, suggesting an enhancement of the catalytic reaction specifically
-
additional information
additional information
-
Km for AP cleavage is similar to that for 5'-deoxyribose-5-phosphate removal, it explains the relative difference in apurinic/apyrimidinic cleavage observed with the plasmid and apurinic/apyrimidinic duplex oligonucleotide with the former containing a 100fold higher concentration of apurinic/apyrimidinic sites (100 uracil residues per plasmid molecule) than the oligonucleotides-based substrate.
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000153
12-mer oligodeoxyribonucleotide containing a natural AP site
-
mutant Y171F/P173L/N174K, pH 7.5, 25C
-
2.8
12-mer oligodeoxyribonucleotide containing a natural AP site
-
wild-type, pH 7.5, 25C
-
1
12-mer oligodeoxyribonucleotide containing a tetrahydrofuran analogue at the natural AP site
-
wild-type, pH 7.5, 25C
-
0.58
18-mer containing P33-labeled tetrahydrofuran
-
enzyme phosphorylated by casein kinase II, pH 7.5, 22C
-
5.7
18-mer containing P33-labeled tetrahydrofuran
-
enzyme dephosphorylated by lambda phosphatase, pH 7.5, 22C
-
2.3
2-deoxyribonolactone
-
pH 7.6, room temperature
26500
34FDNA
-
-
-
438
34FRNA
-
-
-
0.03
35 base pair oligonucleotide containing 5,6-dihydrouracil opposite A
-
pH 7.6, 37C, wild-type enzyme
-
1.37
35 base pair oligonucleotide containing 5,6-dihydrouracil opposite A
-
pH 7.6, 37C, mutant enzyme R184A
-
0.043
35 base pair oligonucleotide containing 5,6-dihydrouracil opposite G
-
pH 7.6, 37C, wild-type enzyme
-
0.17
35 base pair oligonucleotide containing 5,6-dihydrouracil opposite G
-
pH 7.6, 37C, mutant enzyme R184A
-
0.098
35 base pair oligonucleotide containing 5,6-dihydroxy-5,6-dihydrothymine opposite A
-
pH 7.6, 37C, mutant enzyme R184A; pH 7.6, 37C, wild-type enzyme
-
0.075
35 base pair oligonucleotide containing 5,6-dihydroxy-5,6-dihydrothymine opposite G
-
pH 7.6, 37C, wild-type enzyme
-
1.6
35 base pair oligonucleotide containing 5,6-dihydroxy-5,6-dihydrothymine opposite G
-
pH 7.6, 37C, mutant enzyme R184A
-
0.0007
37mer with AP/A
-
pH 6.8, 37C, Ntg1p
-
0.00512
37mer with AP/A
-
pH 6.8, 37C, Ntg2p
-
0.015
37mer with AP/C
-
pH 6.8, 37C, Ntg2p
-
0.0225
37mer with AP/C
-
pH 6.8, 37C, Ntg1p
-
0.00108
37mer with AP/G
-
pH 6.8, 37C, Ntg1p
-
0.00323
37mer with AP/G
-
pH 6.8, 37C, Ntg2p
-
0.007
37mer with AP/T
-
pH 6.8, 37C, Ntg1p
-
0.0233
37mer with AP/T
-
pH 6.8, 37C, Ntg2p
-
0.00833
37mer with dihydrouridine
-
pH 6.8, 37C, Scr2
-
0.0717
37mer with dihydrouridine
-
pH 6.8, 37C, Scr1
-
2.91
43-mer oligonucleotide containing the AP-site analog THF at nt 31
-
mutant C99S, presence of 2 mM Mg2+
-
3.36
43-mer oligonucleotide containing the AP-site analog THF at nt 31
-
wild-type, presence of 2 mM Mg2+
-
0.0000048
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant deltaQLY, Nei placed opposite G
0.000013
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant Q261A, Nei placed opposite C
0.000015
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant Q261A, Nei placed opposite G
0.000023
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant Q261A, Nei placed opposite A
0.000065
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant QLY/AAA, Nei placed opposite G
0.000067
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant Q261A, Nei placed opposite T
0.00007167
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant QLY/AAA, Nei placed opposite A
0.000583
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
wild-type, Nei placed opposite A
0.003167
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
wild-type, Nei placed opposite T
0.008167
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
wild-type, Nei placed opposite C
0.01167
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant QLY/AAA, Nei placed opposite T
0.013
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
mutant QLY/AAA, Nei placed opposite C
0.07167
5'-CTCTCCCTTC-5,6-dihydrouracil-CTCCTTTCCTCT-3'
P50465
wild-type, Nei placed opposite G
0.00783
5'-CTCTCCCTTC-8-oxo-7,8-dihydroguanine-CTCCTTTCCTCT-3'
P50465
wild-type, Nei placed opposite A
0.01317
5'-CTCTCCCTTC-8-oxo-7,8-dihydroguanine-CTCCTTTCCTCT-3'
P50465
wild-type, Nei placed opposite G
0.01583
5'-CTCTCCCTTC-8-oxo-7,8-dihydroguanine-CTCCTTTCCTCT-3'
P50465
wild-type, Nei placed opposite C
0.023
5'-CTCTCCCTTC-8-oxo-7,8-dihydroguanine-CTCCTTTCCTCT-3'
P50465
wild-type, Nei placed opposite T
0.0272
5'-Cy3-CAAGGTAGTrUATCCTTG-1-Black Hole Quencher1-3'
-
recombinant enzyme
-
