Monomer. Homodimer; disulfide-linked. Component of the SET complex, composed at least of APEX1, GZMA, SET, ANP32A, HMGB2 and NME1. 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 at Lys-6 and Lys-7. 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.
Function:
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 to 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.
Subcellular Location:
DNA-(apurinic or apyrimidinic site) lyase, mitochondrial
Mitochondrion
The cleaved APEX2 is only detected in mitochondria (By similarity). Translocation from the cytoplasm to the mitochondria is mediated by ROS signaling and cleavage mediated by granzyme A. Tom20-dependent translocated mitochondrial APEX1 level is significantly increased after genotoxic stress.
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Cited for: NUCLEOTIDE SEQUENCE [MRNA];PROTEIN SEQUENCE OF 2-21
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]
11.
NIEHS SNPs program
Submitted (2002-02) to the EMBL/GenBank/DDBJ databases
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Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA];VARIANTS HIS-51; VAL-64 AND GLU-148
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA];VARIANT GLU-148
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Cited for: PROTEIN SEQUENCE OF 2-10;FUNCTION;INTERACTION WITH GZMA;CLEAVAGE BY GRANZYME A;IDENTIFICATION IN THE SET COMPLEX;MUTAGENESIS OF LYS-31; CYS-65 AND ASP-210;SUBCELLULAR LOCATION
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Cited for: FUNCTION;MUTAGENESIS OF CYS-65; CYS-93; CYS-99; CYS-138; CYS-208; CYS-296 AND CYS-310
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Cited for: FUNCTION;SUBUNIT;INTERACTION WITH TXN;SUBCELLULAR LOCATION
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Cited for: CATALYTIC ACTIVITY;FUNCTION;MUTAGENESIS OF ASP-283; ASP-308 AND HIS-309;COFACTOR
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Cited for: FUNCTION;PHOSPHORYLATION BY CKII;SUBCELLULAR LOCATION
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Cited for: INTERACTION WITH HDAC1; HDAC2 AND HDAC3;ACETYLATION AT LYS-6 AND LYS-7;MUTAGENESIS OF LYS-6 AND LYS-7
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Cited for: CATALYTIC ACTIVITY;ACTIVE SITE;MUTAGENESIS OF TYR-171
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Cited for: INTERACTION WITH KPNA1 AND KPNA2;MUTAGENESIS OF LYS-6; LYS-7; GLU-12 AND ASP-13;SUBCELLULAR LOCATION
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Cited for: S-NITROSYLATION AT CYS-65; CYS-93 AND CYS-310 IN RESPONSE TO NITRIC OXIDE;SUBCELLULAR LOCATION
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Cited for: FUNCTION;INTERACTION WITH MVP AND YBX1;MUTAGENESIS OF LYS-6 AND LYS-7;SUBCELLULAR LOCATION
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Cited for: FUNCTION;MUTAGENESIS OF CYS-65; CYS-93; CYS-99; CYS-138; CYS-208; CYS-296 AND CYS-310
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Cited for: FUNCTION;INTERACTION WITH KRT8; NPM1; PRDX6; PRPF19; RPLP0 AND WDR77;RNA-BINDING;SUBCELLULAR LOCATION
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Cited for: FUNCTION;RNA-BINDING;MUTAGENESIS OF GLU-96 AND HIS-309
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Cited for: INTERACTION WITH MDM2;UBIQUITINATION;MUTAGENESIS OF LYS-24; LYS-25 AND LYS-27
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Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-197;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: INTERACTION WITH TOMM20;MUTAGENESIS OF LYS-24; LYS-25; LYS-27; LYS-31; LYS-299; ARG-301 AND LYS-303;SUBCELLULAR LOCATION
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Cited for: FUNCTION;INTERACTION WITH SIRT1 AND XRCC1;MUTAGENESIS OF LYS-6 AND LYS-7;SUBCELLULAR LOCATION
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Cited for: FUNCTION;INTERACTION WITH NPM1;RNA-BINDING;ACETYLATION AT LYS-27; LYS-31; LYS-32 AND LYS-35;MUTAGENESIS OF LYS-24; LYS-25; LYS-27; LYS-31 AND LYS-32;IDENTIFICATION BY MASS SPECTROMETRY
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Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: MUTAGENESIS OF ASN-68; ASP-70; TYR-171; PHE-266; ASP-283; ASP-308 AND HIS-309;CATALYTIC ACTIVITY;ACTIVE SITE;FUNCTION;COFACTOR
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Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 32-318 IN COMPLEX WITH METAL IONS
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Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 40-318 IN COMPLEX WITH DNA AND METAL ION;DNA-BINDING
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Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH METAL IONS;CATALYTIC ACTIVITY;COFACTOR