| 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 an 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. Also incises 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 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses 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 protection from granzyme-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. |
| Protein Name | Dna Repair Nuclease/Redox Regulator Apex1Apex NucleaseApenApurinic-Apyrimidinic Endonuclease 1Ap Endonuclease 1Ape-1Dna-(Apurinic Or Apyrimidinic Site EndonucleaseRedox Factor-1Ref-1 Cleaved Into - Dna Repair Nuclease/Redox Regulator Apex1 - Mitochondrial |
| Database Links | Reactome: R-HSA-110357Reactome: R-HSA-110362Reactome: R-HSA-110373Reactome: R-HSA-5651801Reactome: R-HSA-73930Reactome: R-HSA-73933 |
| Cellular Localisation | NucleusNucleolusNucleus SpeckleEndoplasmic ReticulumCytoplasmDetected In The Cytoplasm Of B-Cells Stimulated To SwitchColocalized With Sirt1 In The NucleusColocalized With Ybx1 In Nuclear Speckles After Genotoxic StressTogether With Ogg1 Is Recruited To Nuclear Speckles In Uva-Irradiated CellsColocalized With Nucleolin And Npm1 In The NucleolusIts Nucleolar Localization Is Cell Cycle Dependent And Requires Active Rrna TranscriptionColocalized With Calreticulin In The Endoplasmic ReticulumTranslocation From The Nucleus To The Cytoplasm Is Stimulated In Presence Of Nitric Oxide (No) And Function In A Crm1-Dependent MannerPossibly As A Consequence Of Demasking A Nuclear Export Signal (Amino Acid Position 64-80)S-Nitrosylation At Cys-93 And Cys-310 Regulates Its Nuclear-Cytosolic ShuttlingUbiquitinated Form Is Localized Predominantly In The CytoplasmDna Repair Nuclease/Redox Regulator Apex1Mitochondrial: MitochondrionThe Cleaved Apex2 Is Only Detected In MitochondriaTranslocation From The Cytoplasm To The Mitochondria Is Mediated By Ros Signaling And Cleavage Mediated By Granzyme ATom20-Dependent Translocated Mitochondrial Apex1 Level Is Significantly Increased After Genotoxic Stress |
| Alternative Protein Names | Dna Repair Nuclease/Redox Regulator Apex1 proteinApex Nuclease proteinApen proteinApurinic-Apyrimidinic Endonuclease 1 proteinAp Endonuclease 1 proteinApe-1 proteinDna-(Apurinic Or Apyrimidinic Site Endonuclease proteinRedox Factor-1 proteinRef-1 Cleaved Into - Dna Repair Nuclease/Redox Regulator Apex1 - Mitochondrial proteinAPEX1 proteinAPE proteinAPE1 proteinAPEX proteinAPX proteinHAP1 proteinREF1 protein |
Information sourced from Uniprot.org