0.168
5'-Cy3-CAAGGTAGTrUATCCTTG-1-Black Hole Quencher1-3'
-
native enzyme
-
0.0025
5'-GACAAGCGCAG-(5R,6S)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
mutant deltaQLY, Nei placed opposite A
0.00583
5'-GACAAGCGCAG-(5R,6S)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
mutant Q261A, Nei placed opposite G
0.016
5'-GACAAGCGCAG-(5R,6S)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
mutant QLY/AAA, Nei placed opposite G
0.02167
5'-GACAAGCGCAG-(5R,6S)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
mutant QLY/AAA, Nei placed opposite T
0.03
5'-GACAAGCGCAG-(5R,6S)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
wild-type, Nei placed opposite G
0.035
5'-GACAAGCGCAG-(5R,6S)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
wild-type, Nei placed opposite A
0.04167
5'-GACAAGCGCAG-(5R,6S)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
wild-type, Nei placed opposite C
0.0483
5'-GACAAGCGCAG-(5R,6S)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
wild-type, Nei placed opposite T
0.00567
5'-GACAAGCGCAG-(5S,6R)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
mutant Q261A, Nei placed opposite G
0.0112
5'-GACAAGCGCAG-(5S,6R)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
wild-type, Nei placed opposite T
0.0115
5'-GACAAGCGCAG-(5S,6R)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
wild-type, Nei placed opposite C
0.023
5'-GACAAGCGCAG-(5S,6R)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
wild-type, Nei placed opposite A
0.0567
5'-GACAAGCGCAG-(5S,6R)-2'-deoxy-5,6-dihydroxyuridine-CAGCCGAACAC-3'
P50465
wild-type, Nei placed opposite G
3.2
5'-TCGAGGATCCTGAGCTCGAGTCGACGXTCGCGAATTCTGCGGATCCAAGC-3'
-
pH 7.5, 37C
-
4.2
5'-TCGAGGATCCTGAGCTCGAGTCGACGXTCGCGAATTCTGCGGATCCAAGC-3'
P28352
pH 7.5, 37C
-
0.00333
5,6-dihydrothymidine/A
-
pH 7.5, 37C
0.00417
5,6-dihydrothymidine/A
-
pH 7.5, 37C
0.00567
5-hydroxy-2'-deoxyuridine/G
-
pH 7.5, 37C
-
72
AP-DNA
-
mutant Y72A
-
90
AP-DNA
-
wild-type
-
354
AP-DNA
-
mutant Y72F
-
7680
AP-DNA
-
mutant R37A
-
174
AP-DNA-DNA
-
-
-
54
AP-DNA-RNA
-
-
-
2.4
apruinic/apyrimidinic site
-
pH 7.6, room temperature
-
10
apurinic/apyrimidinic site
-
5' cleavage of a reduced AP site
-
0.0015
apurinic/apyrimidinic sites
P50465
mutant QLY/AAA, Nei placed opposite A
-
0.00183
apurinic/apyrimidinic sites
P50465
mutant QLY/AAA, Nei placed opposite G
-
0.00883
apurinic/apyrimidinic sites
P50465
wild-type, Nei placed opposite G
-
0.01067
apurinic/apyrimidinic sites
P50465
wild-type, Nei placed opposite A
-
1140
DNA
-
LMAP mutant A138D, 3'-phosphodiesterase activity
2340
DNA
-
Ape1, 3'-phosphodiesterase activity
10440
DNA
-
LMAP, 3'-phosphodiesterase activity
16440
DNA
-
Ape mutant D70A, 3'-phosphodiesterase activity
0.000035
DNA containing 5-OH-C/A
-
+ G 212 mutant, pH 7.5, 37C, presence of Mg2+
-
0.0000667
DNA containing 5-OH-C/A
-
+ G 212 mutant, pH 7.5, 37C, presence of EDTA
-
0.0001
DNA containing 5-OH-C/A
-
P211R mutant, pH 7.5, 37C, presence of Mg2+
-
0.000333
DNA containing 5-OH-C/A
-
wild-type, pH 7.5, 37C, presence of Mg2+
-
0.0005
DNA containing 5-OH-C/A
-
P211R mutant, pH 7.5, 37C, presence of EDTA; wild-type, pH 7.5, 37C, presence of EDTA
-
0.000233
DNA containing 5-OH-C/G
-
+ G 212 mutant, pH 7.5, 37C, presence of Mg2+
-
0.0005
DNA containing 5-OH-C/G
-
P211R mutant, pH 7.5, 37C, presence of Mg2+
-
0.000583
DNA containing 5-OH-C/G
-
P211R mutant, pH 7.5, 37C, presence of EDTA
-
0.000667
DNA containing 5-OH-C/G
-
wild-type, pH 7.5, 37C, presence of EDTA
-
0.000833
DNA containing 5-OH-C/G
-
wild-type, pH 7.5, 37C, presence of Mg2+
-
0.00117
DNA containing 5-OH-C/G
-
+ G 212 mutant, pH 7.5, 37C, presence of EDTA
-
0.0007
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y171A, high salt concentration (150 mM NaCl)
0.0008
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y171A, low salt concentration (82 mM NaCl)
0.0009
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y171F, low salt concentration (82 mM NaCl)
0.2
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y128A, high salt concentration (150 mM NaCl)
0.3
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y269A, high salt concentration (150 mM NaCl)
0.5
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y128A, low salt concentration (82 mM NaCl)
1.3
DNA containing an abasic site
-
pH 7.5, mutant enzyme Y269A, low salt concentration (82 mM NaCl)
1.6
DNA containing an abasic site
-
pH 7.5, wild-type enzyme, high salt concentration (150 mM NaCl)
10
DNA containing an abasic site
-
