Q9UBZ4 · APEX2_HUMAN
- ProteinDNA-(apurinic or apyrimidinic site) endonuclease 2
- GeneAPEX2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids518 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Functions as a weak apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents (PubMed:16687656).
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. Also displays double-stranded DNA 3'-5' exonuclease, 3'-phosphodiesterase activities (PubMed:16687656, PubMed:19443450, PubMed:32516598).
Shows robust 3'-5' exonuclease activity on 3'-recessed heteroduplex DNA and is able to remove mismatched nucleotides preferentially (PubMed:16687656, PubMed:19443450).
Also exhibits 3'-5' exonuclease activity on a single nucleotide gap containing heteroduplex DNA and on blunt-ended substrates (PubMed:16687656).
Shows fairly strong 3'-phosphodiesterase activity involved in the removal of 3'-damaged termini formed in DNA by oxidative agents (PubMed:16687656, PubMed:19443450).
In the nucleus functions in the PCNA-dependent BER pathway (PubMed:11376153).
Plays a role in reversing blocked 3' DNA ends, problematic lesions that preclude DNA synthesis (PubMed:32516598).
Required for somatic hypermutation (SHM) and DNA cleavage step of class switch recombination (CSR) of immunoglobulin genes (By similarity).
Required for proper cell cycle progression during proliferation of peripheral lymphocytes (By similarity).
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. Also displays double-stranded DNA 3'-5' exonuclease, 3'-phosphodiesterase activities (PubMed:16687656, PubMed:19443450, PubMed:32516598).
Shows robust 3'-5' exonuclease activity on 3'-recessed heteroduplex DNA and is able to remove mismatched nucleotides preferentially (PubMed:16687656, PubMed:19443450).
Also exhibits 3'-5' exonuclease activity on a single nucleotide gap containing heteroduplex DNA and on blunt-ended substrates (PubMed:16687656).
Shows fairly strong 3'-phosphodiesterase activity involved in the removal of 3'-damaged termini formed in DNA by oxidative agents (PubMed:16687656, PubMed:19443450).
In the nucleus functions in the PCNA-dependent BER pathway (PubMed:11376153).
Plays a role in reversing blocked 3' DNA ends, problematic lesions that preclude DNA synthesis (PubMed:32516598).
Required for somatic hypermutation (SHM) and DNA cleavage step of class switch recombination (CSR) of immunoglobulin genes (By similarity).
Required for proper cell cycle progression during proliferation of peripheral lymphocytes (By similarity).
Catalytic activity
Cofactor
Mn2+ (UniProtKB | Rhea| CHEBI:29035 )
Note: Probably binds two magnesium or manganese ions per subunit.
Activity regulation
3'-5' exonuclease activity is activated by sodium and manganese (PubMed:16687656).
3'-5' exonuclease and 3'-phosphodiesterase activities are stimulated in presence of PCNA (PubMed:19443450).
3'-5' exonuclease and 3'-phosphodiesterase activities are stimulated in presence of PCNA (PubMed:19443450).
pH Dependence
Optimum pH is 6.0-8.0.
Features
Showing features for binding site, active site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 8 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 48 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Active site | 156 | |||||
Sequence: Y | ||||||
Active site | 197 | Proton donor/acceptor | ||||
Sequence: D | ||||||
Binding site | 197 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 199 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Site | 199 | Transition state stabilizer | ||||
Sequence: N | ||||||
Site | 277 | Important for catalytic activity | ||||
Sequence: D | ||||||
Binding site | 303 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Active site | 304 | Proton acceptor | ||||
Sequence: H | ||||||
Binding site | 304 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Site | 304 | Interaction with DNA substrate | ||||
Sequence: H | ||||||
Binding site | 469 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 472 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 495 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 509 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | fibrillar center | |
Cellular Component | intracellular membrane-bounded organelle | |
Cellular Component | mitochondrion | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Molecular Function | DNA binding | |
Molecular Function | DNA-(apurinic or apyrimidinic site) endonuclease activity | |
Molecular Function | double-stranded DNA 3'-5' DNA exonuclease activity | |
Molecular Function | endonuclease activity | |
Molecular Function | phosphoric diester hydrolase activity | |
Molecular Function | zinc ion binding | |
Biological Process | base-excision repair | |
Biological Process | DNA recombination |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDNA-(apurinic or apyrimidinic site) endonuclease 2
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9UBZ4
