ID   APEX1_MOUSE             Reviewed;         317 AA.
AC   P28352;
DT   01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   04-NOV-2026, entry version 229.
DE   RecName: Full=DNA repair nuclease/redox regulator APEX1;
DE            EC=3.1.11.2 {ECO:0000250|UniProtKB:P27695};
DE            EC=3.1.21.- {ECO:0000250|UniProtKB:P27695};
DE   AltName: Full=APEX nuclease;
DE            Short=APEN;
DE   AltName: Full=Apurinic-apyrimidinic endonuclease 1;
DE            Short=AP endonuclease 1;
DE   AltName: Full=Redox factor-1;
DE            Short=REF-1;
DE   Contains:
DE     RecName: Full=DNA repair nuclease/redox regulator APEX1, mitochondrial;
GN   Name=Apex1; Synonyms=Ape, Apex, Ref1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=NFS; TISSUE=Spleen;
RX   PubMed=1939131; DOI=10.1016/s0021-9258(18)54779-7;
RA   Seki S., Akiyama K., Watanabe S., Hatsushika M., Ikeda S., Tsutsui K.;
RT   "cDNA and deduced amino acid sequence of a mouse DNA repair enzyme (APEX
RT   nuclease) with significant homology to Escherichia coli exonuclease III.";
RL   J. Biol. Chem. 266:20797-20802(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=129; TISSUE=Embryo;
RX   PubMed=7533013; DOI=10.1007/bf00426079;
RA   Takiguchi Y., Chen D.J.;
RT   "Genomic structure of the mouse apurinic/apyrimidinic endonuclease gene.";
RL   Mamm. Genome 5:717-722(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=BALB/cJ; TISSUE=Blood;
RX   PubMed=7782087; DOI=10.1016/0888-7543(95)80083-x;
RA   Akiyama K., Nagao K., Oshida T., Tsutsui K., Yoshida M.C., Seki S.;
RT   "Cloning, sequence analysis, and chromosomal assignment of the mouse Apex
RT   gene.";
RL   Genomics 26:63-69(1995).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   PROTEIN SEQUENCE OF 2-22, AND CHARACTERIZATION.
RC   TISSUE=Ascites;
RX   PubMed=1716153; DOI=10.1016/0167-4838(91)90024-t;
RA   Seki S., Ikeda S., Watanabe S., Hatsushika M., Tsutsui K., Akiyama K.,
RA   Zhang B.;
RT   "A mouse DNA repair enzyme (APEX nuclease) having exonuclease and
RT   apurinic/apyrimidinic endonuclease activities: purification and
RT   characterization.";
RL   Biochim. Biophys. Acta 1079:57-64(1991).
RN   [6]
RP   SUBCELLULAR LOCATION.
RX   PubMed=16617147; DOI=10.1093/nar/gkl177;
RA   Chattopadhyay R., Wiederhold L., Szczesny B., Boldogh I., Hazra T.K.,
RA   Izumi T., Mitra S.;
RT   "Identification and characterization of mitochondrial abasic (AP)-
RT   endonuclease in mammalian cells.";
RL   Nucleic Acids Res. 34:2067-2076(2006).
RN   [7]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=18025127; DOI=10.1084/jem.20071289;
RA   Guikema J.E., Linehan E.K., Tsuchimoto D., Nakabeppu Y., Strauss P.R.,
RA   Stavnezer J., Schrader C.E.;
RT   "APE1- and APE2-dependent DNA breaks in immunoglobulin class switch
RT   recombination.";
RL   J. Exp. Med. 204:3017-3026(2007).
RN   [8]
RP   CAUTION.
RX   PubMed=19556307; DOI=10.1093/intimm/dxp061;
RA   Sabouri Z., Okazaki I.M., Shinkura R., Begum N., Nagaoka H., Tsuchimoto D.,
RA   Nakabeppu Y., Honjo T.;
RT   "Apex2 is required for efficient somatic hypermutation but not for class
RT   switch recombination of immunoglobulin genes.";
RL   Int. Immunol. 21:947-955(2009).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [10]
RP   PHOSPHORYLATION AT THR-232, INTERACTION WITH CDK5, AND MUTAGENESIS OF
RP   SER-53 AND THR-232.
RX   PubMed=20473298; DOI=10.1038/ncb2058;
RA   Huang E., Qu D., Zhang Y., Venderova K., Haque M.E., Rousseaux M.W.C.,
RA   Slack R.S., Woulfe J.M., Park D.S.;
RT   "The role of Cdk5-mediated apurinic/apyrimidinic endonuclease 1
RT   phosphorylation in neuronal death.";
RL   Nat. Cell Biol. 12:563-571(2010).
RN   [11]
RP   FUNCTION.