pH 7.5, wild-type enzyme, low salt concentration (82 mM NaCl)
0.0000567
DNA containing dihydrouracil
-
K212R mutant, pH 8, 37C
-
0.002
DNA containing dihydrouracil
-
wild-type, pH 8, 37C
-
4.1
double-stranded DNA with abasic sites
-
-
-
0.0027
duplex oligonucleotide containing a 5,6-dihydro-2'-deoxyuridine*G pair
-
pH 6.8, 37C, necleotide incison repair activity
-
0.002
duplex oligonucleotide containing a alpha-2'-deoxyadenosine*T pair
-
pH 6.8, 37C,nucleotide incison repair activity
-
0.0003
oligomer with G/U pair
-
H309N mutant, pH 7.5
-
0.02
oligomer with G/U pair
-
D283/D308A mutant, pH 7.5
-
0.3
oligomer with G/U pair
-
D283A mutant, pH 7.5
-
1.2
oligomer with G/U pair
-
D308A mutant, pH 7.5
-
10
oligomer with G/U pair
-
wild-type, pH 7.5
-
4.2
single-stranded DNA with abasic sites
-
-
-
0.01
tetrahydrofuranyl/G
-
pH 7.5, 37C
-
0.0283
tetrahydrofuranyl/G
-
pH 7.5, 37C
-
1020
THF-containing oligonucleotide
-
APE1 mutant D70A, AP endonuclease activity
-
6300
THF-containing oligonucleotide
-
LMAP mutant A138D, AP endonuclease activity
-
12120
THF-containing oligonucleotide
-
APE1, AP endonuclease activity
-
19260
THF-containing oligonucleotide
-
LMAP, AP endonuclease activity
-
0.0117
[ubiquitin carrier protein UB2R2]-S-ubiquitinyl-L-cysteine
-
pH 7.5, 37C
-
0.0158
[ubiquitin carrier protein UB2R2]-S-ubiquitinyl-L-cysteine
-
pH 7.5, 37C
-
0.0267
5-hydroxy-2'-deoxyuridine/G
-
pH 7.5, 37C
-
additional information
AP-DNA
-
not detected in mutant E261Q
-
0.002
duplex oligonucleotide containing a tetrahydrofuran*G pair
-
pH 6.8, 37C, nucleotide incison repair activity
-
additional information
additional information
-
wild-type APE1 cleaves AP sites more efficiently than D70A mutant with a kcat value for the incision of an AP site aproximately 10fold higher
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.63
12-mer oligodeoxyribonucleotide containing a natural AP site
-
mutant Y171F/P173L/N174K, pH 7.5, 25C
0
30000
12-mer oligodeoxyribonucleotide containing a natural AP site
-
wild-type, pH 7.5, 25C
0
10000
12-mer oligodeoxyribonucleotide containing a tetrahydrofuran analogue at the natural AP site
-
wild-type, pH 7.5, 25C
0
7200
18-mer containing P33-labeled tetrahydrofuran
-
enzyme phosphorylated by casein kinase II, pH 7.5, 22C
0
12000
18-mer containing P33-labeled tetrahydrofuran
-
enzyme dephosphorylated by lambda phosphatase, pH 7.5, 22C
0
64.15
5'-Cy3-CAAGGTAGTrUATCCTTG-1-Black Hole Quencher1-3'
-
recombinant enzyme
0
2620
5'-Cy3-CAAGGTAGTrUATCCTTG-1-Black Hole Quencher1-3'
-
native enzyme
0
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.025
(p(2,3-dihydroxy-5-oxopentyl phosphate))
-
pH 7.6, 37C
-
0.0267
(pA)10
-
pH 7.6, 37C
0.0025
(pA)10*d(pT)10, (pA)11*d(pT)11
-
pH 7.6, 37C
-
0.03
(pA)12, (pA)16
-
pH 7.6, 37C
-
0.0025
(pA)16*d(pT)16
-
pH 7.6, 37C
-
0.263
(pA)2
-
pH 7.6, 37C
0.199
(pA)3
-
pH 7.6, 37C
0.183
(pA)4
-
pH 7.6, 37C
0.00759
(pA)4*d(pT)4
-
pH 7.6, 37C
-
0.1
(pA)6
-
pH 7.6, 37C
0.0214
(pA)6*d(pT)6
-
pH 7.6, 37C
-
0.0367
(pA)8
-
pH 7.6, 37C
0.0063
(pA)8*d(pT)8
-
pH 7.6, 37C
-
0.0269
(pA)9
-
pH 7.6, 37C
0.0447
(pC)10
-
pH 7.6, 37C
0.038
(pC)14
-
pH 7.6, 37C
-
0.316
(pC)2
-
pH 7.6, 37C
0.214
(pC)4
-
pH 7.6, 37C
0.12
(pC)6
-
pH 7.6, 37C
0.0708
(pC)8
-
pH 7.6, 37C
0.157
(pU)10
-
pH 7.6, 37C
0.01
(pU)10*(pA)10
-
pH 7.6, 37C
-
0.159
(pU)11
-
pH 7.6, 37C
-
0.158
(pU)16
-
pH 7.6, 37C
-
0.01
(pU)16*(pA)16
-
pH 7.6, 37C
-
0.7
(pU)4
-
pH 7.6, 37C
0.135
(pU)4*(pA)4
-
pH 7.6, 37C
-
0.339
(pU)6
-
pH 7.6, 37C
0.0166
(pU)6*(pA)6
-
pH 7.6, 37C
-
0.178
(pU)8
-
pH 7.6, 37C
0.158
(pU)9
-
pH 7.6, 37C
0.0167
(pU)9*(pA)9
-
pH 7.6, 37C
-
0.00018
1-methyl-4-[(1E)-1-[2-(6-methyl[1,3]dioxolo[4,5-g]quinolin-8-yl)hydrazinylidene]ethyl]-2-phenyl-1,2-dihydro-3H-pyrazol-3-one
-
pH not specified in the publication, temperature not specified in the publication
0.00019
8-[(2E)-2-(3-methoxybenzylidene)hydrazinyl]-6-methyl[1,3]dioxolo[4,5-g]quinoline
-
pH not specified in the publication, temperature not specified in the publication
0.00012
8-[(2E)-2-[(9-ethyl-9H-carbazol-3-yl)methylidene]hydrazinyl]-6-methyl[1,3]dioxolo[4,5-g]quinoline
-
pH not specified in the publication, temperature not specified in the publication
0.373
AMP
-
pH 7.6, 37C
0.447
CMP
-
pH 7.6, 37C
0.059
d(p((3-hydroxytetrahydrofuran-2-yl)methyl phosphate))
-
pH 7.6, 37C
0.00166
d(pA)10
-
pH 7.6, 37C
0.00033
d(pA)10*d(pT)10
-
pH 7.6, 37C
-
0.0017
d(pA)12
-
pH 7.6, 37C
0.00036
d(pA)12*d(pT)12
-
pH 7.6, 37C
-
0.0017
d(pA)14
-
pH 7.6, 37C
0.00033
d(pA)14*d(pT)14
