Recombinant Human APE1 protein (T7 tag N-Terminus)

일반 정보

기능

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 (PubMed : 11118054, PubMed : 11452037, PubMed : 15831793, PubMed : 18439621, PubMed : 18579163, PubMed : 21762700, PubMed : 24079850, PubMed : 8355688, PubMed : 9108029, PubMed : 9560228). Functions as an apurinic/apyrimidinic (AP) endodeoxyribonuclease in the 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 (PubMed : 15380100, PubMed : 16617147, PubMed : 18439621, PubMed : 19123919, PubMed : 19188445, PubMed : 19934257, PubMed : 20699270, PubMed : 21762700, PubMed : 24079850, PubMed : 8932375, PubMed : 8995436, PubMed : 9804799). Operates at switch sites of immunoglobulin (Ig) constant regions where it mediates Ig isotype class switch recombination. Processes AP sites induced by successive action of AICDA and UNG. Generates staggered nicks in opposite DNA strands resulting in the formation of double-strand DNA breaks that are finally resolved via non-homologous end joining repair pathway (By similarity). Has 3'-5' exodeoxyribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER (PubMed : 11832948, PubMed : 1719477). Possesses DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate and 8-oxoguanine) blocking the 3' side of DNA strand breaks (PubMed : 15831793, PubMed : 7516064). Also acts 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 (PubMed : 19188445, PubMed : 19401441, PubMed : 21762700). 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 (PubMed : 9207062). 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 (PubMed : 10023679, PubMed : 11118054, PubMed : 11452037, PubMed : 18579163, PubMed : 8355688, PubMed : 9108029). 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 (PubMed : 11809897, PubMed : 14633989, PubMed : 8621488). May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation (PubMed : 21496894). Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance (PubMed : 18809583). Plays a role in protection from granzyme-mediated cellular repair leading to cell death (PubMed : 18179823). Binds DNA and RNA. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA (PubMed : 19188445, PubMed : 19401441, PubMed : 20699270).

서열 유사성

Belongs to the DNA repair enzymes AP/ExoA family.

Post-translational modifications

Phosphorylated. Phosphorylation by kinase PKC or casein kinase CK2 results in enhanced redox activity that stimulates binding of the FOS/JUN AP-1 complex to its cognate binding site. AP-endodeoxyribonuclease activity is not affected by CK2-mediated phosphorylation. Phosphorylation of Thr-233 by CDK5 reduces AP-endodeoxyribonuclease activity resulting in accumulation of DNA damage and contributing to neuronal death.. Acetylated on Lys-6 and Lys-7. Acetylation is increased by the transcriptional coactivator EP300 acetyltransferase, genotoxic agents like H(2)O(2) and methyl methanesulfonate (MMS). Acetylation increases its binding affinity to the negative calcium response element (nCaRE) DNA promoter. The acetylated form induces a stronger binding of YBX1 to the Y-box sequence in the MDR1 promoter than the unacetylated form. Deacetylated on lysines. Lys-6 and Lys-7 are deacetylated by SIRT1.. Cleaved at Lys-31 by granzyme A to create the mitochondrial form; leading to reduction of binding to DNA, AP endodeoxynuclease activity, redox activation of transcription factors and to enhanced cell death. Cleaved by granzyme K; leading to intracellular ROS accumulation and enhanced cell death after oxidative stress.. Cys-65 and Cys-93 are nitrosylated in response to nitric oxide (NO) and lead to the exposure of the nuclear export signal (NES).. Ubiquitinated by MDM2; leading to translocation to the cytoplasm and proteasomal degradation.

Subcellular localisation

Nucleus