APEX1 (also known as APE1, HAP1, REF-1) is a multifunctional protein that plays a central role in the cellular response to oxidative stress. It has two major independent activities: (1) DNA repair as the principal AP endonuclease in the base excision repair (BER) pathway, and (2) redox regulation of transcription factors. As an AP endonuclease, APEX1 incises DNA at abasic sites, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. It also has 3'-5' exonuclease activity on mismatched DNA termini and 3'-phosphodiesterase activity that removes blocking groups such as phosphoglycolate and 8-oxoguanine. The redox function, mediated by the N-terminal domain, reduces critical cysteines on transcription factors (HIF-1alpha, NF-kappaB, AP-1, p53) to enhance their DNA binding activity. APEX1 also functions as an endoribonuclease on single-stranded RNA, regulating mRNA stability.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: APEX1 is predominantly localized in the nucleus where it performs its DNA repair and transcriptional regulation functions. Multiple IDA studies confirm nuclear localization (PMID:9119221, PMID:15942031, PMID:19934257, PMID:28404743). Reason: Nuclear localization is well-established for APEX1. The protein contains a nuclear localization signal (NLS) at positions 8-13 and is detected in the nucleus, nucleoplasm, and nucleolus under normal conditions. This is a core cellular component annotation. Supporting Evidence: PMID:15942031 Analysis of nuclear transport signals in the human apurinic/apyrimidinic endonuclease (APE1/Ref1) PMID:9119221 Identification of redox/repair protein Ref-1 as a potent activator of p53 file:human/APEX1/APEX1-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0006284 base-excision repair | IBA GO_REF:0000033 | ACCEPT | Summary: APEX1 is the major human AP endonuclease in base excision repair. It functions downstream of DNA glycosylases, cleaving the phosphodiester backbone at AP sites to initiate repair synthesis. Reason: Base excision repair is the primary biological process function of APEX1. The protein is essential for BER and coordinates with PARP1, XRCC1, and DNA polymerase beta in this pathway. This is a core function annotation. Supporting Evidence: PMID:8932386 Drosophila ribosomal protein PO contains apurinic/apyrimidinic endonuclease activity [demonstrates conservation of BER function] PMID:1627644 cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III |
| GO:0008081 phosphoric diester hydrolase activity | IBA GO_REF:0000033 | ACCEPT | Summary: APEX1 has phosphodiester hydrolase activity, cleaving the phosphodiester bond 5' to an AP site in DNA. This activity is also used for 3'-end processing at single-strand breaks. Reason: This molecular function accurately describes one of APEX1's core enzymatic activities. The protein hydrolyzes phosphodiester bonds in DNA substrates containing abasic sites or 3'-blocking groups. Supporting Evidence: PMID:11478795 Sequence analysis identifies TTRAP, a protein that associates with CD40 and TNF receptor-associated factors, as a member of a superfamily of divalent cation-dependent phosphodiesterases PMID:18973764 Human ribosomal protein S3 (hRpS3) interacts with uracil-DNA glycosylase (hUNG) and stimulates its glycosylase activity |
| GO:0003906 DNA-(apurinic or apyrimidinic site) endonuclease activity | IBA GO_REF:0000033 | ACCEPT | Summary: AP endonuclease activity is the defining core function of APEX1. The enzyme incises DNA at AP sites, generating 3'-OH and 5'-dRP termini for downstream BER processing. Reason: This is the primary molecular function of APEX1 (hence the name APE1/APEX1). The enzyme is class II AP endonuclease that cleaves 5' to the AP site. Multiple crystal structures and enzymatic studies confirm this activity. Supporting Evidence: PMID:11286553 Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic mechanism PMID:9804798 Dynamics of the interaction of human apurinic endonuclease (Ape1) with its substrate and product |
| GO:0008311 double-stranded DNA 3'-5' DNA exonuclease activity | IBA GO_REF:0000033 | ACCEPT | Summary: APEX1 has 3'-5' exonuclease activity that removes mismatched nucleotides from the 3' terminus of nicked or gapped DNA during BER short-patch repair. Reason: The 3'-5' exonuclease activity of APEX1 is well-documented and represents a secondary enzymatic function important for proofreading during BER. Supporting Evidence: PMID:11832948 An exonucleolytic activity of human apurinic/apyrimidinic endonuclease on 3' mispaired DNA PMID:1627644 cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III |
| GO:0045892 negative regulation of DNA-templated transcription | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: This annotation is inferred from APEX1's transcription corepressor activity. APEX1/Ref-1 can act as a transcriptional repressor by binding to negative calcium response elements (nCaRE) together with HNRNPL or Ku proteins. Reason: While APEX1 can function in transcriptional repression (e.g., PTH gene regulation), this is a secondary function compared to its core DNA repair and redox coactivator roles. The term is appropriate but represents a non-core function. Supporting Evidence: PMID:7961715 A redox factor protein, ref1, is involved in negative gene regulation by extracellular calcium PMID:11809897 Human AP-endonuclease 1 and hnRNP-L interact with a nCaRE-like repressor element in the AP-endonuclease 1 promoter |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: APEX1 binds DNA as part of its AP endonuclease function, recognizing and binding to abasic sites in duplex DNA. Reason: DNA binding is essential for APEX1's enzymatic function. The protein binds damaged DNA containing AP sites with high specificity. This is a core molecular function annotation. Supporting Evidence: PMID:11286553 Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1 |
| GO:0003723 RNA binding | IEA GO_REF:0000043 | ACCEPT | Summary: APEX1 has RNA binding activity, particularly in the context of its endoribonuclease function and interaction with rRNA in nucleoli. Reason: RNA binding is a documented function of APEX1. The N-terminal domain (residues 2-33) is necessary for RNA binding and endoribonuclease activity on single-stranded RNA. APEX1 associates with rRNA together with NPM1. Supporting Evidence: PMID:19188445 APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process PMID:19401441 Identification of Apurinic/apyrimidinic endonuclease 1 (APE1) as the endoribonuclease that cleaves c-myc mRNA |
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | ACCEPT | Summary: APEX1 is a multifunctional enzyme with AP endonuclease, exonuclease, and phosphodiesterase activities. Reason: This general term is correct but redundant given the more specific enzymatic activity annotations. It serves as a parent term for the specific catalytic activities of APEX1. Supporting Evidence: PMID:11286553 Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic mechanism |
| GO:0004518 nuclease activity | IEA GO_REF:0000120 | ACCEPT | Summary: APEX1 has nuclease activity, functioning as both an endonuclease (at AP sites) and exonuclease (3'-5' direction). Reason: This is a correct parent term for APEX1's endonuclease and exonuclease activities. The protein cleaves DNA phosphodiester bonds at specific sites. Supporting Evidence: PMID:1627644 cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III |
