Search Results
Overview
| Uniprot ID | P27695 |
|---|---|
| Protein Name | DNA repair nuclease/redox regulator APEX1 |
| Gene Name | APEX1 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 197 | EAFRKFLKGLASRKP |
| 228 | RNPKGNKKNAGFTPQ |
| 24 | LRTEPEAKKSKTAAK |
| 276 | YMMNARSKNVGWRLD |
| 32 | KSKTAAKKNDKEAAG |
| 35 | TAAKKNDKEAAGEGP |
| 7 | *MPKRGKKGAVAEDG |
| 98 | ILCLQETKCSENKLP |
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 (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)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Cellular Component | GO:0000781 | chromosome, telomeric region |
| Cellular Component | GO:0005737 | cytoplasm |
| Cellular Component | GO:0005783 | endoplasmic reticulum |
| Cellular Component | GO:0005739 | mitochondrion |
| Cellular Component | GO:0016607 | nuclear speck |
| Cellular Component | GO:0005730 | nucleolus |
| Cellular Component | GO:0005654 | nucleoplasm |
| Cellular Component | GO:0005634 | nucleus |
| Cellular Component | GO:0048471 | perinuclear region of cytoplasm |
| Cellular Component | GO:0005840 | ribosome |
| Molecular Function | GO:0008408 | 3'-5' exonuclease activity |
| Molecular Function | GO:0008296 | 3'-5'-DNA exonuclease activity |
| Molecular Function | GO:0031490 | chromatin DNA binding |
| Molecular Function | GO:0052720 | class II DNA-(apurinic or apyrimidinic site) endonuclease activity |
| Molecular Function | GO:0003684 | damaged DNA binding |
| Molecular Function | GO:0033892 | deoxyribonuclease (pyrimidine dimer) activity |
| Molecular Function | GO:0003677 | DNA binding |
| Molecular Function | GO:0004520 | DNA endonuclease activity |
| Molecular Function | GO:0140431 | DNA-(abasic site) binding |
| Molecular Function | GO:0003906 | DNA-(apurinic or apyrimidinic site) endonuclease activity |
| Molecular Function | GO:0008311 | double-stranded DNA 3'-5' DNA exonuclease activity |
| Molecular Function | GO:0008309 | double-stranded DNA exodeoxyribonuclease activity |
| Molecular Function | GO:0003691 | double-stranded telomeric DNA binding |
| Molecular Function | GO:0004519 | endonuclease activity |
| Molecular Function | GO:0046872 | metal ion binding |
| Molecular Function | GO:0016491 | oxidoreductase activity |
| Molecular Function | GO:0090580 | phosphodiesterase activity, acting on 3'-phosphoglycolate-terminated DNA strands |
| Molecular Function | GO:0004528 | phosphodiesterase I activity |
| Molecular Function | GO:0008081 | phosphoric diester hydrolase activity |
| Molecular Function | GO:0003723 | RNA binding |
| Molecular Function | GO:0004523 | RNA-DNA hybrid ribonuclease activity |
| Molecular Function | GO:0003713 | transcription coactivator activity |
| Molecular Function | GO:0003714 | transcription corepressor activity |
| Molecular Function | GO:0004844 | uracil DNA N-glycosylase activity |
| Biological Process | GO:0006284 | base-excision repair |
| Biological Process | GO:0006287 | base-excision repair, gap-filling |
| Biological Process | GO:0006308 | DNA catabolic process |
| Biological Process | GO:0006310 | DNA recombination |
| Biological Process | GO:0006281 | DNA repair |
| Biological Process | GO:0044029 | positive regulation of gene expression via chromosomal CpG island demethylation |
| Biological Process | GO:0045944 | positive regulation of transcription by RNA polymerase II |
| Biological Process | GO:0042981 | regulation of apoptotic process |
| Biological Process | GO:0043488 | regulation of mRNA stability |
| Biological Process | GO:0000723 | telomere maintenance |
| Biological Process | GO:0097698 | telomere maintenance via base-excision repair |
Reference
[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.
[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[3] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.
[4] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.
[5] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.
[6] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.
[7] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.