DNA-(apurinic or apyrimidinic site) lyase

Details

Name
DNA-(apurinic or apyrimidinic site) lyase
Synonyms
  • 3.1.-.-
  • AP endonuclease 1
  • APE
  • APE-1
  • APE1
  • APEN
  • APEX
  • APEX nuclease
  • Apurinic-apyrimidinic endonuclease 1
  • APX
  • HAP1
  • Redox factor-1
  • REF-1
  • REF1
Gene Name
APEX1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0011727|DNA-(apurinic or apyrimidinic site) lyase
MPKRGKKGAVAEDGDELRTEPEAKKSKTAAKKNDKEAAGEGPALYEDPPDQKTSPSGKPA
TLKICSWNVDGLRAWIKKKGLDWVKEEAPDILCLQETKCSENKLPAELQELPGLSHQYWS
APSDKEGYSGVGLLSRQCPLKVSYGIGDEEHDQEGRVIVAEFDSFVLVTAYVPNAGRGLV
RLEYRQRWDEAFRKFLKGLASRKPLVLCGDLNVAHEEIDLRNPKGNKKNAGFTPQERQGF
GELLQAVPLADSFRHLYPNTPYAYTFWTYMMNARSKNVGWRLDYFLLSHSLLPALCDSKI
RSKALGSDHCPITLYLAL
Number of residues
318
Molecular Weight
35554.165
Theoretical pI
8.26
GO Classification
Functions
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 / 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
Processes
base-excision repair / cell redox homeostasis / DNA demethylation / DNA repair / DNA strand elongation involved in DNA replication / mitotic cell cycle / negative regulation of nucleic acid-templated transcription / nucleic acid phosphodiester bond hydrolysis / oxidation-reduction process / positive regulation of DNA repair / regulation of mRNA stability / regulation of transcription, DNA-templated / RNA phosphodiester bond hydrolysis, endonucleolytic / telomere maintenance / telomere maintenance via recombination / telomere maintenance via semi-conservative replication / transcription, DNA-templated
Components
centrosome / cytoplasm / endoplasmic reticulum / mitochondrion / nuclear speck / nucleolus / nucleoplasm / nucleus / perinuclear region of cytoplasm / ribosome
General Function
Uracil dna n-glycosylase activity
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0011728|DNA-(apurinic or apyrimidinic site) lyase (APEX1)
ATGCCGAAGCGTGGGAAAAAGGGAGCGGTGGCGGAAGACGGGGATGAGCTCAGGACAGAG
CCAGAGGCCAAGAAGAGTAAGACGGCCGCAAAGAAAAATGACAAAGAGGCAGCAGGAGAG
GGCCCAGCCCTGTATGAGGACCCCCCAGATCAGAAAACCTCACCCAGTGGCAAACCTGCC
ACACTCAAGATCTGCTCTTGGAATGTGGATGGGCTTCGAGCCTGGATTAAGAAGAAAGGA
TTAGATTGGGTAAAGGAAGAAGCCCCAGATATACTGTGCCTTCAAGAGACCAAATGTTCA
GAGAACAAACTACCAGCTGAACTTCAGGAGCTGCCTGGACTCTCTCATCAATACTGGTCA
GCTCCTTCGGACAAGGAAGGGTACAGTGGCGTGGGCCTGCTTTCCCGCCAGTGCCCACTC
AAAGTTTCTTACGGCATAGGCGATGAGGAGCATGATCAGGAAGGCCGGGTGATTGTGGCT
GAATTTGACTCGTTTGTGCTGGTAACAGCATATGTACCTAATGCAGGCCGAGGTCTGGTA
CGACTGGAGTACCGGCAGCGCTGGGATGAAGCCTTTCGCAAGTTCCTGAAGGGCCTGGCT
TCCCGAAAGCCCCTTGTGCTGTGTGGAGACCTCAATGTGGCACATGAAGAAATTGACCTT
CGCAACCCCAAGGGGAACAAAAAGAATGCTGGCTTCACGCCACAAGAGCGCCAAGGCTTC
GGGGAATTACTGCAGGCTGTGCCACTGGCTGACAGCTTTAGGCACCTCTACCCCAACACA
CCCTATGCCTACACCTTTTGGACTTATATGATGAATGCTCGATCCAAGAATGTTGGTTGG
CGCCTTGATTACTTTTTGTTGTCCCACTCTCTGTTACCTGCATTGTGTGACAGCAAGATC
CGTTCCAAGGCCCTCGGCAGTGATCACTGTCCTATCACCCTATACCTAGCACTGTGA
Chromosome Location
14
Locus
14q11.2-q12
External Identifiers
ResourceLink
UniProtKB IDP27695
UniProtKB Entry NameAPEX1_HUMAN
GenBank Gene IDX66133
GenAtlas IDAPEX1
HGNC IDHGNC:587
General References
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  2. Demple B, Herman T, Chen DS: Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: definition of a family of DNA repair enzymes. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11450-4. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB04967LucanthoneinvestigationalyesinhibitorDetails