-
pH 7.6, 37C
-
0.00166
d(pA)16
-
pH 7.6, 37C
0.00033
d(pA)16*d(pT)16
-
pH 7.6, 37C
-
0.05
d(pA)2
-
pH 7.6, 37C
0.0366
d(pA)2*d(pT)2
-
pH 7.6, 37C
-
0.00033
d(pA)20*(pT)20
-
pH 7.6, 37C
-
0.033
d(pA)4
-
pH 7.6, 37C
0.0266
d(pA)4*d(pT)4
-
pH 7.6, 37C
-
0.0172
d(pA)6
-
pH 7.6, 37C
0.0118
d(pA)6*d(pT)6
-
pH 7.6, 37C
-
0.0025
d(pA)8
-
pH 7.6, 37C
0.0093
d(pA)8*d(pT)8
-
pH 7.6, 37C
-
0.0033
d(pC)10
-
pH 7.6, 37C
0.0033
d(pC)11, d(pC)13
-
pH 7.6, 37C
-
0.14
d(pC)2
-
pH 7.6, 37C
0.06
d(pC)3
-
pH 7.6, 37C
0.0217
d(pC)5
-
pH 7.6, 37C
0.01
d(pC)7
-
pH 7.6, 37C
0.0047
d(pC)9
-
pH 7.6, 37C
0.102
d(pG)2
-
pH 7.6, 37C
0.0383
d(pG)4
-
pH 7.6, 37C
0.0144
d(pG)6
-
pH 7.6, 37C
0.0054
d(pG)8
-
pH 7.6, 37C
0.0025
d(pT)10
-
pH 7.6, 37C
0.0025
d(pT)11, d(pT)12, d(pT)14
-
pH 7.6, 37C
-
0.00257
d(pT)15
-
pH 7.6, 37C
-
0.1166
d(pT)2
-
pH 7.6, 37C
0.0667
d(pT)3
-
pH 7.6, 37C
0.045
d(pT)4
-
pH 7.6, 37C
0.0246
d(pT)6
-
pH 7.6, 37C
0.0083
d(pT)8
-
pH 7.6, 37C
0.165
dAMP
-
pH 7.6, 37C
0.1633
dCMP
-
pH 7.6, 37C
0.1666
dGMP
-
pH 7.6, 37C
0.1633
dTMP
-
pH 7.6, 37C
0.0117
d[(p((3-hydroxytetrahydrofuran-2-yl)methyl phosphate))3pT]
-
pH 7.6, 37C
0.0052
d[(p((3-hydroxytetrahydrofuran-2-yl)methyl phosphate))5pT]
-
pH 7.6, 37C
0.0023
d[(p((3-hydroxytetrahydrofuran-2-yl)methyl phosphate))7pT]
-
pH 7.6, 37C
0.001
d[(p((3-hydroxytetrahydrofuran-2-yl)methyl phosphate))9pT]
-
pH 7.6, 37C
50
NaCl
-
-
0.36
NaH2PO4
-
pH 7.6, 37C
1.873
UMP
-
pH 7.6, 37C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.016
2,2'-(2-oxo-1H-benzimidazole-1,3(2H)-diyl)diacetic acid
-
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.011
2,2'-(3,7-dioxo-5,7-dihydro-1H,3H-benzo[1,2-c:4,5-c']difuran-1,5-diyl)diacetic acid
-
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50 mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.008
2,2'-[(6-oxo-6H-benzo[c]chromene-1,3-diyl)bis(oxy)]dipropanoic acid
-
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.019
2,2'-[(6-phenylpyrimidine-2,4-diyl)disulfanediyl]diacetic acid
-
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.004
2,2'-[butane-1,4-diylbis(1H-benzimidazole-2,1-diyl)]diacetic acid
-
small-molecule inhibitor containing 4 H-bond acceptors and 3 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.0021
2,4,9-trimethylpyridino[2,3-b]quinoline-5-ylamine
-
-
0.009
2-((Z)-2-oxo-3-(4-oxo-2-thioxothiazolidin-5-ylidene)indolin-1-yl)acetic acid
-
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.008
2-(5-((2-(2-carboxyphenyl)-1,3-dioxo)-2,3-dihydro-1H-isoindol-5-yl)carbonyl-1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)benzoic acid
-
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
-
0.003
2-[(5Z)-5-[1-(carboxymethyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid
-
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.017
3,3'-(1,3,4-thiadiazole-2,5-diyldisulfanediyl)dipropanoic acid
-
small-molecule inhibitor containing 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.015
3,3'-(2-thioxo-1H-benzimidazole-1,3(2H)-diyl)dipropanoic acid
-
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.011
3-((3,4-dimethylphenoxy)methyl)furan-2-carboxylic acid
-
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.027
3-((pyridin-2-ylthio)methyl)benzofuran-2-carboxylic acid
-
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.004
3-(1-(carboxymethyl)-5-(4-chlorophenyl)-1H-pyrrol-2-yl)propanoic acid
-
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.009
3-(1-(carboxymethyl)-5-(4-fluorophenyl)-1H-pyrrol-2-yl)propanoic acid
-
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.009
3-(1-(carboxymethyl)-5-(thiophen-2-yl)-1H-pyrrol-2-yl)propanoic acid
-
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.012
3-(1-(carboxymethyl)-5-p-tolyl-1H-pyrrol-2-yl)propanoic acid
-
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.02
3-(2-carboxyethyl)-4-hydroxyquinoline-6-carboxylic acid
-
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.006
3-(5-((E)-(3-(carboxymethyl)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl)furan-2-yl)benzoic acid
-
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.006
3-[(4Z)-4-[1-(carboxymethyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-5-oxo-2-thioxoimidazolidin-1-yl]propanoic acid
-
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.02
3-[(6-amino-9H-purin-8-yl)sulfanyl]propanoic acid
-
small-molecule inhibitor containing 3 H-bond acceptors and 1 negative ionizable feature, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.015
