a multifunctional enzyme that plays a central role in the cellular response to oxidative stress including DNA repair and redox regulation of transcriptional factors. Binds DNA and RNA. Functions as an apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway, a 3'-5' exoribonuclease for mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules, and a DNA 3' phosphodiesterase capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. Is a loading factor for POLB onto non-incised AP sites in DNA, stimulates the 5'-terminal deoxyribose 5'- phosphate (dRp) excision activity of POLB, and involved in the DNA cleavage step of class switch recombination (CSR). Possesses 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. Binds to negative calcium response elements (nCaREs). Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Is an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover. In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. 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. Up-regulated in presence of reactive oxygen species (ROS), like bleomycin, H2O2 and phenazine methosulfate. NPM1 stimulates endodeoxyribonuclease activity on double-stranded DNA with AP sites, but inhibits endoribonuclease activity on single-stranded RNA containing AP sites. Belongs to the DNA repair enzymes AP/ExoA family. Note: This description may include information from UniProtKB.
Protein type: Hydrolase; Lyase; Transcription, coactivator/corepressor; Nuclear receptor co-regulator; DNA repair, damage; Nucleolus; EC 184.108.40.206; Deoxyribonuclease; Endoplasmic reticulum; DNA binding protein
Chromosomal Location of Human Ortholog: 14q11.2
Cellular Component: nucleoplasm; centrosome; transcription factor complex; mitochondrion; endoplasmic reticulum; perinuclear region of cytoplasm; cytoplasm; nucleolus; ribosome; nuclear speck; nucleus
Molecular Function: phosphodiesterase I activity; DNA-(apurinic or apyrimidinic site) lyase activity; phosphoric diester hydrolase activity; uracil DNA N-glycosylase activity; chromatin DNA binding; metal ion binding; transcription coactivator activity; oxidoreductase activity; endodeoxyribonuclease activity; NF-kappaB binding; protein binding; DNA binding; endonuclease activity; damaged DNA binding; protein complex binding; ribonuclease H activity; 3'-5' exonuclease activity; double-stranded DNA specific 3'-5' exodeoxyribonuclease activity; transcription corepressor activity; site-specific endodeoxyribonuclease activity, specific for altered base
Biological Process: response to drug; positive regulation of DNA repair; mismatch repair; transcription, DNA-dependent; negative regulation of smooth muscle cell migration; DNA strand elongation during DNA replication; DNA repair; regulation of mRNA stability; DNA catabolic process, endonucleolytic; double-strand break repair via homologous recombination; telomere maintenance via semi-conservative replication; regulation of transcription, DNA-dependent; cell redox homeostasis; nucleotide-excision repair; base-excision repair; double-strand break repair; transcription-coupled nucleotide-excision repair; telomere maintenance via recombination; nucleotide-excision repair, DNA gap filling; mitotic cell cycle; DNA catabolic process, exonucleolytic; telomere maintenance; aging
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.