Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol APEX1 contributors: mct/pgu - updated : 06-04-2013
HGNC name APEX nuclease (multifunctional DNA repair enzyme) 1
HGNC id 587
Location 14q11.2      Physical location : 20.923.289 - 20.925.925
Synonym name
  • apurinic endonuclease
  • abasic sites (apurinic/apyrimidic) reparing endonuclease
  • apurinic/apyrimidinic (abasic) endonuclease
  • deoxyribonuclease (apurinic or apyrimidinic)
  • apurinic-apyrimidinic endonuclease 1
  • apurinic/apyrimidinic exonuclease
  • redox factor 1
  • multifunctional DNA repair enzyme
  • Synonym symbol(s) APE, HAP1, APE1, REF1, APX, APEN, APEN, REF-1, APE-1
    EC.number 4.2.99.18
    DNA
    TYPE functioning gene
    SPECIAL FEATURE arranged in tandem
    STRUCTURE 2.64 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (CAAT box)
    MAPPING cloned Y linked N status confirmed
    Map cen - D14S780 - D14S261 - APEX1 - D14S72 - D14S1043 - qter
    Physical map
    LOC390432 14 similar to olfactory receptor MOR239-6 LOC122740 14q11.2 similar to Olfactory receptor 4K14 LOC390433 14 similar to Olfactory receptor 4K13 LOC390434 14 similar to Olfactory receptor 4K2 LOC122742 14q11.2 similar to Olfactory receptor 4L1 LOC390435 14 similar to Olfactory receptor 4K13 LOC390436 14 similar to Olfactory receptor 4K17 LOC390437 14 similar to Olfactory receptor 4N5 LOC390438 14 similar to Olfactory receptor 11G2 LOC390439 14 similar to Olfactory receptor 11G2 LOC390440 14 similar to Olfactory receptor 11H6 LOC122748 14q11.2 similar to Olfactory receptor 11H6 LOC390441 14 similar to olfactory receptor LOC390442 14 similar to Olfactory receptor 11H4 TTC5 14q11.2 tetratricopeptide repeat domain 5 C14orf18 14q11.2 chromosome 14 open reading frame 18 ADPRTL2 14q11.2 ADP-ribosyltransferase (NAD+; poly(ADP-ribose) polymerase)-like 2 TEP1 14q11.2 telomerase-associated protein 1 LOC123103 14q11.2 similar to kelch-like 4 isoform 2 OSGEP 14q11.1 O-sialoglycoprotein endopeptidase APEX1 14q11.2-q12 APEX nuclease (multifunctional DNA repair enzyme) 1 C14orf9 14q11.1 chromosome 14 open reading frame 9 NP 14q13.1 nucleoside phosphorylase LOC338879 14q11.2 similar to putative pancreatic ribonuclease LOC390443 14 similar to Ribonuclease-like protein 9 precursor C14orf6 14q11.1 chromosome 14 open reading frame 6 LOC254028 14q11.2 hypothetical protein LOC254028 LOC341799 14q11.2 similar to Olfactory receptor 6S1 RNASE4 14q11.2 ribonuclease, RNase A family, 4 ANG 14q11.2 angiogenin, ribonuclease, RNase A family, 5 RANBP20P 14 RAN binding protein 20 pseudogene FAM12A 14q11.1 family with sequence similarity 12, member A FAM12B 14q11.1 family with sequence similarity 12, member B (epididymal) RNASE6 14q11.2 ribonuclease, RNase A family, k6 RNASE1 14q11 ribonuclease, RNase A family, 1 (pancreatic) RNASE3 14q11.2 ribonuclease, RNase A family, 3 (eosinophil cationic protein)
    RNA
    TRANSCRIPTS type messenger
    text All variants encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 1574 35.4 318 - 2005 16199212
    5 splicing 1511 35.4 318 - 2005 16199212
    5 splicing 1501 35.4 318 - 2005 16199212
    5 - 1558 - 318 - 2005 16199212
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
    Reproductivefemale systemuteruscervix highly
    Skin/Tegumentskin   highly
    Visualeyeretina  highly Mus musculusAdult
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • the nuclear localization signal (NLS) sequence is devoted to redox activity
  • APE1 N terminus is essential for binding to a number of proteins involved in ribosome biogenesis and RNA processing
  • C-terminal exerts enzymatic activity on the abasic sites of DNA
  • a mitochondrial targeting sequence
  • has a unique cysteine residue C65, which maintains the reduce state of several transcriptional activators such as NFKB1
  • mono polymer monomer
    HOMOLOGY
    interspecies ortholog to Apex1, Mus musculus
    ortholog to Xth (exonuclease III), Escherichia coli
    ortholog to APEX1, Rattus norvegicus
    Homologene
    FAMILY
  • DNA repair enzymes AP/exoA family
  • CATEGORY enzyme , regulatory , DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,ribosome
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    intracellular,nucleus,nucleolus
    text
  • APEX1 subcellular distribution is mainly nuclear
  • Cytoplasmic, mitochondrial and endoplasmic reticulum
  • localization has also been reported
  • Cys-65 controls APEX1 subcellular trafficking
  • nucleolar accumulation of APEX1 depends on charged lysine residues that undergo acetylation upon genotoxic stress and modulate its BER activity in cells
  • basic FUNCTION
  • APEX nuclease (multifunctional DNA repair enzyme), endonuclease, apurinic
  • cleavage of phosphodiester bond immediately 5' to apurinic sites
  • is a redox coactivator of different transcription factors, such as early growth response protein 1 (Egr-1), NF-kB and p53
  • APEX1 is essential for early embryonic development in mice
  • may be involved in reducing the cytotoxicity and improving the therapeutic index of anti-HIV compounds belonging to the chain terminator category
  • playing an essential role for coping with the endogenous DNA damage in human cells grown in culture