| GO:0004519 endonuclease activity | IEA GO_REF:0000120 | ACCEPT | Summary: APEX1 functions as a DNA endonuclease, cleaving internal phosphodiester bonds at abasic sites. Reason: Endonuclease activity is a core molecular function of APEX1. The protein is the major AP endonuclease in human cells. Supporting Evidence: PMID:11478795 Sequence analysis identifies TTRAP, a protein that associates with CD40 and TNF receptor-associated factors, as a member of a superfamily of divalent cation-dependent phosphodiesterases PMID:1722334 Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: definition of a family of DNA repair enzymes |
| GO:0004527 exonuclease activity | IEA GO_REF:0000043 | ACCEPT | Summary: APEX1 has 3'-5' exonuclease activity that removes mismatched nucleotides from the 3' terminus of DNA. Reason: Exonuclease activity is a documented function of APEX1, important for proofreading during BER. Supporting Evidence: PMID:11832948 An exonucleolytic activity of human apurinic/apyrimidinic endonuclease on 3' mispaired DNA |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of IBA nucleus annotation. APEX1 is primarily nuclear. Reason: Nuclear localization is well-established. This IEA annotation is consistent with multiple IDA annotations and the IBA annotation. Supporting Evidence: PMID:9119221 Identification of redox/repair protein Ref-1 as a potent activator of p53 |
| GO:0005730 nucleolus | IEA GO_REF:0000044 | ACCEPT | Summary: APEX1 localizes to the nucleolus where it participates in rRNA quality control together with NPM1. Reason: Nucleolar localization is confirmed by IDA studies. APEX1's nucleolar localization is cell cycle dependent and requires active rRNA transcription. Supporting Evidence: PMID:19188445 APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process PMID:17148573 UVA irradiation induces relocalisation of the DNA repair protein hOGG1 to nuclear speckles |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: APEX1 can be detected in the cytoplasm under certain conditions, though it is predominantly nuclear. Reason: Cytoplasmic localization of APEX1 is documented, particularly in response to nitric oxide signaling or ubiquitination. This represents regulated nuclear-cytoplasmic shuttling. Supporting Evidence: PMID:9560228 Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species and its correlation with their adaptive response to genotoxicity of free radicals |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: A cleaved form of APEX1 (lacking N-terminal 31 residues) localizes to mitochondria where it participates in mitochondrial DNA repair. Reason: Mitochondrial localization is confirmed by IDA studies. APEX1 contains a C-terminal mitochondrial targeting sequence that is normally masked by the N-terminal NLS. Supporting Evidence: PMID:20231292 Identification and characterization of mitochondrial targeting sequence of human apurinic/apyrimidinic endonuclease 1 |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: APEX1 has been detected in the endoplasmic reticulum by colocalization with calreticulin. Reason: ER localization is documented but represents a minor fraction of cellular APEX1. The functional significance at this location is less clear than nuclear localization. Supporting Evidence: PMID:12524539 Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A |
| GO:0006281 DNA repair | IEA GO_REF:0000120 | ACCEPT | Summary: APEX1 is a key DNA repair enzyme, functioning primarily in base excision repair. Reason: DNA repair is the primary biological function of APEX1. This is a valid parent term for the more specific BER annotation. Supporting Evidence: PMID:1627644 cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III PMID:9560228 Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species |
| GO:0006310 DNA recombination | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: APEX1 may participate in DNA recombination, particularly at immunoglobulin switch regions during class switch recombination. Reason: While APEX1 processes AP sites at Ig switch regions and may contribute to class switch recombination, this is a specialized function secondary to its core BER role. |
| GO:0006974 DNA damage response | IEA GO_REF:0000043 | ACCEPT | Summary: APEX1 participates in DNA damage response through its repair functions and role in ATM activation at single-strand breaks. Reason: DNA damage response is a valid biological process for APEX1. Recent studies show APEX1 is required for ATM activation at single-strand breaks and coordinates DDR signaling. |
| GO:0008311 double-stranded DNA 3'-5' DNA exonuclease activity | IEA GO_REF:0000003 | ACCEPT | Summary: Duplicate of IBA annotation for 3'-5' DNA exonuclease activity. Reason: This duplicates the IBA annotation with EC-based evidence. The activity is well-documented for APEX1. Supporting Evidence: PMID:11832948 An exonucleolytic activity of human apurinic/apyrimidinic endonuclease on 3' mispaired DNA |
| GO:0016607 nuclear speck | IEA GO_REF:0000044 | ACCEPT | Summary: APEX1 localizes to nuclear speckles, particularly after genotoxic stress. Reason: Nuclear speckle localization is confirmed by IDA studies. APEX1 colocalizes with YBX1 in nuclear speckles after genotoxic stress. Supporting Evidence: PMID:17148573 UVA irradiation induces relocalisation of the DNA repair protein hOGG1 to nuclear speckles |
| GO:0016787 hydrolase activity | IEA GO_REF:0000043 | ACCEPT | Summary: APEX1 is a hydrolase that cleaves phosphodiester bonds in DNA. Reason: This is a correct parent term for APEX1's nuclease activities. The enzyme hydrolyzes phosphodiester bonds. Supporting Evidence: PMID:11286553 Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1 |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | ACCEPT | Summary: APEX1 requires divalent metal ions (Mg2+ or Mn2+) for catalytic activity. Reason: Metal ion binding is essential for APEX1 catalysis. Crystal structures show two metal binding sites coordinated by Asp68, Glu96, Asp210, Asn212, Asp308, and His309. Supporting Evidence: PMID:11286553 Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic mechanism |
| GO:0005515 protein binding | IPI PMID:19934257 SIRT1 deacetylates APE1 and regulates cellular base excision... | MODIFY | Summary: APEX1 interacts with SIRT1, which deacetylates APEX1 and regulates BER activity. Reason: The generic term "protein binding" does not capture the specific functional interaction. APEX1-SIRT1 interaction regulates deacetylation and BER activity. A more specific term describing the regulatory interaction would be preferable. Proposed replacements: histone deacetylase binding Supporting Evidence: PMID:19934257 SIRT1 deacetylates APE1 and regulates cellular base excision repair |
| GO:0005515 protein binding | IPI PMID:20696907 Identification of RING finger protein 4 (RNF4) as a modulato... | KEEP AS NON CORE | Summary: High-throughput interaction study identifying RNF4 as APEX1 interactor. Reason: This is a high-throughput study identifying RNF4 interaction. The functional significance of this specific interaction for APEX1's core functions is unclear. Generic "protein binding" is not informative. Supporting Evidence: PMID:20696907 Identification of RING finger protein 4 (RNF4) as a modulator of DNA demethylation through a functional genomics screen |