3-[[4-(carboxymethyl)benzyl]sulfanyl]-8-methyl-5H-[1,2,4]triazino[5,6-b]indole-5-carboxylic acid
-
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.0064
4-((2,6,8-trimethylquinolin-4-yl)amino)phenol
-
-
0.006
4-((2-carboxyphenoxy)methyl)-2,5-dimethylfuran-3-carboxylic acid
-
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.01
4-(4-(4-carboxyphenoxy)phenylsulfonyl)benzene-1,2-dioic acid
-
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.006
4-(4-(4-carboxyphenylsulfonyl)phenyl)sulfanylbenzene-1,2-dioic acid
-
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. Then, 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.004
4-(4-(4-carboxyphenylthio)phenylsulfonyl)benzene-1,2-dioic acid
-
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.02
4-([[(3-carboxy-5-methylfuran-2-yl)methyl]sulfanyl]methyl)-5-methylfuran-2-carboxylic acid
-
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.012
4-[(4Z)-4-[1-(carboxymethyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-5-oxo-2-thioxoimidazolidin-1-yl]butanoic acid
-
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.022
4-[[(2-carboxypropyl)sulfanyl]methyl]-5-methylfuran-2-carboxylic acid
-
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.005
5,5'-[methanediylbis(sulfanediylmethanediyl)]bis(2-methylfuran-3-carboxylic acid)
-
small-molecule inhibitor containing 4 H-bond acceptors and 3 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.016
5-(((tetrahydrofuran-2-yl)methylthio)methyl)-2-methylfuran-3-carboxylic acid
-
preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.006
5-([[(4-carboxy-5-methylfuran-2-yl)methyl]sulfanyl]methyl)-3-methylfuran-2-carboxylic acid
-
small-molecule inhibitor containing 4 H-bond acceptors and 3 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.0005
6-hydroxy-DL-DOPA
-
IC50 less than 0.0005 mM
0.05
ceftriaxone sodium
-
IC50 above 0.05 mM
0.05
cephapirin sodium
-
IC50 above 0.05 mM
0.0005
myricetin
-
IC50 less than 0.0005 mM
0.0016
N-(3-chlorophenyl)-5,6-dihydro-4H-cyclopenta[d]isoxazole-3-carboxamide
-
-
0.0005
Reactive blue 2
-
IC50 less than 0.0005 mM
0.011
[(3Z)-3-(3-[[(2-hydroxyphenyl)carbonyl]amino]-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)-2-oxo-2,3-dihydro-1H-indol-1-yl]acetic acid
-
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.006
[(3Z)-3-[3-(4-bromophenyl)-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene]-2-oxo-2,3-dihydro-1H-indol-1-yl]acetic acid
-
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.013
[(5Z)-5-[1-(carboxymethyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
-
small-molecule inhibitor containing 1 hydrophobic feature, 1 H-bond acceptor and 2 negative ionizable features, preincubation at a final concentration of 0.05 nM with the inhibitor in buffer (50mM NaCl, 1 mM HEPES, pH 7.5, 50 microM EDTA, 50 microM DTT, 10% glycerol, 7.5 mM MnCl2, 0.1 mg/ml bovine serum albumin, 10 mM 2-mercaptoethanol, 10% DMSO and 25 mM MOPS, pH 7.2) at 30C for 10 min. 200 nM of the 5'-end 32P-labeled linear oligonucleotide substrate is added
0.0017
[4-(2,5-dimethyl-1H-pyrrol-1-yl)phenoxy]acetic acid
-
-
0.0005
mitoxanthrone
-
IC50 less than 0.0005 mM
additional information
additional information
-
The APE1 inhibitory profile of some of the most potent compounds indicates that along with two terminal fingerprint negatively ionizable features or bioisostere groups of negatively ionizable features, an optimum sized central hydrophobic core with or without a favorably substituted H-bond acceptor-donor functional group is essential for a compound being recognized by APE1 and inhibit its catalytic activity
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
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
0.003133
-
-
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
-
-
additional information
-
-
additional information
-
specific activity in the picomolar range
additional information
-
-
additional information
P27695
The necessity of APE1 for cellular survival and its frequent overexpression in tumor cells strongly suggest a fundamental role of this protein in preventing cell death and in controlling cellular proliferation.; The regulatory functions of the different APE1 activities can be fine-tuned and implemented via three different mechanisms: increase in APE1 level after transcriptional activation, relocalization of APE1 from the cytoplasm to the nucleus, and modulation of the posttranslational modifications of APE1, such as acetylation and phosphorylation.
