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Names & Taxonomy

Uniprot ID:: P27695
Entry Name:: APEX1_HUMAN
Status:: reviewed
Protein Names:: DNA-(apurinic or apyrimidinic site) lyase (EC 3.1.-.-) (EC 4.2.99.18) (APEX nuclease) (APEN) (Apurinic-apyrimidinic endonuclease 1) (AP endonuclease 1) (APE-1) (REF-1) (Redox factor-1) [Cleaved into: DNA-(apurinic or apyrimidinic site) lyase, mitochondrial]
Gene Names:: APEX1 APE APE1 APEX APX HAP1 REF1
Gene Names Primary:: APEX1
Organism:: Homo sapiens (Human)

Structure

Length:: 318
Sequence:: MPKRGKKGAVAEDGDELRTEPEAKKSKTAAKKNDKEAAGEGPALYEDPPDQKTSPSGKPATLKICSWNVDGLRAWIKKKGLDWVKEEAPDILCLQETKCSENKLPAELQELPGLSHQYWSAPSDKEGYSGVGLLSRQCPLKVSYGIGDEEHDQEGRVIVAEFDSFVLVTAYVPNAGRGLVRLEYRQRWDEAFRKFLKGLASRKPLVLCGDLNVAHEEIDLRNPKGNKKNAGFTPQERQGFGELLQAVPLADSFRHLYPNTPYAYTFWTYMMNARSKNVGWRLDYFLLSHSLLPALCDSKIRSKALGSDHCPITLYLAL
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Nucleus. Nucleus, nucleolus. Nucleus speckle. Endoplasmic reticulum. Cytoplasm. Note=Detected in the cytoplasm of B-cells stimulated to switch (By similarity). 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.

Function

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.
Catalytic Activity:: The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate.
Cofactor:: COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Enzyme Regulation:: ENZYME REGULATION: NPM1 stimulates endodeoxyribonuclease activity on double-stranded DNA with AP sites, but inhibits endoribonuclease activity on single-stranded RNA containing AP sites.
Active Site:: ACT_SITE 171 171; ACT_SITE 210 210 Proton donor/acceptor.
Cross Reference Drug Bank:: DB04967
Gene Ontology Go:: centrosome
cytoplasm
endoplasmic reticulum
mitochondrion
nuclear chromosome, telomeric region
nuclear speck
nucleolus
nucleoplasm
nucleus
perinuclear region of cytoplasm
ribosome
transcription factor complex
3'-5' exonuclease activity
chromatin DNA binding
damaged DNA binding
DNA binding
DNA-(apurinic or apyrimidinic site) lyase activity
double-stranded DNA 3'-5' exodeoxyribonuclease activity
double-stranded DNA exodeoxyribonuclease activity
double-stranded telomeric DNA binding
endodeoxyribonuclease activity
endonuclease activity
metal ion binding
oxidoreductase activity
phosphodiesterase I activity
phosphoric diester hydrolase activity
poly(A) RNA binding
RNA-DNA hybrid ribonuclease activity
site-specific endodeoxyribonuclease activity, specific for altered base
transcription coactivator activity
transcription corepressor activity
uracil DNA N-glycosylase activity
aging
base-excision repair
cell redox homeostasis
cellular response to cAMP
cellular response to hydrogen peroxide
cellular response to peptide hormone stimulus
DNA demethylation
DNA repair
DNA strand elongation involved in DNA replication
mitotic cell cycle
negative regulation of nucleic acid-templated transcription
negative regulation of smooth muscle cell migration
oxidation-reduction process
positive regulation of DNA repair
positive regulation of G1/S transition of mitotic cell cycle
regulation of mRNA stability
regulation of transcription, DNA-templated
response to drug
telomere maintenance
telomere maintenance via recombination
telomere maintenance via semi-conservative replication
transcription, DNA-templated
Gene Ontology Biological Process:: aging
base-excision repair
cell redox homeostasis
cellular response to cAMP
cellular response to hydrogen peroxide
cellular response to peptide hormone stimulus
DNA demethylation
DNA repair
DNA strand elongation involved in DNA replication
mitotic cell cycle
negative regulation of nucleic acid-templated transcription
negative regulation of smooth muscle cell migration
oxidation-reduction process
positive regulation of DNA repair
positive regulation of G1/S transition of mitotic cell cycle
regulation of mRNA stability
regulation of transcription, DNA-templated
response to drug
telomere maintenance
telomere maintenance via recombination
telomere maintenance via semi-conservative replication
transcription, DNA-templated
Gene Ontology Molecular Function:: 3'-5' exonuclease activity
chromatin DNA binding
damaged DNA binding
DNA-(apurinic or apyrimidinic site) lyase activity
DNA binding
double-stranded DNA 3'-5' exodeoxyribonuclease activity
double-stranded DNA exodeoxyribonuclease activity
double-stranded telomeric DNA binding
endodeoxyribonuclease activity
endonuclease activity
metal ion binding
oxidoreductase activity
phosphodiesterase I activity
phosphoric diester hydrolase activity
poly(A) RNA binding
RNA-DNA hybrid ribonuclease activity
site-specific endodeoxyribonuclease activity, specific for altered base
transcription coactivator activity
transcription corepressor activity
uracil DNA N-glycosylase activity
Gene Ontology Cellular Component:: centrosome
cytoplasm
endoplasmic reticulum
mitochondrion
nuclear chromosome, telomeric region
nuclear speck
nucleolus
nucleoplasm
nucleus
perinuclear region of cytoplasm
ribosome
transcription factor complex
Keywords:: 3D-structure
Acetylation
Activator
Cleavage on pair of basic residues
Complete proteome
Cytoplasm
DNA damage
DNA recombination
DNA repair
DNA-binding
Direct protein sequencing
Disulfide bond
Endonuclease
Endoplasmic reticulum
Exonuclease
Hydrolase
Lyase
Magnesium
Metal-binding
Mitochondrion
Nuclease
Nucleus
Phosphoprotein
Polymorphism
RNA-binding
Reference proteome
Repressor
S-nitrosylation
Transcription
Transcription regulation
Ubl conjugation
Interacts With:: Q09472; Q96EB6

Names & Taxonomy

Structure

Subcellular location

Function

Publication