RX   PubMed=23382073; DOI=10.1128/mcb.00026-13;
RA   Masani S., Han L., Yu K.;
RT   "Apurinic/apyrimidinic endonuclease 1 is the essential nuclease during
RT   immunoglobulin class switch recombination.";
RL   Mol. Cell. Biol. 33:1468-1473(2013).
CC   -!- FUNCTION: Multifunctional protein that plays a central role in the
CC       cellular response to oxidative stress. The two major activities of
CC       APEX1 are DNA repair and redox regulation of transcriptional factors
CC       (By similarity). Functions as an apurinic/apyrimidinic (AP)
CC       endodeoxyribonuclease in the base excision repair (BER) pathway of DNA
CC       lesions induced by oxidative and alkylating agents. Initiates repair of
CC       AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester
CC       backbone immediately adjacent to the damage, generating a single-strand
CC       break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Also incises
CC       at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA
CC       regions of R-loop structures, and single-stranded RNA molecules (By
CC       similarity). Operates at switch sites of immunoglobulin (Ig) constant
CC       regions where it mediates Ig isotype class switch recombination.
CC       Processes AP sites induced by successive action of AICDA and UNG.
CC       Generates staggered nicks in opposite DNA strands resulting in the
CC       formation of double-strand DNA breaks that are finally resolved via
CC       non-homologous end joining repair pathway (PubMed:18025127,
CC       PubMed:23382073). Has 3'-5' exodeoxyribonuclease activity on mismatched
CC       deoxyribonucleotides at the 3' termini of nicked or gapped DNA
CC       molecules during short-patch BER (By similarity). Possesses DNA 3'
CC       phosphodiesterase activity capable of removing lesions (such as
CC       phosphoglycolate and 8-oxoguanine) blocking the 3' side of DNA strand
CC       breaks (By similarity). Also acts as an endoribonuclease involved in
CC       the control of single-stranded RNA metabolism. Plays a role in
CC       regulating MYC mRNA turnover by preferentially cleaving in between UA
CC       and CA dinucleotides of the MYC coding region determinant (CRD). In
CC       association with NMD1, plays a role in the rRNA quality control process
CC       during cell cycle progression (By similarity). Acts as a loading factor
CC       for POLB onto non-incised AP sites in DNA and stimulates the 5'-
CC       terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB (By
CC       similarity). Exerts reversible nuclear redox activity to regulate DNA
CC       binding affinity and transcriptional activity of transcriptional
CC       factors by controlling the redox status of their DNA-binding domain,
CC       such as the FOS/JUN AP-1 complex after exposure to IR (By similarity).
CC       Involved in calcium-dependent down-regulation of parathyroid hormone
CC       (PTH) expression by binding to negative calcium response elements
CC       (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates
CC       with nCaRE, acting as an activator of transcriptional repression (By
CC       similarity). May also play a role in the epigenetic regulation of gene
CC       expression by participating in DNA demethylation (By similarity).
CC       Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at
CC       Lys-6 and Lys-7, leading to drug resistance (By similarity). Plays a
CC       role in protection from granzyme-mediated cellular repair leading to
CC       cell death (By similarity). Binds DNA and RNA. Associates, together
CC       with YBX1, on the MDR1 promoter. Together with NPM1, associates with
CC       rRNA (By similarity). {ECO:0000250|UniProtKB:P27695,
CC       ECO:0000269|PubMed:18025127, ECO:0000269|PubMed:23382073}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a deoxyribonucleotide-2'-deoxyribose-5'-monophosphate-DNA +
CC         H2O = a 5'-end 2'-deoxyribose-5'-monophosphate-DNA + a 3'-end 2'-
CC         deoxyribonucleotide-DNA + H(+); Xref=Rhea:RHEA:81527, Rhea:RHEA-
CC         COMP:13863, Rhea:RHEA-COMP:19699, Rhea:RHEA-COMP:19703,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:138148,
CC         ChEBI:CHEBI:231912, ChEBI:CHEBI:231913;
CC         Evidence={ECO:0000250|UniProtKB:P27695};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:81528;
CC         Evidence={ECO:0000250|UniProtKB:P27695};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Exonucleolytic cleavage in the 3'- to 5'-direction to yield
CC         nucleoside 5'-phosphates.; EC=3.1.11.2;
CC         Evidence={ECO:0000250|UniProtKB:P27695};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 3'-end 2'-deoxyribonucleotide-3'-phosphoglycolate-DNA + H2O
CC         = 2-phosphoglycolate + a 3'-end 2'-deoxyribonucleotide-DNA + H(+);
CC         Xref=Rhea:RHEA:81467, Rhea:RHEA-COMP:13863, Rhea:RHEA-COMP:19686,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58033,
CC         ChEBI:CHEBI:138148, ChEBI:CHEBI:231894;
CC         Evidence={ECO:0000250|UniProtKB:P27695};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:81468;
CC         Evidence={ECO:0000250|UniProtKB:P27695};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 3'-end 2'-deoxyribonucleotide-8-oxoguanine-DNA + H2O = 8-
CC         oxo-dGMP + a 3'-end 2'-deoxyribonucleotide-DNA + H(+);
CC         Xref=Rhea:RHEA:81471, Rhea:RHEA-COMP:13863, Rhea:RHEA-COMP:19687,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:63224,
CC         ChEBI:CHEBI:138148, ChEBI:CHEBI:231896;
CC         Evidence={ECO:0000250|UniProtKB:P27695};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:81472;
CC         Evidence={ECO:0000250|UniProtKB:P27695};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:P27695};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000250|UniProtKB:P27695};
CC       Note=Probably binds two magnesium or manganese ions per subunit.