| GO:0005515 protein binding | IPI PMID:20808282 A multiprotein complex necessary for both transcription and ... | KEEP AS NON CORE | Summary: APEX1 identified in multiprotein complex at beta-globin locus. Reason: This study describes APEX1 as part of a transcription/replication complex. While interesting, this is peripheral to APEX1's core functions. Supporting Evidence: PMID:20808282 A multiprotein complex necessary for both transcription and DNA replication at the beta-globin locus |
| GO:0005515 protein binding | IPI PMID:20856196 Human AP endonuclease (APE1/Ref-1) and its acetylation regul... | KEEP AS NON CORE | Summary: APEX1 interacts with EP300 (p300) and YBX1 in MDR1 gene activation. Reason: This interaction relates to APEX1's transcriptional coactivator function for MDR1 gene, which is a secondary function. Supporting Evidence: PMID:20856196 Human AP endonuclease (APE1/Ref-1) and its acetylation regulate YB-1-p300 recruitment and RNA polymerase II loading in the drug-induced activation of multidrug resistance gene MDR1 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: High-throughput interactome study identifying KLHL36 as APEX1 interactor. Reason: This is a large-scale interactome study. The functional significance of KLHL36 interaction is not established for APEX1 function. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks |
| GO:0005515 protein binding | IPI PMID:32911434 A functionally defined high-density NRF2 interactome reveals... | KEEP AS NON CORE | Summary: APEX1 interacts with NRF2, a transcription factor involved in oxidative stress response. Reason: NRF2 interaction may be relevant to APEX1's redox function but this is not its core DNA repair role. Supporting Evidence: PMID:32911434 A functionally defined high-density NRF2 interactome reveals new conditional regulators of ARE transactivation |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: High-throughput proteomics study of human interactome. Reason: Large-scale interactome study. Generic protein binding is not informative for understanding APEX1's specific functions. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome |
| GO:0005515 protein binding | IPI PMID:26760506 R152C DNA Pol Ξ² mutation impairs base excision repair and in... | MODIFY | Summary: APEX1 interacts with DNA polymerase beta (POLB) in the BER pathway. Reason: APEX1-POLB interaction is functionally important for BER coordination. APEX1 acts as a loading factor for POLB onto AP sites. A more specific term would better capture this functional interaction. Proposed replacements: DNA polymerase binding Supporting Evidence: PMID:9207062 Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway PMID:26760506 R152C DNA Pol beta mutation impairs base excision repair and induces cellular transformation |
| GO:0005515 protein binding | IPI PMID:9108029 AP-1 transcriptional activity is regulated by a direct assoc... | KEEP AS NON CORE | Summary: APEX1 interacts with thioredoxin (TXN) to regulate AP-1 DNA binding activity. Reason: The physical interaction with thioredoxin is experimentally supported, but the generic protein-binding term is not a core molecular activity. It should not be replaced by protein-disulfide reductase activity, which describes thioredoxin catalysis rather than APEX1's redox-regulatory function. Supporting Evidence: PMID:9108029 AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1 |
| GO:0005515 protein binding | IPI PMID:11118054 Thioredoxin nuclear translocation and interaction with redox... | KEEP AS NON CORE | Summary: APEX1 interacts with thioredoxin after ionizing radiation exposure. Reason: This is independent evidence for the same physical interaction with thioredoxin. Retain it as non-core rather than replacing it with protein-disulfide reductase activity, which is an activity of thioredoxin and not a binding function of APEX1. Supporting Evidence: PMID:11118054 Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation |
| GO:0005515 protein binding | IPI PMID:8621488 The interaction between Ku antigen and REF1 protein mediates... | KEEP AS NON CORE | Summary: APEX1 interacts with Ku70/Ku80 (XRCC5/XRCC6) heterodimer in transcriptional repression. Reason: APEX1-Ku interaction mediates transcriptional repression at nCaRE elements. This is a secondary function of APEX1. Supporting Evidence: PMID:8621488 The interaction between Ku antigen and REF1 protein mediates negative gene regulation by extracellular calcium |
| GO:0005515 protein binding | IPI PMID:15942031 Analysis of nuclear transport signals in the human apurinic/... | ACCEPT | Summary: APEX1 interacts with importins KPNA1 and KPNA2 for nuclear import. Reason: Importin interaction is necessary for APEX1 nuclear localization, which is essential for its function. This is functionally relevant. Supporting Evidence: PMID:15942031 Analysis of nuclear transport signals in the human apurinic/apyrimidinic endonuclease (APE1/Ref1) |
| GO:0005515 protein binding | IPI PMID:9207062 Interaction of human apurinic endonuclease and DNA polymeras... | ACCEPT | Summary: APEX1 interacts with DNA polymerase beta (POLB) in BER coordination. Reason: POLB interaction is central to APEX1's role in BER. APEX1 stimulates POLB's dRP lyase activity and coordinates substrate handoff. Supporting Evidence: PMID:9207062 Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway |
| GO:0005515 protein binding | IPI PMID:19465398 HMGA2 exhibits dRP/AP site cleavage activity and protects ca... | KEEP AS NON CORE | Summary: APEX1 interacts with HMGA2. Reason: The functional significance of HMGA2 interaction for APEX1's core functions is not established. Supporting Evidence: PMID:19465398 HMGA2 exhibits dRP/AP site cleavage activity and protects cancer cells from DNA-damage-induced cytotoxicity during chemotherapy |
| GO:0005515 protein binding | IPI PMID:19505873 Complementary quantitative proteomics reveals that transcrip... | KEEP AS NON CORE | Summary: APEX1 identified in AP-4 complex proteomics study. Reason: High-throughput proteomics identification. The specific functional role of this interaction is not characterized. Supporting Evidence: PMID:19505873 Complementary quantitative proteomics reveals that transcription factor AP-4 mediates E-box-dependent complex formation for transcriptional repression of HDM2 |
| GO:0005515 protein binding | IPI PMID:11809897 Human AP-endonuclease 1 and hnRNP-L interact with a nCaRE-li... | KEEP AS NON CORE | Summary: APEX1 interacts with hnRNP-L in transcriptional regulation at nCaRE. Reason: HNRNPL interaction is part of APEX1's transcriptional repressor function, which is secondary to its DNA repair role. Supporting Evidence: PMID:11809897 Human AP-endonuclease 1 and hnRNP-L interact with a nCaRE-like repressor element in the AP-endonuclease 1 promoter |
| GO:0005515 protein binding | IPI PMID:18809583 Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-... | KEEP AS NON CORE | Summary: APEX1 interacts with YBX1 and MVP in MDR1 transcriptional activation. Reason: YBX1 and MVP interactions relate to APEX1's transcriptional coactivator function for MDR1, which is a secondary function. Supporting Evidence: PMID:18809583 Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-1-mediated activation of the multidrug resistance gene MDR1 |
