Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

DNA-(apurinic or apyrimidinic site) lyase



Rattus norvegicus (Rat)
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli


Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 in DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA.1 Publication


The specific activity of the cleaved mitochondrial endodeoxyribonuclease appeared to be about 3-fold higher than of the full-length form. Extract of mitochondria, but not of nuclei or cytosol, cleaves recombinant APEX1 to generate a mitochondrial APEX1-sized product (By similarity).By similarity

Catalytic activityi

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.PROSITE-ProRule annotation


Mg2+By similarity, Mn2+By similarityNote: Probably binds two magnesium or manganese ions per subunit.By similarity

Enzyme regulationi

NPM1 stimulates endodeoxyribonuclease activity on double-stranded DNA with AP sites, but inhibits endoribonuclease activity on single-stranded RNA containing AP sites.By similarity


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi69Magnesium 1By similarity1
Metal bindingi95Magnesium 1By similarity1
Active sitei170By similarity1
Active sitei209Proton donor/acceptorBy similarity1
Metal bindingi209Magnesium 2By similarity1
Metal bindingi211Magnesium 2By similarity1
Sitei211Transition state stabilizerBy similarity1
Sitei282Important for catalytic activityBy similarity1
Metal bindingi307Magnesium 1By similarity1

GO - Molecular functioni

GO - Biological processi

  • aging Source: RGD
  • base-excision repair Source: RGD
  • cell redox homeostasis Source: RGD
  • cellular response to cAMP Source: RGD
  • cellular response to hydrogen peroxide Source: RGD
  • cellular response to organonitrogen compound Source: RGD
  • cellular response to peptide hormone stimulus Source: RGD
  • DNA demethylation Source: UniProtKB
  • DNA recombination Source: UniProtKB-KW
  • DNA repair Source: UniProtKB
  • negative regulation of smooth muscle cell migration Source: RGD
  • positive regulation of G1/S transition of mitotic cell cycle Source: RGD
  • regulation of apoptotic process Source: UniProtKB
  • regulation of mRNA stability Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • response to drug Source: RGD
  • response to organonitrogen compound Source: RGD
  • telomere maintenance Source: RGD
  • telomere maintenance via base-excision repair Source: RGD
  • transcription, DNA-templated Source: UniProtKB-KW


Molecular functionActivator, DNA-binding, Endonuclease, Exonuclease, Hydrolase, Lyase, Nuclease, Repressor, RNA-binding
Biological processDNA damage, DNA recombination, DNA repair, Transcription, Transcription regulation
LigandMagnesium, Metal-binding

Enzyme and pathway databases

ReactomeiR-RNO-110357. Displacement of DNA glycosylase by APEX1.
R-RNO-110362. POLB-Dependent Long Patch Base Excision Repair.
R-RNO-110373. Resolution of AP sites via the multiple-nucleotide patch replacement pathway.
R-RNO-5651801. PCNA-Dependent Long Patch Base Excision Repair.
R-RNO-73930. Abasic sugar-phosphate removal via the single-nucleotide replacement pathway.
R-RNO-73933. Resolution of Abasic Sites (AP sites).

Names & Taxonomyi

Protein namesi
Recommended name:
DNA-(apurinic or apyrimidinic site) lyase (EC:3.1.-.-, EC:
Alternative name(s):
APEX nuclease
Short name:
Apurinic-apyrimidinic endonuclease 1
Short name:
AP endonuclease 1
Redox factor-1
Cleaved into the following chain:
Gene namesi
Synonyms:Ape, Apex, Ref1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
  • UP000002494 Componenti: Chromosome 15

Organism-specific databases

RGDi2126. Apex1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002000121 – 317DNA-(apurinic or apyrimidinic site) lyaseAdd BLAST317
ChainiPRO_000040257431 – 317DNA-(apurinic or apyrimidinic site) lyase, mitochondrialBy similarityAdd BLAST287