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Together with PCNA, is redistributed in discrete nuclear foci in presence of oxidative DNA damaging agents.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 48 | Abolished 3'-5' exonuclease activity; when associated with Asn-197. Synthetic lethality in a BRCA1 or BRCA2 mutant cell line background; when associated with Asn-197. | ||||
Sequence: E → Q | ||||||
Natural variant | VAR_023390 | 141 | in dbSNP:rs2301416 | |||
Sequence: R → C | ||||||
Natural variant | VAR_048261 | 141 | in dbSNP:rs2301416 | |||
Sequence: R → W | ||||||
Mutagenesis | 197 | Abolished 3'-5' exonuclease activity; when associated with Gln-48. Synthetic lethality in a BRCA1 or BRCA2 mutant cell line background; when associated with Gln-48. | ||||
Sequence: D → N | ||||||
Natural variant | VAR_064033 | 269 | identified in a patient with mtDNA maintenance disorders; dbSNP:rs145122391 | |||
Sequence: H → Y | ||||||
Mutagenesis | 269 | Abolishes AP endodeoxyribonuclease, 3'-5' exonuclease activity and 3'-phosphodiesterase activities. | ||||
Sequence: H → A | ||||||
Mutagenesis | 277 | Abolishes AP endodeoxyribonuclease, 3'-5' exonuclease activity and 3'-phosphodiesterase activities. | ||||
Sequence: D → A | ||||||
Natural variant | VAR_064034 | 392 | identified in a patient with mtDNA maintenance disorders; dbSNP:rs201964062 | |||
Sequence: N → H | ||||||
Mutagenesis | 396 | Reduces 3'-5' exonuclease activity in presence of PCNA. Does not abolish the 3'-5' exonuclease activity. Does only partially redistributes together with PCNA in nuclear foci in presence of oxidative-induced DNA damaging agents. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 396-397 | Loss of interaction with PCNA. | ||||
Sequence: YF → AA | ||||||
Mutagenesis | 397 | Reduces 3'-5' exonuclease activity in presence of PCNA. Does not abolish the 3'-5' exonuclease activity. Does only partially redistributes together with PCNA in nuclear foci in presence of oxidative-induced DNA damaging agents. | ||||
Sequence: F → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 430 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000200014 | 1-518 | UniProt | DNA-(apurinic or apyrimidinic site) endonuclease 2 | |||
Sequence: MLRVVSWNINGIRRPLQGVANQEPSNCAAVAVGRILDELDADIVCLQETKVTRDALTEPLAIVEGYNSYFSFSRNRSGYSGVATFCKDNATPVAAEEGLSGLFATQNGDVGCYGNMDEFTQEELRALDSEGRALLTQHKIRTWEGKEKTLTLINVYCPHADPGRPERLVFKMRFYRLLQIRAEALLAAGSHVIILGDLNTAHRPIDHWDAVNLECFEEDPGRKWMDSLLSNLGCQSASHVGPFIDSYRCFQPKQEGAFTCWSAVTGARHLNYGSRLDYVLGDRTLVIDTFQASFLLPEVMGSDHCPVGAVLSVSSVPAKQCPPLCTRFLPEFAGTQLKILRFLVPLEQSPVLEQSTLQHNNQTRVQTCQNKAQVRSTRPQPSQVGSSRGQKNLKSYFQPSPSCPQASPDIELPSLPLMSALMTPKTPEEKAVAKVVKGQAKTSEAKDEKELRTSFWKSVLAGPLRTPLCGGHREPCVMRTVKKPGPNLGRRFYMCARPRGPPTDPSSRCNFFLWSRPS | |||||||
Modified residue (large scale data) | 227 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 246 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 247 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 349 | PRIDE | Phosphoserine | ||||
Sequence: S |
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in brain and kidney. Weakly expressed in the fetal brain.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with PCNA; this interaction is triggered by reactive oxygen species and increased by misincorporation of uracil in nuclear DNA.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9UBZ4 | APBA2 Q99767 | 3 | EBI-742588, EBI-81711 | |
BINARY | Q9UBZ4 | MKRN3 Q13064 | 3 | EBI-742588, EBI-2340269 | |
BINARY | Q9UBZ4 | TSHZ3 Q63HK5 | 3 | EBI-742588, EBI-9053916 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, zinc finger.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 355-407 | Disordered | ||||
Sequence: STLQHNNQTRVQTCQNKAQVRSTRPQPSQVGSSRGQKNLKSYFQPSPSCPQAS | ||||||
Region | 390-397 | Required for the interaction and colocalization with PCNA in nuclear foci in presence of oxidative-induced DNA damaging agents | ||||
Sequence: QKNLKSYF | ||||||
Zinc finger | 469-518 | GRF-type | ||||
Sequence: CGGHREPCVMRTVKKPGPNLGRRFYMCARPRGPPTDPSSRCNFFLWSRPS |
Domain
The PCNA interacting protein (PIP) box mediates interaction with PCNA and recruitment to DNA single-strand breaks.
Sequence similarities
Belongs to the DNA repair enzymes AP/ExoA family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length518
- Mass (Da)57,401
- Last updated2000-05-01 v1
- Checksum08464806153F8832
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 399 | in Ref. 4; AAD43041 | ||||
Sequence: P → S |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB049211 EMBL· GenBank· DDBJ | BAB13764.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ011311 EMBL· GenBank· DDBJ | CAB45242.1 EMBL· GenBank· DDBJ | mRNA | ||
AB021260 EMBL· GenBank· DDBJ | BAA78422.1 EMBL· GenBank· DDBJ | mRNA | ||
AF119046 EMBL· GenBank· DDBJ | AAD43041.1 EMBL· GenBank· DDBJ | mRNA | ||
AY884244 EMBL· GenBank· DDBJ | AAW56941.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AL020991 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC002959 EMBL· GenBank· DDBJ | AAH02959.1 EMBL· GenBank· DDBJ | mRNA |