additional information
-
APE/Ref-1 accounts for 95% of the total apurinic/apyrimidinic endonuclease activity and is essential for the protection of cells against the toxic effects of several classes of DNA-damaging agents; APE/Ref-1 is involved in the regulation of metastatic potential in melanoma cells; APE/Ref-1 is very sensitive to redox-status alterations. ROS regulates its activity and expression on both transcriptional and posttranscriptional levels; Increased expression of APE/Ref-1 protein in nucleus of different human melanoma cell lines; involvement of APE/Ref-1 in the process of inflammation; oxidized APE/Ref-1 lacks endonuclease activity
additional information
-
750 nM substrate and 100 nM enzyme and a reaction time of 3 h is sufficient to convert most, if not all, of the Rp stereoisomer substrate DNA into product; the enzyme is responsible for eliminating as many as 105 potentially mutagenic and genotoxic lesions from the genome of each cell every day
additional information
-
APE1 exonuclease activity; APE1 is most efficiently (5% yield) modified by DNA substrate bearing the 5'-pF group (DNAFAP-pF), which flanks a nick. This DNA structure is a model of a short-patch BER intermediate or a long-patch BER product and is an analog of the product of endonuclease or substrate of the exonuclease APE1 activity
additional information
-
overexpression of Ape1 reduces cisplatin-induced apoptosis in sensory neuronal cell cultures
additional information
-
By adding of purified Y-box-binding protein-1 to the nuclease reaction containing 0.2 microg of TAP-hNTH1 (minimum of protein required to see cleavage of the DNA duplex), there is an 12fold increase in cleavage activity; no activity is detected using a probe without 8-oxoguanine residue demonstrating the specificity of hNTH1 for oxidized DNA duplex; TAP-hNTH1 expressing cells transfected with a small interference RNA specific to hNTH1 show decreased protein levels and nuclease activities toward the radioactive duplex 8-oxoguanine; the MCF7-eluted TAP-hNTH1 protein exhibits nuclease activities on a radioactive duplex containing 8-oxoguanine residues; Y-box-binding protein-1 binds specifically to the auto-inhibitory domain of hNTH1 to stimulating its activity; Y-box-binding protein-1 strongly stimulates in vitro the activity of hNTH1 toward DNA duplex probes containing oxidized bases, lesions prone to be present in cisplatin treated cells
additional information
-
genomic instability increased in the livers of 1-month-old methionine adenosyltransferase 1a knock-out mice, compared with wild-type mice, whereas Apex1 mRNA and protein levels are reduced by 20% and 50%, in knock-out mice of all ages; in mouse cultured hepatocytes, APEX1 protein levels decrease by 40% despite the increase in mRNA levels, and treatment with 2 mmol/L S-adenosylmethionine is able to completely prevent it
additional information
-
APE-1 expression in tissues from Helicobacter pylori-infected subjects is significantly increased compared to that in tissues from subjects after successful eradication therapy
additional information
-
cells lacking Nfo and ExoA are around 1.2times more susceptible to H2O2 treatment than cells of the parental strain; compared to wild-type spores, nfo and exoA spores exhibit slower outgrowth, although they exhibit essentially identical rates of germination when germination is judged by determining the decrease in the OD600 of spore cultures shortly after addition of spores to germination medium; germination rate of spores lacking both Nfo and ExoA is similar to that of wild-type spores, but the return to vegetative growth (outgrowth) is significantly slower for the nfo exoA spores; The absence of Nfo and ExoA in uvrA and recA spores resulted in a slow-outgrowth phenotype; the mutation frequency in outgrown nfo exoA spores is 10fold higher than that in outgrown wild-type spores treated with H2O2; the outgrowth of spores lacking the enzyme is slowed, and the spores have an elevated mutation frequency, suggesting that these enzymes repair DNA lesions induced by oxidative stress during spore germination and outgrowth.
additional information
-
decreased levels of AP endonuclease activity (smaller amount of cleaved 14-mer products and greater amount of uncleaved 26-mer oligonucleotides) are observed in both H460 and H69 cells that express high levels of endogenous Bcl2 as compared with the other cell lines that express undetectable levels of Bcl2; expression of endogenous Bcl2 is associated with decreased APE1 endonuclease activity in various human lung cancer cells
additional information
-
Ape1 has only slightly more robust activity on the partial DNA-DNA duplex than on the comparable DNA/RNA duplex.; creation of three-strand substrates provided a 2- to 2.5fold increase in the specific activity of Ape1 over the partial duplex with the abasic lesion positioned at the ssDNA-dsDNA junction (54Fendbubble18-18DNA); substrates with either a purine (G) or a pyrimidine (C) positioned opposite the AP site and two purines flanking the abasic site shows that Ape1 incision activity under optimal reaction conditions is two to threefold higher with the GFT-CCA, CFA-GCT, and CFT-GGA arrangements relative to GFA-CCT
additional information
-
10 mM Mg2+, all Cys mutants except those with C99S mutation are at least as active as the wild-type APE1; activity of Cys99 mutants is comparable to that of the wild-type in 0.5 or 2mM Mg2+, while only the Cys99 mutants are strongly inhibited at 5 mM and higher Mg2+ concentration; Cys99 in hAPE1 as a critical residue modulating function for ensuring optimum activity
additional information
-
Ape1/Ref-1 increases the expression of glial cell-derived neurotropic factor receptor alpha1 (GFRalpha1), a key receptor for glial cell-derived neurotropic factor (GDNF). Expression of Ape1/Ref- 1 leads to an increase in the GDNF responsiveness in human fibroblast. Ape1/Ref-1 induced GFRalpha1 transcription through enhances binding of NF-kappaB complexes to the GFRalpha1 promoter.; GFRalpha1 levels correlates proportionally with Ape1/Ref-1 in cancer cells; in neuronal cells, the Ape1/Ref-1-mediated increase in GDNF responsiveness not only stimulated neurite outgrowth but also protected the cells from beta-amyloid peptide and oxidative stress; the knockdown of endogenous Ape1/Ref-1 in pancreatic cancer cells markedly suppresses GFRalpha1 expression and invasion in response to GNDF, while overexpression of GFRalpha1 restores invasion
additional information
-
the redox activity of APE/Ref-1 is regulated by chemical reduction and oxidation in vitro
additional information
-
T58C zApe has near wild-type human Ape1 redox activity in the transactivation assay
additional information
-
Cell-based analysis of redox activity for hApe1 Cys-mutants using an in vitro EMSA redox assay in which reduction of the trancription factor AP-1 by hApe1 results in a shifted band. Only C65A hApe1 is found to be redox inactive.
