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MT000969

UniProt Annotations

Entry Information

Gene Name	APEX nuclease (apurinic/apyrimidinic endonuclease) 2
Protein Entry	APEX2_HUMAN
UniProt ID	Q9UBZ4
Species	Human

Comments

Comment type	Description
Biophysicochemical Properties	pH dependence: Optimum pH is 6.0-8.0. {ECO:0000269\|PubMed:16687656};
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. {ECO:0000255\|PROSITE-ProRule:PRU00764}.
Cofactor	Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250}; Note=Probably binds two magnesium or manganese ions per subunit. {ECO:0000250};
Enzyme Regulation	3'-5' exonuclease activity is activated by sodium and manganese. 3'-5' exonuclease and 3'-phosphodiesterase activities are stimulated in presence of PCNA.
Function	Function as a weak 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. Displays also double-stranded DNA 3'-5' exonuclease, 3'-phosphodiesterase activities. Shows robust 3'-5' exonuclease activity on 3'-recessed heteroduplex DNA and 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 BER pathway. Required for somatic hypermutation (SHM) and DNA cleavage step of class switch recombination (CSR) of immunoglobulin genes. Required for proper cell cycle progression during proliferation of peripheral lymphocytes. {ECO:0000269\|PubMed:11376153, ECO:0000269\|PubMed:16687656, ECO:0000269\|PubMed:19443450}.
Similarity	Belongs to the DNA repair enzymes AP/ExoA family. {ECO:0000305}.
Subcellular Location	Nucleus. Cytoplasm. Mitochondrion {ECO:0000305}. Note=Together with PCNA, is redistributed in discrete nuclear foci in presence of oxidative DNA damaging agents.
Subunit	Interacts with PCNA; this interaction is triggered by reactive oxygen species and increased by misincorporation of uracil in nuclear DNA. {ECO:0000269\|PubMed:11376153}.
Tissue Specificity	Highly expressed in brain and kidney. Weakly expressed in the fetal brain. {ECO:0000269\|PubMed:11376153}.
Web Resource	Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/apex2/";