| GO:0005515 protein binding | IPI PMID:20231292 Identification and characterization of mitochondrial targeti... | ACCEPT | Summary: APEX1 interacts with TOMM20 for mitochondrial import. Reason: TOMM20 interaction is functionally important for APEX1's mitochondrial translocation and mtDNA repair function. Supporting Evidence: PMID:20231292 Identification and characterization of mitochondrial targeting sequence of human apurinic/apyrimidinic endonuclease 1 |
| GO:0005515 protein binding | IPI PMID:19188445 APE1/Ref-1 interacts with NPM1 within nucleoli and plays a r... | ACCEPT | Summary: APEX1 interacts with NPM1 in nucleolar rRNA quality control. Reason: NPM1 interaction is functionally important for APEX1's role in rRNA quality control in nucleoli. NPM1 modulates APEX1's enzymatic activities. Supporting Evidence: PMID:19188445 APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process |
| GO:0005515 protein binding | IPI PMID:15518571 Human ribosomal protein S3 interacts with DNA base excision ... | KEEP AS NON CORE | Summary: APEX1 interacts with ribosomal protein S3 (RPS3). Reason: RPS3 interaction may relate to APEX1's nucleolar functions but is not central to its core DNA repair role. Supporting Evidence: PMID:15518571 Human ribosomal protein S3 interacts with DNA base excision repair proteins hAPE/Ref-1 and hOGG1 |
| GO:0005515 protein binding | IPI PMID:12524539 Cleaving the oxidative repair protein Ape1 enhances cell dea... | KEEP AS NON CORE | Summary: APEX1 interacts with granzyme A, which cleaves APEX1 to generate the mitochondrial form. Reason: Granzyme A interaction leads to APEX1 cleavage and cell death enhancement. This is part of apoptotic signaling rather than APEX1's core repair function. Supporting Evidence: PMID:12524539 Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A |
| GO:0005634 nucleus | IDA PMID:19934257 SIRT1 deacetylates APE1 and regulates cellular base excision... | ACCEPT | Summary: APEX1 is predominantly localized in the nucleus where it performs its DNA repair and transcriptional regulation functions. This IDA annotation is based on experimental localization studies. Reason: Nuclear localization is well-established for APEX1. The protein contains a nuclear localization signal (NLS) and is detected in the nucleus under normal conditions. This is a core cellular component annotation supported by direct experimental evidence. Supporting Evidence: PMID:19934257 SIRT1 deacetylates APE1 and regulates cellular base excision repair |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: APEX1 localizes to the nucleoplasm based on immunofluorescence data. Reason: Nucleoplasm localization is consistent with APEX1's nuclear DNA repair function and is well-documented. Supporting Evidence: PMID:17148573 UVA irradiation induces relocalisation of the DNA repair protein hOGG1 to nuclear speckles |
| GO:0033892 deoxyribonuclease (pyrimidine dimer) activity | IDA PMID:19188445 APE1/Ref-1 interacts with NPM1 within nucleoli and plays a r... | REMOVE | Summary: This annotation appears to be an error. APEX1 is an AP endonuclease, not a pyrimidine dimer-specific nuclease. PMID:19188445 describes APE1's role in rRNA quality control, not pyrimidine dimer processing. Reason: This term (GO:0033892) describes nucleases that act on UV-induced pyrimidine dimers (like UV endonuclease). APEX1 does not have this activity. APEX1 cleaves at abasic sites and processes damaged 3' ends, not pyrimidine dimers. This appears to be an annotation error. Supporting Evidence: PMID:19188445 APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process [no mention of pyrimidine dimer activity] |
| GO:0033892 deoxyribonuclease (pyrimidine dimer) activity | IDA PMID:24703901 APE1 incision activity at abasic sites in tandem repeat sequ... | REMOVE | Summary: Duplicate annotation with same term. PMID:24703901 is about APE1 activity at telomeric sequences with abasic sites, not pyrimidine dimers. Reason: Same as above - APEX1 does not have pyrimidine dimer-specific nuclease activity. The cited paper describes APE1's AP endonuclease activity at tandem repeat sequences including telomeres. Supporting Evidence: PMID:24703901 APE1 incision activity at abasic sites in tandem repeat sequences |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: High-throughput mitochondrial proteome study confirming APEX1 localization. Reason: Mitochondrial localization is confirmed by multiple studies. APEX1 participates in mitochondrial DNA repair. Supporting Evidence: PMID:34800366 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context PMID:20231292 Identification and characterization of mitochondrial targeting sequence of human apurinic/apyrimidinic endonuclease 1 |
| GO:0044029 positive regulation of gene expression via chromosomal CpG island demethylation | IDA PMID:21496894 Hydroxylation of 5-methylcytosine by TET1 promotes active DN... | KEEP AS NON CORE | Summary: APEX1 participates in active DNA demethylation by processing abasic sites generated by TET-mediated oxidation followed by glycosylase removal. Reason: This represents a specialized role of APEX1 in epigenetic regulation through its AP endonuclease activity on demethylation intermediates. This is an extension of its core repair function to epigenetic modification. Supporting Evidence: PMID:21496894 Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain |
| GO:0006308 DNA catabolic process | IDA PMID:1627644 cDNA cloning, sequencing, expression and possible domain str... | ACCEPT | Summary: APEX1 has nuclease activities that result in DNA cleavage (phosphodiester hydrolysis at AP sites and 3'-5' exonuclease). Reason: DNA catabolic process accurately describes APEX1's nuclease function, though in the context of DNA repair rather than bulk DNA degradation. Supporting Evidence: PMID:1627644 cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III |
| GO:0052720 class II DNA-(apurinic or apyrimidinic site) endonuclease activity | IDA PMID:11160897 Enhanced activity of adenine-DNA glycosylase (Myh) by apurin... | ACCEPT | Summary: APEX1 is a class II AP endonuclease that cleaves 5' to the AP site, leaving a 3'-OH group. Reason: This is the specific AP endonuclease class for APEX1. Class II enzymes cleave via hydrolysis 5' to the AP site, in contrast to class I enzymes that use beta-elimination. Supporting Evidence: PMID:11160897 Enhanced activity of adenine-DNA glycosylase (Myh) by apurinic/apyrimidinic endonuclease (Ape1) in mammalian base excision repair of an A/GO mismatch |
| GO:0052720 class II DNA-(apurinic or apyrimidinic site) endonuclease activity | IDA PMID:11286553 Two divalent metal ions in the active site of a new crystal ... | ACCEPT | Summary: Structural study confirming class II AP endonuclease mechanism. Reason: Duplicate with different reference providing structural evidence for the class II mechanism. Supporting Evidence: PMID:11286553 Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic mechanism |
| GO:0052720 class II DNA-(apurinic or apyrimidinic site) endonuclease activity | IDA PMID:9804798 Dynamics of the interaction of human apurinic endonuclease (... | ACCEPT | Summary: Kinetic study of APE1 class II AP endonuclease mechanism. Reason: Additional evidence for class II AP endonuclease activity. Supporting Evidence: PMID:9804798 Dynamics of the interaction of human apurinic endonuclease (Ape1) with its substrate and product |
| GO:0140431 DNA-(abasic site) binding | IMP PMID:9804798 Dynamics of the interaction of human apurinic endonuclease (... | ACCEPT | Summary: APEX1 specifically binds to abasic sites in DNA as part of its recognition mechanism before catalysis. Reason: AP site binding is essential for APEX1's endonuclease function. The protein has high affinity and specificity for abasic DNA. Supporting Evidence: PMID:9804798 Dynamics of the interaction of human apurinic endonuclease (Ape1) with its substrate and product |
| GO:0006281 DNA repair | IDA PMID:1627644 cDNA cloning, sequencing, expression and possible domain str... | ACCEPT | Summary: Core DNA repair function of APEX1 established in early characterization. Reason: DNA repair is the primary biological function of APEX1. Supporting Evidence: PMID:1627644 cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III |
| GO:0008296 3'-5'-DNA exonuclease activity | IDA PMID:1627644 cDNA cloning, sequencing, expression and possible domain str... | ACCEPT | Summary: APEX1 has 3'-5' DNA exonuclease activity for proofreading mismatched 3' termini. Reason: This is a documented enzymatic activity of APEX1, important for removing mismatched nucleotides during BER. Supporting Evidence: PMID:1627644 cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III |
| GO:0052720 class II DNA-(apurinic or apyrimidinic site) endonuclease activity | IDA PMID:1627644 cDNA cloning, sequencing, expression and possible domain str... | ACCEPT | Summary: Original characterization of APEX1 as class II AP endonuclease. Reason: Core molecular function annotation. Supporting Evidence: PMID:1627644 cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III |
| GO:0090580 phosphodiesterase activity, acting on 3'-phosphoglycolate-terminated DNA strands | IDA PMID:1627644 cDNA cloning, sequencing, expression and possible domain str... | ACCEPT | Summary: APEX1 has 3'-phosphodiesterase activity that removes 3'-blocking groups including phosphoglycolate from DNA strand breaks. Reason: This is a specific 3'-end processing activity of APEX1 important for repairing oxidative DNA damage. Supporting Evidence: PMID:1627644 cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III. |
| GO:0003713 transcription coactivator activity | IDA PMID:18809583 Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-... | ACCEPT | Summary: APEX1 (Ref-1) functions as a transcription coactivator by reducing transcription factors and enhancing their DNA binding. Reason: Transcription coactivator activity via redox regulation is a core function of APEX1/Ref-1. This activity is mediated by the N-terminal redox domain. Supporting Evidence: PMID:18809583 Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-1-mediated activation of the multidrug resistance gene MDR1 |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:18809583 Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-... | ACCEPT | Summary: APEX1 positively regulates RNA Pol II transcription through its coactivator function. Reason: This is a valid biological process annotation for APEX1's transcriptional coactivator function. Supporting Evidence: PMID:18809583 Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-1-mediated activation of the multidrug resistance gene MDR1 |
| GO:0042981 regulation of apoptotic process | IDA PMID:19934257 SIRT1 deacetylates APE1 and regulates cellular base excision... | KEEP AS NON CORE | Summary: APEX1 regulates apoptosis through its interaction with SIRT1 and role in DNA damage response. Reason: Apoptosis regulation is a downstream consequence of APEX1's DNA repair function rather than a core function. Loss of APEX1 leads to increased apoptosis due to accumulated DNA damage. Supporting Evidence: PMID:19934257 SIRT1 deacetylates APE1 and regulates cellular base excision repair |
| GO:0097698 telomere maintenance via base-excision repair | IDA PMID:24703901 APE1 incision activity at abasic sites in tandem repeat sequ... | ACCEPT | Summary: APEX1 processes abasic sites in telomeric DNA to maintain telomere integrity. Reason: This is a specialized application of APEX1's BER function to telomeric sequences, which accumulate oxidative damage. Supporting Evidence: PMID:24703901 APE1 incision activity at abasic sites in tandem repeat sequences |
| GO:0005634 nucleus | IDA PMID:28404743 Nuclear complex of glyceraldehyde-3-phosphate dehydrogenase ... | ACCEPT | Summary: Additional IDA evidence for nuclear localization. Reason: Consistent with other evidence for nuclear localization. Supporting Evidence: PMID:28404743 Nuclear complex of glyceraldehyde-3-phosphate dehydrogenase and DNA repair enzyme apurinic/apyrimidinic endonuclease I protect smooth muscle cells against oxidant-induced cell death |
| GO:0003906 DNA-(apurinic or apyrimidinic site) endonuclease activity | IDA PMID:8932386 Drosophila ribosomal protein PO contains apurinic/apyrimidin... | ACCEPT | Summary: Note: This PMID is about Drosophila ribosomal protein P0, not directly APEX1. The citation may be used for comparative evidence. Reason: AP endonuclease activity is the core function of APEX1. Multiple other PMIDs directly demonstrate this activity. Supporting Evidence: PMID:11286553 Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1 PMID:8932386 Drosophila ribosomal protein PO contains apurinic/apyrimidinic endonuclease activity. |
| GO:0006284 base-excision repair | IDA PMID:8932386 Drosophila ribosomal protein PO contains apurinic/apyrimidin... | ACCEPT | Summary: BER function of APEX1 demonstrated through comparative studies. Reason: BER is the core biological process function of APEX1. Supporting Evidence: PMID:1627644 cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III PMID:8932386 Drosophila ribosomal protein PO contains apurinic/apyrimidinic endonuclease activity. |
| GO:0000723 telomere maintenance | IDA PMID:24703901 APE1 incision activity at abasic sites in tandem repeat sequ... | KEEP AS NON CORE | Summary: APEX1 contributes to telomere maintenance by processing AP sites in telomeric DNA. Reason: Telomere maintenance is a specialized application of APEX1's BER function. The primary function is general BER; telomere-specific activity is a secondary consequence. Supporting Evidence: PMID:24703901 APE1 incision activity at abasic sites in tandem repeat sequences |
| GO:0000781 chromosome, telomeric region | IC PMID:24703901 APE1 incision activity at abasic sites in tandem repeat sequ... | KEEP AS NON CORE | Summary: Inferred curator annotation that APEX1 localizes to telomeres based on its telomeric DNA binding and maintenance activities. Reason: Telomeric localization is inferred from functional data. This is a specialized location consistent with telomere maintenance function. Supporting Evidence: PMID:24703901 APE1 incision activity at abasic sites in tandem repeat sequences |
| GO:0003684 damaged DNA binding | IDA PMID:24703901 APE1 incision activity at abasic sites in tandem repeat sequ... | ACCEPT | Summary: APEX1 binds to damaged DNA containing abasic sites. Reason: Damaged DNA binding is essential for APEX1's recognition of repair substrates. Supporting Evidence: PMID:24703901 APE1 incision activity at abasic sites in tandem repeat sequences |
| GO:0003691 double-stranded telomeric DNA binding | IDA PMID:24703901 APE1 incision activity at abasic sites in tandem repeat sequ... | KEEP AS NON CORE | Summary: APEX1 binds to double-stranded telomeric DNA containing AP sites. Reason: Telomeric DNA binding is a specialized aspect of APEX1's damaged DNA binding function. Supporting Evidence: PMID:24703901 APE1 incision activity at abasic sites in tandem repeat sequences |
