Version 5.4
Bos taurus Protein: APEX1
Summary
InnateDB Protein IDBP-698822.3
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol APEX1
Protein Name DNA-(apurinic or apyrimidinic site) lyase
Synonyms APEN; BAP1; REF-1;
Species Bos taurus
Ensembl Protein ENSBTAP00000003559
InnateDB Gene IDBG-646052 (APEX1)
Protein Structure
UniProt Annotation
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 in 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 (By similarity). {ECO:0000250}.
Subcellular Localization Nucleus {ECO:0000255PROSITE- ProRule:PRU00764, ECO:0000269PubMed:16617147}. Nucleus, nucleolus {ECO:0000250}. Nucleus speckle {ECO:0000255PROSITE- ProRule:PRU00764}. Endoplasmic reticulum {ECO:0000250}. Cytoplasm {ECO:0000255PROSITE-ProRule:PRU00764}. Note=Detected in the cytoplasm of B-cells stimulated to switch. Colocalized with SIRT1 in the nucleus. Colocalized with YBX1 in nuclear speckles after genotoxic stress. Together with OGG1 is recruited to nuclear speckles in UVA-irradiated cells. Colocalized with nucleolin and NPM1 in the nucleolus. Its nucleolar localization is cell cycle dependent and requires active rRNA transcription. Colocalized with calreticulin in the endoplasmic reticulum. Translocation from the nucleus to the cytoplasm is stimulated in presence of nitric oxide (NO) and function in a CRM1-dependent manner, possibly as a consequence of demasking a nuclear export signal (amino acid position 64-80). S-nitrosylation at Cys-93 and Cys-310 regulates its nuclear-cytosolic shuttling. Ubiquitinated form is localized predominantly in the cytoplasm.DNA-(apurinic or apyrimidinic site) lyase, mitochondrial: Mitochondrion. Note=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 (By similarity). The cleaved APEX2 is only detected in mitochondria. {ECO:0000250}.
Disease Associations
Tissue Specificity The mitochondrial form is expressed in liver (at protein level). Thymus. {ECO:0000269PubMed:16617147}.
Comments
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 0 experimentally validated interaction(s) in this database.
They are also associated with 50 interaction(s) predicted by orthology.
Predicted by orthology
Total 50 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0003677 DNA binding
GO:0003684 damaged DNA binding
GO:0003713 transcription coactivator activity
GO:0003723 RNA binding
GO:0003906 DNA-(apurinic or apyrimidinic site) lyase activity
GO:0004518 nuclease activity
GO:0004519 endonuclease activity
GO:0004527 exonuclease activity
GO:0005515 protein binding
GO:0008081 phosphoric diester hydrolase activity
GO:0008311 double-stranded DNA 3'-5' exodeoxyribonuclease activity
GO:0008408 3'-5' exonuclease activity
GO:0016491 oxidoreductase activity
GO:0016787 hydrolase activity
GO:0016829 lyase activity
GO:0016890 site-specific endodeoxyribonuclease activity, specific for altered base
GO:0031490 chromatin DNA binding
GO:0044822 poly(A) RNA binding
GO:0046872 metal ion binding
Biological Process
GO:0000737 DNA catabolic process, endonucleolytic
GO:0000738 DNA catabolic process, exonucleolytic
GO:0006281 DNA repair
GO:0006284 base-excision repair
GO:0006310 DNA recombination
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006974 cellular response to DNA damage stimulus
GO:0043488 regulation of mRNA stability
GO:0045454 cell redox homeostasis
GO:0045739 positive regulation of DNA repair
GO:0055114 oxidation-reduction process
GO:0080111 DNA demethylation
GO:0090305 nucleic acid phosphodiester bond hydrolysis
Cellular Component
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005783 endoplasmic reticulum
GO:0005813 centrosome
GO:0016607 nuclear speck
GO:0048471 perinuclear region of cytoplasm
Protein Structure and Domains
PDB ID
InterPro IPR004808 AP endonuclease 1
IPR005135 Endonuclease/exonuclease/phosphatase
PFAM PF03372
PF14529
PRINTS
PIRSF
SMART
TIGRFAMs
Post-translational Modifications
Modification
Cross-References
SwissProt P23196
PhosphoSite PhosphoSite-
TrEMBL
UniProt Splice Variant
Entrez Gene 281630
UniGene Bt.1302
RefSeq NP_788782
HUGO
OMIM
CCDS
HPRD
IMGT
EMBL BC122610 X56685
GenPept AAI22611 CAA40014

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

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Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca