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DNA-(apurinic or apyrimidinic site) lyase 2; AP endonuclease XTH2; APEX nuclease 2; APEX nuclease-like 2; apurinic-apyrimidinic endonuclease 2; AP endonuclease 2 (APEX2, APE2, APEXL2, XTH2)
Function:
- nuclear & mitochondrial post-replication base excision repair
- weak apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair pathway of DNA lesions induced by oxidative & alkylating agents
- initiates repair of apurinic/apyrimidinic 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 & 3'-hydroxyl ends.
- displays also double-stranded DNA 3'-5' exonuclease, 3'-phosphodiesterase activities
- robust 3'-5' exonuclease activity on 3'-recessed heteroduplex DNA & is able to remove mismatched nucleotides preferentially
- shows fairly strong 3'-phosphodiesterase activity involved in the removal of 3'-damaged termini formed in DNA by oxidative agents
- in the nucleus functions in the PCNA-dependent DNA base excision repair pathway
- required for somatic hypermutation & DNA cleavage step of class switch recombination of immunoglobulin genes
- required for proper cell cycle progression during proliferation of peripheral lymphocytes
- 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 & a product with a terminal 5'-phosphate
- 3'-5' exonuclease activity is activated by Na+ & Mn+2
- 3'-5' exonuclease & 3'-phosphodiesterase activities are stimulated in presence of PCNA
- interacts with PCNA; interaction is triggered by reactive oxygen species & increased by misincorporation of uracil in nuclear DNA
Kinetic parameters:
- pH dependence: optimum pH is 6.0-8.0
Structure: belongs to the DNA repair enzymes AP/exoA family
Compartment:
- nuclear, probably mitochondrial
- colocalizes partly with PCNA
Expression:
- highly expressed in cells, adult brain, kidney
- weakly expressed in the fetal brain
General
lyase
mitochondrial protein
nuclear protein
Properties
SIZE: entity length = 518 aa
MW = 57 kD
COMPARTMENT: mitochondria
cytoplasm
cell nucleus
MOTIF: manganese [Mn]-binding site
SITE: 8-8
manganese [Mn]-binding site
SITE: 48-48
manganese [Mn]-binding site
SITE: 197-197
manganese [Mn]-binding site
SITE: 199-199
manganese [Mn]-binding site
SITE: 303-303
histidine residue {H304}
manganese [Mn]-binding site
SITE: 304-304
PCNA interaction {390-397}
Database Correlations
OMIM 300773
UniProt Q9UBZ4
PFAM correlations
Entrez Gene 27301
Kegg hsa:27301
ENZYME 4.2.99.18
References
- UniProt :accession Q9UBZ4
- NIEHS-SNPs
http://egp.gs.washington.edu/data/apex2/