  • repairs oxidative DNA damages in vitro
  • may have a role in protection against cell lethality and suppression of mutations
  • affects cell growth by directly acting on RNA quality control mechanisms
  • is a vital protein that acts as a master regulator of cellular response to oxidative stress conditions and contributes to the maintenance of genome stability
  • NPM1-APE1 interaction is required for APE1 subnuclear localization and for modulating the cleansing process of rRNA
  • playing a central role in the cellular response to oxidative stress
  • not only involved in base excision repair, but also activates some transcriptional factors through its redox activity
  • key enzyme in the DNA base excision repair (BER) pathway
  • APEX1 redox function is required for retinal angiogenesis
  • major mammalian enzyme in DNA base excision repair that cleaves the DNA phosphodiester backbone immediately 5prime to abasic sites
  • protects cells from oxidative stress via the base excision repair pathway and as a redox transcriptional coactivator
  • upstream effector of VEGF, as well as other molecules that relate to angiogenesis and the tumor microenvironment, it is also being studied as a possible treatment for agerelated macular degeneration and diabetic retinopathy
  • unique redox factor with properties distinct from those of other redox factors
  • multifunctional protein critical for cellular survival
  • in neurons, nuclear compartmentalization of APEX1 depends on ATP and loss of nuclear APEX1 reflects disruption of neuronal energy homeostasis
  • main abasic endonuclease in the base excision repair (BER) pathway of DNA lesions caused by oxidation/alkylation in mammalian cells
  • major apurinic/apyrimidinic (AP) endonuclease that initiates the processing of AP sites
  • key role in telomere maintenance
  • multifunctional protein operating in protection of cells from oxidative stress via its DNA repair, redox, and transcription regulatory activities
  • functions in DNA repair of telomeres during the synthesis of DNA
  • is an essential DNA repair protein that also possesses the ability to regulate transcription
  • CELLULAR PROCESS cell life, proliferation/growth
    nucleotide, repair, base excision repair
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    text apurinic/apyrimidinic (AP) endonuclease, 3-prime,5-prime-exonuclease, DNA 3-prime repair diesterase and DNA 3-prime-phosphatase activities
    PATHWAY
    metabolism
    signaling
    removes the blocking groups from the 3'-termini of the DNA strand breaks generated by ionizing radiations and bleomycin
    a component
    INTERACTION
    DNA binds to the negative calcium response elements (nCaRE) of some promoters (PTH and APE1)
    RNA 47S, 28S and 18S rRNA
    small molecule metal binding,
  • Mg2+
  • protein
  • XRCC1 (stimulation)
  • stimulating both FEN1 and LIG1 in long patch BER
  • interaction with APTX, PARP1 (synergistic functions of aprataxin, PARP1 and APEX1 in the cellular response to DNA damage and the modulating function of aprataxin on base excision and long patch repair)
  • target of SIRT1 protein deacetylase (SIRT1 associates with APEX1, and this association is increased with genotoxic stress)
  • cytoplasmic APEX1, but not nuclear APEX1, induced PTGS2 expression through NF-kappaB activation
  • stably interacts with Y-box-binding protein 1 (YBX1), and acts as its coactivator for the expression of multidrug resistance gene ABCB1, thereby causing drug resistance
  • transcriptional repressor of CYP11B2 and differential APEX1 binding at -1651 of CYP11B2 results in altered gene expression
  • associates with TERF2 and POT1 in the cell
  • APEX1 interacts with a novel partner PRDX1, a peroxidase that can also prevent oxidative damage to proteins by serving as a chaperone
  • cell & other
    REGULATION
    activated by XRCC1 for the base exision repair
    nucleophosmin (NPM1) stimulates APE1 endonuclease activity on abasic DNA
    inhibited by NPM1 inhibits APE1 endonuclease activity on RNA
    Other stimulated by heat shock protein 70 (HSPAX)
    deacetylated by SIRT1
    emerging role of acetylation of critical Lys residues in regulating APEX1 functions
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in human pancreatic cancer cells
    constitutional     --low  
    its depletion causes chromosome segregation defects and telomere dysfunction
    Susceptibility susceptibility gene for SLA
    Variant & Polymorphism
    Candidate gene
    Marker
  • polymorphism in the gene APEX1 may be indicated as a potential marker for prostate cancer risk
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivepancreas
    E3330, inhibitor of APEX1 has therapeutic potential in pancreatic cancer
    neurosensorialvisualdegenerative
    may have potential as a therapeutic target for treating neovascular age-related macular degeneration and other neovascular diseases
    ANIMAL & CELL MODELS
  • Ref1 -/- mice died during embryonic development following blastocyst formation after implantation
  • APE1+/- mice are Ape haploinsufficient with a 40 to 50% reduction in Ape mRNA, protein, and 5-prime endonuclease activity in liver, brain and testis