additional information
-
Activity is determined with phage T4 AP DNA endonuclease assay agrees with divalent metal (Mn2+ and Zn2+) content measured for purified His-tagged Endo IV wild-type and mutant proteins, except for E261Q and to a lesser extent E145Q, which are adjacent in the active site. Mutations of the first-shell metal-ion binding residues resulted in mild (10fold reduction activity, H109N and D179N), severe (100-2600fold reduction in activity, H69N, H182N, D229N, H216N and H231N) or complete loss (E145Q, E261Q) of catalytic activity in both the T4 AP-DNA endonuclease assay and the AP-oligonucleotide cleavage assay
additional information
-
Mutation D70A has decreased AP incision activity; The nucleotide incision repair (NIR) activity of APE1 provides an alternative and complementary repair pathway to BER; The specific activity is significantly increased in the case of the D70A mutant enzyme. Upon incubation at 37C, 5 nM of purified APE1 mutant D70A remove most of the 3'-phosphoglycolate residues in 10 min, while the same enzyme amounts of APE1 converts only around 60% and 50% of the substrate into the corresponding 3'-OH form.
additional information
-
Mutation A138D has decreased AP incision activity; upon incubation at 37C, 5 nM of LMAP protein remove most of the 3'-PG residues in 10 min, while the LMAP mutant A138D converts only around 50% of the substrate into the corresponding 3'-OH form
additional information
-
mRNA levels of APE/Ref-1 decrease 43.36% and increase 31.75% in acute spinal cord injury and spinal cord injury plus embryonic neural stem cells therapy groups, respectively in acute study groups and decrease 31.97% and increase 65.13% in chronic spinal cord injury and spinal cord injury plus embryonic neural stem cells therapy groups in chronic study groups, when compared to the sham. After embryonic neural stem cells therapy, in both acute and chronic spinal cord injury groups APE/Ref-1 levels significantly improve.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.4 - 6.8
-
nucleotide incision repair activity
6.5 - 7.5
-
enzyme form B
6.5 - 9
-
enzyme form A
7
-
activity against OsO4-treated DNA
7
-
exonuclease assay, buffer B
7
-
assay at
7.2
-
assay at
7.4
P22936
activity assay, oligonucleotide cleavage assay, endonuclease and 3'-phosphodiesterase activity is measured
7.4
-
AP endonuclease assay
7.5 - 8
Q8U437
in Tris-HCl buffer
7.5 - 8
-
-
7.5 - 8
P28352
-
7.5 - 8.7
-
-
7.5 - 9
-
-
7.5
-
assay at
7.5
-
sharp optimum, activity against apurinic and apyrimidinic sites
7.5
-
endonuclease D4
7.5
-
activity assay
7.5
-
nuclease assay
7.5
-
incision assay using synthetic oligonucleotides
7.5
-
3'-exonuclease activity assay
7.5
O15922
activity assay
7.5
-
AP endonuclease activity assay
7.5
-
AP-endonuclease assay
7.5
-
AP-endonuclease assay; DNA-binding assay
7.5
-
assay at
7.8 - 8.2
-
AP endonuclease activity
8
-
isozyme 0.3 M
8
-
endonuclease E
8
-
exonuclease assay, buffer A
8
-
DNA cleavage reaction; protein-DNA binding assay
8
-
virion associated APE catalytic activity assay
8
-
activity assay
8
-
AP endonuclease assay and 3'-5' exonuclease assay
8
-
electrophoretic mobility shift assay
8
-
assay at (AP endonuclease activity)
8
-
assay at (endonuclease activity)
8.1
-
assay at
8.5
-
endonuclease D1, D2, D3
8.5
-
assay at
9.2
-
AP-endonuclease assay
9.2
-
calculated from sequence
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5 - 9
-
about 40% of activity maximum at pH 5.5 and pH 9.0
6 - 8.5
-
endonuclease activity
6.2 - 8.1
-
pH 6.2 and pH 8.1: 50% of activity maximum, activity against OsO4-treated DNA
6.5 - 10.5
-
pH 6.5: about 25% of activity maximum, pH 10.5: about 20% of activity maximum
7 - 8
O15922
-
7 - 9
-
pH 7 and pH 9: 50% of maximum activity
7.2 - 7.8
-
pH 7.2 and pH 7.8: 50% of activity maximal, activity against apyrimidinic and apurinic sites
7.3 - 9.5
-
pH 7.3: about 50% of maximal activity, pH 9.5: about 45% of maximal ativity, glycosylase/lyase activity is very similar to that of the glycosylase activity alone
7.4 - 8.6
-
about 80% of activity maximum at pH 7.4 and pH 8.2, 62% of maximum activity at pH 8.6
7.5 - 10
O29876
pH 7.5: about 50% of maximal activity, pH 10.0: about 50% of maximal activity
7.5 - 8.3
-
pH 7.5: 50% of maximal activity, pH 8.3: activity maximum
8 - 9
-
50% of activity maximum, endonuclease D1, D2 and D3
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
-
assay at
23
-
electrophoretic mobility shift assay
25
-
nuclease assay
30
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
exonuclease assay
37
-
activity assay
37
-
incision assay using synthetic oligonucleotides
37
-
3'-exonuclease activity assay
37
O15922
activity assay
37
P22936
activity assay, oligonucleotide cleavage assay, endonuclease and 3'-phosphodiesterase activity is measured
37
-
AP endonuclease assay and 3'-5' exonuclease assay
37
-
AP endonuclease activity assay
37
-
AP-endonuclease assay
37
-
AP endonuclease assay
37
-
assay at
37
-
assay at
37
-
assay at
50
O29876
assay at
60
O29876
since the Tm-value of the DNA substrates (39-mer) is 74C, the activity above 60C is not convincible. The actual optimum temperature of the enzyme might be higher than 60C
65
-
DNA-binding assay
72
-
AP-endonuclease assay
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10
-
10C: about 15% of activity maximum, 60C: about 35% of activity maximum
35
-
35C: about 35% of activity maximum, 65C: about 25% of activity maximum
37 - 50
-
the enzyme is 6fold more active at 50C than at 37C, glycosylase/lyase activity is very similarto that of the glycosylase activity alone
40 - 80
O29876
40C: about 60% of maximal activity, 80C: about 70% of maximal activity
40
-
ExoIII rapidly loses activity with preheating at more than 40C, and almost completely lose it at 55C
40
-
TvoExo gradually loses AP endonuclease activity at more than 40C, but it retaines about 20% of activity at 80C
45
-
LplExo does not cleave AP-DNA after preheating at more than 45C
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
-
pH range 6-9
7.5
-
calculated
8
O35980
calculated from DNA sequence
9.9
-
calculated from DNA sequence
10
O35980
calculated from DNA sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
gastric adenocarcinoma cell-line
Manually annotated by BRENDA team
-
enzyme is present and active in the two replicative parasite forms, epimastigotes and amastigotes, as well as in the nonreplicative, infective trypomastigotes
Manually annotated by BRENDA team
-
enzyme is present and active in the two replicative parasite forms, epimastigotes and amastigotes, as well as in the nonreplicative, infective trypomastigotes
-
Manually annotated by BRENDA team
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primary cell line, murine B-cells are isolated from spleen by a negative depletion
Manually annotated by BRENDA team
P27695
APE1 is highly expressed in selected regions of the central nervous system
Manually annotated by BRENDA team
P27695
increased nuclear expression of APE1 in neuronal and glial cells in both familial and sporadic Alzheimer
Manually annotated by BRENDA team
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purified recombinant APE1 protein
Manually annotated by BRENDA team
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NRP and GRP-neuronal and glial restricted precursors are isolated from embryonic day 13.5 rats and transplantated into rats.