| GO:0003906 DNA-(apurinic or apyrimidinic site) endonuclease activity | IDA PMID:24703901 APE1 incision activity at abasic sites in tandem repeat sequ... | ACCEPT | Summary: AP endonuclease activity at telomeric AP sites. Reason: Core molecular function annotation. Supporting Evidence: PMID:24703901 APE1 incision activity at abasic sites in tandem repeat sequences |
| GO:0008309 double-stranded DNA exodeoxyribonuclease activity | IDA PMID:24703901 APE1 incision activity at abasic sites in tandem repeat sequ... | ACCEPT | Summary: APEX1 has exonuclease activity on double-stranded DNA substrates. Reason: Exonuclease activity is a documented enzymatic function of APEX1. Supporting Evidence: PMID:24703901 APE1 incision activity at abasic sites in tandem repeat sequences |
| GO:0003906 DNA-(apurinic or apyrimidinic site) endonuclease activity | IDA PMID:18973764 Human ribosomal protein S3 (hRpS3) interacts with uracil-DNA... | ACCEPT | Summary: Additional evidence for AP endonuclease activity. Reason: Core molecular function. Supporting Evidence: PMID:18973764 Human ribosomal protein S3 (hRpS3) interacts with uracil-DNA glycosylase (hUNG) and stimulates its glycosylase activity |
| GO:0008081 phosphoric diester hydrolase activity | IDA PMID:18973764 Human ribosomal protein S3 (hRpS3) interacts with uracil-DNA... | ACCEPT | Summary: Phosphodiester hydrolase activity of APEX1. Reason: Core enzymatic function. Supporting Evidence: PMID:18973764 Human ribosomal protein S3 (hRpS3) interacts with uracil-DNA glycosylase (hUNG) and stimulates its glycosylase activity |
| GO:0003906 DNA-(apurinic or apyrimidinic site) endonuclease activity | IDA PMID:15707971 Characterization of a wide range base-damage-endonuclease ac... | ACCEPT | Summary: Additional evidence for AP endonuclease activity. Reason: Core molecular function. Supporting Evidence: PMID:15707971 Characterization of a wide range base-damage-endonuclease activity of mammalian rpS3 |
| GO:0003684 damaged DNA binding | IDA PMID:14706345 Characterization of human ribosomal protein S3 binding to 7,... | ACCEPT | Summary: APEX1 binds to DNA containing 8-oxoguanine and abasic sites. Reason: Damaged DNA binding is essential for substrate recognition. Supporting Evidence: PMID:14706345 Characterization of human ribosomal protein S3 binding to 7,8-dihydro-8-oxoguanine and abasic sites by surface plasmon resonance |
| GO:0006287 base-excision repair, gap-filling | TAS Reactome:R-HSA-73933 | ACCEPT | Summary: APEX1 participates in BER gap-filling by coordinating with DNA polymerase beta after AP site incision. Reason: This describes APEX1's role in the downstream steps of BER where the gap is filled after AP site incision. Supporting Evidence: Reactome:R-HSA-73933 Resolution of Abasic Sites (AP sites) |
| GO:0004520 DNA endonuclease activity | TAS Reactome:R-HSA-110359 | ACCEPT | Summary: APEX1 has DNA endonuclease activity, cleaving at AP sites. Reason: DNA endonuclease activity is a core molecular function of APEX1. Supporting Evidence: Reactome:R-HSA-110359 APEX1 mediates endonucleolytic cleavage at the 5' side of the AP site |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-110349 | ACCEPT | Summary: APEX1 localizes to nucleoplasm for BER function. Reason: Nucleoplasm localization is consistent with APEX1's nuclear DNA repair function. Multiple Reactome pathways place APEX1 in the nucleoplasm. Supporting Evidence: Reactome:R-HSA-110349 Displacement of UNG glycosylase by APEX1 at the AP site |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-110350 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome TDG displacement reaction. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-110350 Displacement of TDG glycosylase by APEX1 at the AP site |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-110351 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome SMUG1 displacement reaction. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-110351 Displacement of SMUG1 glycosylase by APEX1 at the AP site |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-110352 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome NTHL1 displacement reaction. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-110352 Displacement of NTHL1 glycosylase by APEX1 at the AP site |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-110353 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome MBD4 displacement reaction. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-110353 Displacement of MBD4 glycosylase by APEX1 at the AP site |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-110354 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome OGG1 displacement reaction. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-110354 Displacement of OGG1 glycosylase by APEX1 at the AP site |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-110355 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome MUTYH displacement reaction. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-110355 Displacement of MUTYH glycosylase by APEX1 at the AP site |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-110356 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome MPG displacement reaction. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-110356 Displacement of MPG glycosylase by APEX1 at the AP site |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-110359 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome AP site cleavage reaction. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-110359 APEX1 mediates endonucleolytic cleavage at the 5' side of the AP site |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-110360 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome POLB recruitment. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-110360 Recruitment of POLB to the AP site |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-110363 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome FEN1 cleavage reaction. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-110363 FEN1 bound to PCNA and APEX1 cleaves flap ssDNA |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-110364 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome long-patch BER. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-110364 PCNA:POLD,POLE:RPA:RFC and FEN1 bind APEX1 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-110368 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome strand displacement. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-110368 POLD,POLE-mediated DNA strand displacement synthesis |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-110371 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome LIG1 binding. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-110371 LIG1 binds APEX1 and PCNA at SSB |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-110375 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome dRP excision. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-110375 Excision of the abasic sugar phosphate (5'dRP) residue at the single strand break |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-111253 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome POLB incorporation. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-111253 POLB incorporates the first 3' dNMP and displaces 5'ddRP at SSB site |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5649854 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome oxidatively damaged AP site. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-5649854 Recruitment of POLB to oxidatively damaged AP site |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5649856 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome oxidative damage. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-5649856 Oxidative damage to the AP site |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5649873 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome PARP binding. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-5649873 PARP1,PARP2 dimers and FEN1 bind POLB and displace APEX1 from damaged AP site |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5651805 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome ligation. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-5651805 LIG1 bound to APEX1 and PCNA ligates SSB |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5651809 | ACCEPT | Summary: Duplicate nucleoplasm annotation from Reactome dissociation. Reason: Consistent with other nucleoplasm localizations. Supporting Evidence: Reactome:R-HSA-5651809 LIG1, APEX1 and PCNA:POLD,POLE:RPA:RFC dissociate from repaired DNA |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | ACCEPT | Summary: High-throughput study identifying APEX1 as an mRNA-binding protein. Reason: RNA binding is documented for APEX1, particularly for its endoribonuclease function on c-myc mRNA and rRNA quality control. Supporting Evidence: PMID:22681889 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts |
| GO:0003684 damaged DNA binding | IDA PMID:12524539 Cleaving the oxidative repair protein Ape1 enhances cell dea... | ACCEPT | Summary: APEX1 binds damaged DNA as part of SET complex function. Reason: Damaged DNA binding is essential for APEX1's repair function. Supporting Evidence: PMID:12524539 Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A |
| GO:0005654 nucleoplasm | IDA PMID:17148573 UVA irradiation induces relocalisation of the DNA repair pro... | ACCEPT | Summary: IDA evidence for nucleoplasm localization. Reason: Consistent with other evidence for nucleoplasm localization. Supporting Evidence: PMID:17148573 UVA irradiation induces relocalisation of the DNA repair protein hOGG1 to nuclear speckles |
| GO:0005730 nucleolus | IDA PMID:17148573 UVA irradiation induces relocalisation of the DNA repair pro... | ACCEPT | Summary: IDA evidence for nucleolus localization. Reason: Nucleolar localization is consistent with APEX1's rRNA quality control function. Supporting Evidence: PMID:17148573 UVA irradiation induces relocalisation of the DNA repair protein hOGG1 to nuclear speckles |
| GO:0016491 oxidoreductase activity | IDA PMID:12524539 Cleaving the oxidative repair protein Ape1 enhances cell dea... | ACCEPT | Summary: APEX1 has redox/oxidoreductase activity that regulates transcription factor DNA binding. Reason: Oxidoreductase activity is a core molecular function of APEX1/Ref-1, mediating the reduction of cysteines in transcription factors. Supporting Evidence: PMID:12524539 Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A |
| GO:0016607 nuclear speck | IDA PMID:17148573 UVA irradiation induces relocalisation of the DNA repair pro... | ACCEPT | Summary: APEX1 localizes to nuclear speckles after genotoxic stress. Reason: Nuclear speck localization is documented, particularly after DNA damage. Supporting Evidence: PMID:17148573 UVA irradiation induces relocalisation of the DNA repair protein hOGG1 to nuclear speckles |
| GO:0005634 nucleus | IDA PMID:15942031 Analysis of nuclear transport signals in the human apurinic/... | ACCEPT | Summary: IDA evidence for nuclear localization with NLS characterization. Reason: This study characterized APEX1's nuclear localization signal. Supporting Evidence: PMID:15942031 Analysis of nuclear transport signals in the human apurinic/apyrimidinic endonuclease (APE1/Ref1) |
| GO:0005737 cytoplasm | IDA PMID:9560228 Activation of apurinic/apyrimidinic endonuclease in human ce... | ACCEPT | Summary: APEX1 detected in cytoplasm under certain conditions. Reason: Cytoplasmic localization occurs in response to oxidative stress and other signals. Supporting Evidence: PMID:9560228 Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species and its correlation with their adaptive response to genotoxicity of free radicals |
| GO:0006281 DNA repair | IDA PMID:9560228 Activation of apurinic/apyrimidinic endonuclease in human ce... | ACCEPT | Summary: DNA repair function of APEX1 in oxidative stress response. Reason: DNA repair is the core function of APEX1. Supporting Evidence: PMID:9560228 Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species and its correlation with their adaptive response to genotoxicity of free radicals |
| GO:0008408 3'-5' exonuclease activity | IDA PMID:11832948 An exonucleolytic activity of human apurinic/apyrimidinic en... | ACCEPT | Summary: APEX1 has 3'-5' exonuclease activity on mismatched DNA. Reason: This is a documented enzymatic activity of APEX1. Supporting Evidence: PMID:11832948 An exonucleolytic activity of human apurinic/apyrimidinic endonuclease on 3' mispaired DNA |
| GO:0043488 regulation of mRNA stability | IMP PMID:19401441 Identification of Apurinic/apyrimidinic endonuclease 1 (APE1... | ACCEPT | Summary: APEX1 regulates c-myc mRNA stability through its endoribonuclease activity. Reason: This biological process annotation reflects APEX1's endoribonuclease function in mRNA metabolism. Supporting Evidence: PMID:19401441 Identification of Apurinic/apyrimidinic endonuclease 1 (APE1) as the endoribonuclease that cleaves c-myc mRNA |
| GO:0005739 mitochondrion | IDA PMID:20231292 Identification and characterization of mitochondrial targeti... | ACCEPT | Summary: Cleaved APEX1 localizes to mitochondria. Reason: Mitochondrial localization is documented and functionally important for mtDNA repair. Supporting Evidence: PMID:20231292 Identification and characterization of mitochondrial targeting sequence of human apurinic/apyrimidinic endonuclease 1 |
| GO:0031490 chromatin DNA binding | IDA PMID:11809897 Human AP-endonuclease 1 and hnRNP-L interact with a nCaRE-li... | ACCEPT | Summary: APEX1 binds to chromatin DNA at nCaRE elements. Reason: Chromatin DNA binding is relevant to APEX1's transcriptional regulatory function. Supporting Evidence: PMID:11809897 Human AP-endonuclease 1 and hnRNP-L interact with a nCaRE-like repressor element in the AP-endonuclease 1 promoter |
| GO:0005730 nucleolus | IDA PMID:19188445 APE1/Ref-1 interacts with NPM1 within nucleoli and plays a r... | ACCEPT | Summary: APEX1 localizes to nucleolus for rRNA quality control. Reason: Nucleolar localization is well-documented and functionally important. Supporting Evidence: PMID:19188445 APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process |
| GO:0003906 DNA-(apurinic or apyrimidinic site) endonuclease activity | IDA PMID:19188445 APE1/Ref-1 interacts with NPM1 within nucleoli and plays a r... | ACCEPT | Summary: AP endonuclease activity documented in nucleolar context. Reason: Core molecular function annotation. Supporting Evidence: PMID:19188445 APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process |
