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  3. APEX1

APEX1 (Apurinic/apyrimidinic endodeoxyribonuclease 1)

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The Function of APEX1

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 and Lys-7, 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.

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Protein names

Recommended name:

DNA-

Short name:

APEN

Alternative name(s):

apurinic or apyrimidinic site
APEX nuclease
Apurinic-apyrimidinic endonuclease 1
AP endonuclease 1
APE-1
REF-1
Redox factor-1
apurinic or apyrimidinic site

APEX1 SNPs

    To see your genotype, you should be logged in and have a file with your genotype uploaded.

  1. RS1130409 (APEX1) ??
  2. RS1760944 (APEX1) ??
  3. RS3136814 (APEX1) ??
  4. RS3136817 (APEX1) ??

Top Gene-Substance Interactions

APEX1 Interacts with These Diseases

Disease Score

Substances That Increase APEX1

Substances Interaction Organism Category

Substances That Decrease APEX1

Substances Interaction Organism Category

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • GR
  • GR-alpha
  • GR-beta
  • p53
  • Egr-1
  • CREB
  • AP-1
  • c-Jun
  • deltaCREB
  • p300

Gene Pathways:

  • Base excision repair
  • DNA Repair

Induction:

Up-regulated in presence of reactive oxygen species (ROS), like bleomycin, H(2)O(2) and phenazine methosulfate.

Enzyme Regulation:

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

Cofactor:

Probably binds two magnesium or manganese ions per subunit.

Molecular Function:

  • 3'-5' Exonuclease Activity
  • Chromatin Dna Binding
  • Damaged Dna Binding
  • Dna-(Apurinic Or Apyrimidinic Site) Lyase Activity
  • Dna Binding
  • Double-Stranded Dna 3'-5' Exodeoxyribonuclease Activity
  • Double-Stranded Dna Exodeoxyribonuclease Activity
  • Double-Stranded Telomeric Dna Binding
  • Endodeoxyribonuclease Activity
  • Endonuclease Activity
  • Metal Ion Binding
  • Oxidoreductase Activity
  • Phosphodiesterase I Activity
  • Phosphoric Diester Hydrolase Activity
  • Poly(A) Rna Binding
  • Rna-Dna Hybrid Ribonuclease Activity
  • Site-Specific Endodeoxyribonuclease Activity, Specific For Altered Base
  • Transcription Coactivator Activity
  • Transcription Corepressor Activity
  • Uracil Dna N-Glycosylase Activity

Biological Processes:

  • Aging
  • Base-Excision Repair
  • Base-Excision Repair, Base-Free Sugar-Phosphate Removal
  • Cell Redox Homeostasis
  • Cellular Response To Camp
  • Cellular Response To Hydrogen Peroxide
  • Cellular Response To Peptide Hormone Stimulus
  • Dna Demethylation
  • Dna Recombination
  • Dna Repair
  • Negative Regulation Of Smooth Muscle Cell Migration
  • Positive Regulation Of Dna Repair
  • Positive Regulation Of G1/S Transition Of Mitotic Cell Cycle
  • Regulation Of Mrna Stability
  • Regulation Of Transcription, Dna-Templated
  • Telomere Maintenance
  • Transcription, Dna-Templated

Drug Bank:

  • Lucanthone
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| APE| APE1| APEN| AP endonuclease 1| AP endonuclease class I| Apex| apex1a| APEX nuclease| APEX nuclease 1| APEX nuclease (multifunctional DNA repair enzyme) 1| AP lyase| apurinic/apyrimidinic (abasic) endonuclease| apurinic/apyrimidinic endonuclease| apurinic-apyrimidinic endonuclease 1| apurinic/apyrimidinic endonuclease 1| APX| BAP1| CB1_001481040| deoxyribonuclease (apurinic or apyrimidinic)| DNA-(apurinic or apyrimidinic site) lyase| DNA-apurinic or apyrimidinic site lyase| DNA-(apurinic or apyrimidinic site) lyase-like protein| EGK_17940| GW7_14830| HAP1| MDA_GLEAN10005572| N301_04481| N303_00031| PANDA_019762| protein REF-1| redox factor-1| Ref-1| REF1| TREES_T100011131| UY3_18656| Y1Q_010152| zap1| apex1

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