InnateDB Protein
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IDBP-698822.3
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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APEX1
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Protein Name
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DNA-(apurinic or apyrimidinic site) lyase
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Synonyms
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APEN; BAP1; REF-1;
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Species
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Bos taurus
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Ensembl Protein
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ENSBTAP00000003559
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InnateDB Gene
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IDBG-646052 (APEX1)
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Protein Structure
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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}.
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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}.
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Disease Associations |
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Tissue Specificity |
The mitochondrial form is expressed in liver (at protein level). Thymus. {ECO:0000269PubMed:16617147}.
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Comments |
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Number of Interactions
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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.
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Predicted by orthology |
Total |
50 [view]
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Molecular Function |
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Biological Process |
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Cellular Component |
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PDB ID |
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InterPro |
IPR004808
AP endonuclease 1
IPR005135
Endonuclease/exonuclease/phosphatase
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PFAM |
PF03372
PF14529
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PRINTS |
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PIRSF |
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SMART |
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TIGRFAMs |
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Modification |
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SwissProt |
P23196
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PhosphoSite |
PhosphoSite-
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TrEMBL |
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UniProt Splice Variant |
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Entrez Gene |
281630
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UniGene |
Bt.1302
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RefSeq |
NP_788782
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HUGO |
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OMIM |
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CCDS |
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HPRD |
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IMGT |
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EMBL |
BC122610
X56685
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GenPept |
AAI22611
CAA40014
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