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei6N6-acetyllysine; by EP300By similarity1
Modified residuei18PhosphoserineCombined sources1
Modified residuei26N6-acetyllysineBy similarity1
Modified residuei30N6-acetyllysineBy similarity1
Modified residuei31N6-acetyllysineBy similarity1
Modified residuei34N6-acetyllysineBy similarity1
Modified residuei53PhosphoserineBy similarity1
Disulfide bondi64 ↔ 92AlternateBy similarity
Modified residuei64S-nitrosocysteine; alternateBy similarity1
Modified residuei92S-nitrosocysteine; alternateBy similarity1
Modified residuei196N6-acetyllysineBy similarity1
Modified residuei232Phosphothreonine; by CDK5By similarity1
Modified residuei309S-nitrosocysteineBy similarity1

Post-translational modificationi

Phosphorylated. Phosphorylation by kinase PKC or casein kinase CK2 results in enhanced redox activity that stimulates binding of the FOS/JUN AP-1 complex to its cognate binding site. AP-endodeoxyribonuclease activity is not affected by CK2-mediated phosphorylation. Phosphorylation of Thr-232 by CDK5 in response to MPP+/MPTP (1-methyl-4-phenylpyridinium) reduces AP-endodeoxyribonuclease activity resulting in accumulation of DNA damage and contributing to neuronal death (By similarity).By similarity
Acetylated on Lys-6. Acetylation is increased by the transcriptional coactivator EP300 acetyltransferase, genotoxic agents like H2O2 and methyl methanesulfonate (MMS). Acetylation increases its binding affinity to the negative calcium response element (nCaRE) DNA promoter. The acetylated form induces a stronger binding of YBX1 to the Y-box sequence in the MDR1 promoter than the unacetylated form. Deacetylated on lysines. Lys-6 is deacetylated by SIRT1 (By similarity).By similarity
Cleaved at Lys-30 by granzyme A to create the mitochondrial form; leading in reduction of binding to DNA, AP endodeoxyribonuclease activity, redox activation of transcription factors and to enhanced cell death. Cleaved by granzyme K; leading to intracellular ROS accumulation and enhanced cell death after oxidative stress (By similarity).By similarity
Cys-64 and Cys-92 are nitrosylated in response to nitric oxide (NO) and lead to the exposure of the nuclear export signal (NES).By similarity
Ubiquitinated by MDM2; leading to translocation to the cytoplasm and proteasomal degradation.By similarity


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei30 – 31Cleavage; by granzyme ABy similarity2

Keywords - PTMi

Acetylation, Cleavage on pair of basic residues, Disulfide bond, Phosphoprotein, S-nitrosylation, Ubl conjugation

Proteomic databases


PTM databases



Gene expression databases

GenevisibleiP43138. RN.


Subunit structurei

Monomer. Homodimer; disulfide-linked. Component of the SET complex, composed of at least APEX1, SET, ANP32A, HMGB2, NME1 and TREX1. Associates with the dimer XRCC5/XRCC6 in a DNA-dependent manner. Interacts with SIRT1; the interaction is increased in the context of genotoxic stress. Interacts with HDAC1, HDAC2 and HDAC3; the interactions are not dependent on the APEX1 acetylation status. Interacts with XRCC1; the interaction is induced by SIRT1 and increased with the APEX1 acetylated form. Interacts with NPM1 (via N-terminal domain); the interaction is RNA-dependent and decreases in hydrogen peroxide-damaged cells. Interacts (via N-terminus) with YBX1 (via C-terminus); the interaction is increased in presence of APEX1 acetylated. Interacts with HNRNPL; the interaction is DNA-dependent. Interacts (via N-terminus) with KPNA1 and KPNA2. Interacts with TXN; the interaction stimulates the FOS/JUN AP-1 complex DNA-binding activity in a redox-dependent manner. Interacts with GZMA, KRT8, MDM2, POLB, PRDX6, PRPF19, RPLP0, TOMM20 and WDR77. Binds to CDK5 (By similarity).By similarity


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei308Interaction with DNA substrateBy similarity1

GO - Molecular functioni

  • NF-kappaB binding Source: RGD
  • protein complex binding Source: RGD

Protein-protein interaction databases



3D structure databases


Family & Domainsi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 32Necessary for interaction with YBX1, binding to RNA, association together with NPM1 to rRNA, endoribonuclease activity on abasic RNA and localization in the nucleoliBy similarityAdd BLAST32
Regioni22 – 32Necessary for interaction with NPM1 and for efficient rRNA bindingBy similarityAdd BLAST11
Regioni288 – 317Mitochondrial targeting sequence (MTS)By similarityAdd BLAST30


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi8 – 12Nuclear localization signal (NLS)By similarity5
Motifi63 – 79Nuclear export signal (NES)By similarityAdd BLAST17


The N-terminus contains the redox activity while the C-terminus exerts the DNA AP-endodeoxyribonuclease activity; both function are independent in their actions. An unconventional mitochondrial targeting sequence (MTS) is harbored within the C-terminus, that appears to be masked by the N-terminal sequence containing the nuclear localization signal (NLS), that probably blocks the interaction between the MTS and Tom proteins (By similarity).By similarity

Sequence similaritiesi

Belongs to the DNA repair enzymes AP/ExoA family.Curated

Phylogenomic databases

eggNOGiKOG1294. Eukaryota.
COG0708. LUCA.

Family and domain databases

Gene3Di3.60.10.10. 1 hit.
InterProiView protein in InterPro
IPR004808. AP_endonuc_1.
IPR020847. AP_endonuclease_F1_BS.
IPR020848. AP_endonuclease_F1_CS.
IPR036691. Endo/exonu/phosph_ase_sf.
IPR005135. Endo/exonuclease/phosphatase.
PANTHERiPTHR22748. PTHR22748. 1 hit.
PfamiView protein in Pfam
PF03372. Exo_endo_phos. 1 hit.
SUPFAMiSSF56219. SSF56219. 1 hit.
TIGRFAMsiTIGR00633. xth. 1 hit.
PROSITEiView protein in PROSITE
PS00726. AP_NUCLEASE_F1_1. 1 hit.
PS00727. AP_NUCLEASE_F1_2. 1 hit.
PS00728. AP_NUCLEASE_F1_3. 1 hit.
PS51435. AP_NUCLEASE_F1_4. 1 hit.


Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P43138-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
60 70 80 90 100
110 120 130 140 150
160 170 180 190 200
210 220 230 240 250
260 270 280 290 300
Mass (Da):35,538
Last modified:January 23, 2007 - v2

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti10Missing in AAA21019 (PubMed:7510394).Curated1
Sequence conflicti236R → A in AAA21019 (PubMed:7510394).Curated1
Sequence conflicti288H → Q in AAA21019 (PubMed:7510394).Curated1

Sequence databases

Select the link destinations:
Links Updated
L27076 mRNA. Translation: AAA21019.1.
AB023065 Genomic DNA. Translation: BAA82124.1.
D44495 mRNA. Translation: BAA07938.1.
AF309114 mRNA. Translation: AAG40859.1.
BC078816 mRNA. Translation: AAH78816.1.
RefSeqiNP_077062.1. NM_024148.1.
XP_006251975.1. XM_006251913.1.

Genome annotation databases

EnsembliENSRNOT00000013176; ENSRNOP00000013176; ENSRNOG00000009663.
ENSRNOT00000087958; ENSRNOP00000068673; ENSRNOG00000009663.
UCSCiRGD:2126. rat.

Similar proteinsi

Entry informationi

Entry nameiAPEX1_RAT
AccessioniPrimary (citable) accession number: P43138
Secondary accession number(s): Q548N9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 23, 2007
Last modified: November 22, 2017
This is version 163 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program


Keywords - Technical termi

Complete proteome, Reference proteome


  1. SIMILARITY comments
    Index of protein domains and families