Summary

Name APEX1
Full Name DNA-
Synonyms APEX nuclease, APEN, Apurinic-apyrimidinic endonuclease 1, AP endonuclease 1, APE-1, REF-1, Redox factor-1 | APE, APE1, APEX, APX, HAP1, REF1
Primary ID P27695
Links - -
Type protein
Relations 7
Function Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 are 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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▶Modifications Tables

Relations

Regulator Mechanism target score ℹ
+ CSNK2A1up-regulates activity img/direct-activation.png phosphorylation APEX1 0.499
Publications: 1 Organism: Chlorocebus Aethiops
+ CDK5up-regulates activity img/direct-activation.png phosphorylation APEX1 0.387
Publications: 1 Organism: Homo Sapiens
+ APEX1up-regulates quantity by expression img/direct-activation.png transcriptional regulation TG 0.2
Publications: 1
+ ERCC6down-regulates activity img/direct_inhibition.png binding APEX1 0.429
Publications: 1 Organism: Homo Sapiens
+ APEX1up-regulates quantity by expression img/direct-activation.png transcriptional regulation SLC5A5 0.2
Publications: 1 Organism: Homo Sapiens
+ APEX1down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation CYP11B2 0.351
Publications: 1 Organism: Homo Sapiens
+ APEX1up-regulates img/indirect-activation.png Base-excision_repair 0.7
Publications: 1