Manually annotated by BRENDA team
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human umbilical vein endothelial cells are infected with adenovirus encoding APE/Ref-1
Manually annotated by BRENDA team
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enzyme is present and active in the two replicative parasite forms, epimastigotes and amastigotes, as well as in the nonreplicative, infective trypomastigotes
Manually annotated by BRENDA team
-
enzyme is present and active in the two replicative parasite forms, epimastigotes and amastigotes, as well as in the nonreplicative, infective trypomastigotes
-
Manually annotated by BRENDA team
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APE-1 expression is mainly localized in epithelial cells within gastric adenoma
Manually annotated by BRENDA team
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SV40-transformed human skin fibroblasts, CS1AN.S3.G2
Manually annotated by BRENDA team
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human gastric epithelial cell line AGS
Manually annotated by BRENDA team
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from 2- to 3-month-old male C57/B6 mice isolated by collagenase perfusion
Manually annotated by BRENDA team
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hippocampal neuron
Manually annotated by BRENDA team
P27695
a reduction in APE1 expression, followed by an increase in the apoptotic rate, occurs in the hippocampus after a hypoxic-ischemic injury, patients with Alzheimer show an increased expression of APE1 levels in senile plaques and plaque-like structures
Manually annotated by BRENDA team
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1-month-old, from male methionine adenosyltransferase 1a knock-out and wild-type mice
Manually annotated by BRENDA team
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various cell lines, Bcl2, a major antiapoptotic and/or oncogenic protein, is found to co-express with APE1 in H69 and H460 but not in other tested lung cancer cells
Manually annotated by BRENDA team
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human peripheral macrophages
Manually annotated by BRENDA team
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mammary adenocarcinoma cell line
Manually annotated by BRENDA team
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embryonic fibroblast cell
Manually annotated by BRENDA team
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wm3211, wm1205, c83-2c, c81-46A, A375, c81-61
Manually annotated by BRENDA team
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APE-1 expression in gastric cancer tissues
Manually annotated by BRENDA team
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Helicobacter pylori (CagA+) water-extract protein (HPWEP)-stimulated
Manually annotated by BRENDA team
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APE1 protein is elevated in 72% of the tissues and among those with a known clinical outcome. There is a significant correlation between high APE1 expression levels and reduced survival times
Manually annotated by BRENDA team
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human prostate cancer cell line
Manually annotated by BRENDA team
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nuclear expression of APE1 in epidermal layers is markedly up-regulated in psoriatic skin, APE1 is essential for the transcriptional activation and nuclear translocation of hypoxia-inducible factor-1alpha and NF-kappaB
Manually annotated by BRENDA team
P27695
reduction in APE1 expression after ischemia
Manually annotated by BRENDA team
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only little activity in spores
Manually annotated by BRENDA team
Bacillus subtilis PS832
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-
-
Manually annotated by BRENDA team
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human acute monocytic leukemia cell line
Manually annotated by BRENDA team
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enzyme is present and active in the two replicative parasite forms, epimastigotes and amastigotes, as well as in the nonreplicative, infective trypomastigotes
Manually annotated by BRENDA team
-
enzyme is present and active in the two replicative parasite forms, epimastigotes and amastigotes, as well as in the nonreplicative, infective trypomastigotes
-
Manually annotated by BRENDA team
-
prepared from peripheral blood mononuclear cells
Manually annotated by BRENDA team
additional information
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Vero cell
Manually annotated by BRENDA team
additional information
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ganglioneuroma cell, dorsal root ganglions are collected from the spinal column, incubated with collagenase and mechanically dissociated
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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translocation of the cytoplasmic enzyme into the nucleus occurs during DNA damage
Manually annotated by BRENDA team
P27695
cytoplasmic localization of APE1in fibroblasts, spermatocytes, thyrocytes, lymphocytes, hepatocytes, and hippocampal cells is associated with high metabolic or proliferative rates and may be related to a cell cycle-dependent expression
Manually annotated by BRENDA team
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weak and diffuse cytosolic distribution under basal conditions
Manually annotated by BRENDA team
Saccharomyces cerevisiae D273-10B/A1
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-
-
Manually annotated by BRENDA team
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mtAPE, N-terminal truncation product of APE1
Manually annotated by BRENDA team
P27695
APE1 protein is also localized within mitochondria in different cell types, mitochondrial localization of APE1 is associated to a potential role in DNA repair of oxidized bases in the mitochondrial genome
Manually annotated by BRENDA team