| GO:0005783 endoplasmic reticulum | TAS PMID:12524539 Cleaving the oxidative repair protein Ape1 enhances cell dea... | KEEP AS NON CORE | Summary: APEX1 detected in ER by colocalization with calreticulin. Reason: ER localization is documented but represents a minor pool of APEX1. Supporting Evidence: PMID:12524539 Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A |
| GO:0005840 ribosome | TAS PMID:12524539 Cleaving the oxidative repair protein Ape1 enhances cell dea... | KEEP AS NON CORE | Summary: APEX1 detected in ribosomal fraction, possibly related to mRNA processing function. Reason: Ribosomal localization is likely related to APEX1's RNA processing function but is not a core localization. Supporting Evidence: PMID:12524539 Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A |
| GO:0016491 oxidoreductase activity | IDA PMID:9119221 Identification of redox/repair protein Ref-1 as a potent act... | ACCEPT | Summary: APEX1/Ref-1 has oxidoreductase activity that activates p53. Reason: Oxidoreductase (redox) activity is a core function of APEX1. Supporting Evidence: PMID:9119221 Identification of redox/repair protein Ref-1 as a potent activator of p53 |
| GO:0003677 DNA binding | IDA PMID:11286553 Two divalent metal ions in the active site of a new crystal ... | ACCEPT | Summary: APEX1 binds DNA as part of its catalytic mechanism. Reason: DNA binding is essential for APEX1's enzymatic function. Supporting Evidence: PMID:11286553 Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1 |
| GO:0003713 transcription coactivator activity | IDA PMID:9119221 Identification of redox/repair protein Ref-1 as a potent act... | ACCEPT | Summary: APEX1 acts as transcription coactivator through redox regulation of p53. Reason: Transcription coactivator activity is a core function of APEX1/Ref-1. Supporting Evidence: PMID:9119221 Identification of redox/repair protein Ref-1 as a potent activator of p53 |
| GO:0003906 DNA-(apurinic or apyrimidinic site) endonuclease activity | TAS PMID:9119221 Identification of redox/repair protein Ref-1 as a potent act... | ACCEPT | Summary: Core AP endonuclease activity of APEX1. Reason: Core molecular function annotation. Supporting Evidence: PMID:9119221 Identification of redox/repair protein Ref-1 as a potent activator of p53 |
| GO:0004523 RNA-DNA hybrid ribonuclease activity | TAS PMID:11286553 Two divalent metal ions in the active site of a new crystal ... | ACCEPT | Summary: APEX1 can incise at AP sites in DNA strand of RNA-DNA hybrids. Reason: This activity is documented for APEX1 and represents substrate specificity for RNA-DNA hybrids containing AP sites. Supporting Evidence: PMID:11286553 Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1 |
| GO:0004528 phosphodiesterase I activity | TAS PMID:9119221 Identification of redox/repair protein Ref-1 as a potent act... | ACCEPT | Summary: APEX1 has 3'-phosphodiesterase activity. Reason: Phosphodiesterase activity is a documented function of APEX1. Supporting Evidence: PMID:9119221 Identification of redox/repair protein Ref-1 as a potent activator of p53 |
| GO:0005634 nucleus | IDA PMID:9119221 Identification of redox/repair protein Ref-1 as a potent act... | ACCEPT | Summary: IDA evidence for nuclear localization. Reason: Nuclear localization is well-established. Supporting Evidence: PMID:9119221 Identification of redox/repair protein Ref-1 as a potent activator of p53 |
| GO:0008408 3'-5' exonuclease activity | TAS PMID:11286553 Two divalent metal ions in the active site of a new crystal ... | ACCEPT | Summary: APEX1 has 3'-5' exonuclease activity. Reason: This enzymatic activity is documented for APEX1. Supporting Evidence: PMID:11286553 Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1 |
| GO:0046872 metal ion binding | IDA PMID:11286553 Two divalent metal ions in the active site of a new crystal ... | ACCEPT | Summary: APEX1 requires divalent metal ions (Mg2+, Mn2+) for catalysis. Reason: Metal ion binding is essential for APEX1's catalytic mechanism. Supporting Evidence: PMID:11286553 Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic mechanism |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:12524539 Cleaving the oxidative repair protein Ape1 enhances cell dea... | KEEP AS NON CORE | Summary: APEX1 detected in perinuclear region. Reason: Perinuclear localization represents cytoplasmic APEX1 pool, which is a minor fraction. Supporting Evidence: PMID:12524539 Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A |
| GO:0003714 transcription corepressor activity | TAS PMID:7961715 A redox factor protein, ref1, is involved in negative gene r... | KEEP AS NON CORE | Summary: APEX1 acts as transcription corepressor at nCaRE elements. Reason: Transcription corepressor activity is a secondary function of APEX1, distinct from its DNA repair and redox coactivator functions. Supporting Evidence: PMID:7961715 A redox factor protein, ref1, is involved in negative gene regulation by extracellular calcium |
| GO:0004520 DNA endonuclease activity | TAS PMID:1722334 Cloning and expression of APE, the cDNA encoding the major h... | ACCEPT | Summary: Core DNA endonuclease activity of APEX1. Reason: DNA endonuclease activity is a core molecular function. Supporting Evidence: PMID:1722334 Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: definition of a family of DNA repair enzymes |
| GO:0004844 uracil DNA N-glycosylase activity | TAS PMID:10805771 Uracil-DNA glycosylase-DNA substrate and product structures:... | REMOVE | Summary: This annotation appears to be incorrect. APEX1 is an AP endonuclease that acts DOWNSTREAM of uracil DNA glycosylase (UNG), not as a glycosylase itself. The cited paper is about UNG, not APEX1. Reason: APEX1 does not have uracil DNA N-glycosylase activity. It is an AP endonuclease that processes the abasic sites created by glycosylases like UNG. This appears to be an annotation error where APEX1 was confused with UNG based on their sequential roles in BER. Supporting Evidence: PMID:10805771 Uracil-DNA glycosylase-DNA substrate and product structures [this paper is about UNG, not APEX1] |
| GO:0004519 endonuclease activity | IDA PMID:11478795 Sequence analysis identifies TTRAP, a protein that associate... | ACCEPT | Summary: APEX1 has endonuclease activity. Reason: Endonuclease activity is a core molecular function of APEX1. Supporting Evidence: PMID:11478795 Sequence analysis identifies TTRAP, a protein that associates with CD40 and TNF receptor-associated factors, as a member of a superfamily of divalent cation-dependent phosphodiesterases |
| GO:0008081 phosphoric diester hydrolase activity | IDA PMID:11478795 Sequence analysis identifies TTRAP, a protein that associate... | ACCEPT | Summary: APEX1 has phosphoric diester hydrolase activity. Reason: Core enzymatic activity of APEX1. Supporting Evidence: PMID:11478795 Sequence analysis identifies TTRAP, a protein that associates with CD40 and TNF receptor-associated factors, as a member of a superfamily of divalent cation-dependent phosphodiesterases |
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Download this section (compressed HTML)Experiment: Verify the incorrect GO:0033892 (pyrimidine dimer nuclease) and GO:0004844 (uracil DNA glycosylase) annotations by testing whether APEX1 has activity on UV-induced pyrimidine dimers or can remove uracil from DNA. These activities are not consistent with APEX1's known biochemistry as an AP endonuclease.
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