CC       {ECO:0000250|UniProtKB:P27695};
CC   -!- ACTIVITY REGULATION: NPM1 stimulates endodeoxyribonuclease activity on
CC       double-stranded DNA with AP sites, but inhibits endoribonuclease
CC       activity on single-stranded RNA containing AP sites.
CC       {ECO:0000250|UniProtKB:P27695}.
CC   -!- SUBUNIT: Monomer. Homodimer; disulfide-linked. Component of the SET
CC       complex, composed of at least APEX1, SET, ANP32A, HMGB2, NME1 and
CC       TREX1. Associates with the dimer XRCC5/XRCC6 in a DNA-dependent manner.
CC       Interacts with SIRT1; the interaction is increased in the context of
CC       genotoxic stress. Interacts with HDAC1, HDAC2 and HDAC3; the
CC       interactions are not dependent on the APEX1 acetylation status.
CC       Interacts with XRCC1; the interaction is induced by SIRT1 and increased
CC       with the APEX1 acetylated form. Interacts with NPM1 (via N-terminal
CC       domain); the interaction is RNA-dependent and decreases in hydrogen
CC       peroxide-damaged cells. Interacts (via N-terminus) with YBX1 (via C-
CC       terminus); the interaction is increased in presence of APEX1 acetylated
CC       at Lys-6 and Lys-7. Interacts with HNRNPL; the interaction is DNA-
CC       dependent. Interacts (via N-terminus) with KPNA1 and KPNA2. Interacts
CC       with TXN; the interaction stimulates the FOS/JUN AP-1 complex DNA-
CC       binding activity in a redox-dependent manner. Interacts with GZMA,
CC       KRT8, MDM2, POLB, PRDX6, PRPF19, RPLP0, TOMM20 and WDR77 (By
CC       similarity). Binds to CDK5 (PubMed:20473298).
CC       {ECO:0000250|UniProtKB:P27695, ECO:0000269|PubMed:20473298}.
CC   -!- SUBCELLULAR LOCATION: Nucleus. Nucleus, nucleolus {ECO:0000250}.
CC       Nucleus speckle {ECO:0000255|PROSITE-ProRule:PRU00764}. Endoplasmic
CC       reticulum {ECO:0000250}. Cytoplasm. Note=Colocalized with SIRT1 in the
CC       nucleus. Colocalized with YBX1 in nuclear speckles after genotoxic
CC       stress. Together with OGG1 is recruited to nuclear speckles in UVA-
CC       irradiated cells. Colocalized with nucleolin and NPM1 in the nucleolus.
CC       Its nucleolar localization is cell cycle dependent and requires active
CC       rRNA transcription. Colocalized with calreticulin in the endoplasmic
CC       reticulum. Translocation from the nucleus to the cytoplasm is
CC       stimulated in presence of nitric oxide (NO) and function in a CRM1-
CC       dependent manner, possibly as a consequence of demasking a nuclear
CC       export signal (amino acid position 63-79). S-nitrosylation at Cys-92
CC       and Cys-309 regulates its nuclear-cytosolic shuttling. Ubiquitinated
CC       form is localized predominantly in the cytoplasm. Detected in the
CC       cytoplasm of B-cells stimulated to switch (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [DNA repair nuclease/redox regulator APEX1,
CC       mitochondrial]: Mitochondrion. Note=Translocation from the cytoplasm to
CC       the mitochondria is mediated by ROS signaling and cleavage mediated by
CC       granzyme A. Tom20-dependent translocated mitochondrial APEX1 level is
CC       significantly increased after genotoxic stress (By similarity). The
CC       cleaved APEX2 is only detected in mitochondria. {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed in both resting and stimulated B cells
CC       stimulated to switch (at protein level).
CC   -!- DOMAIN: The N-terminus contains the redox activity while the C-terminus
CC       exerts the DNA AP-endodeoxyribonuclease activity; both function are
CC       independent in their actions. An unconventional mitochondrial targeting
CC       sequence (MTS) is harbored within the C-terminus, that appears to be
CC       masked by the N-terminal sequence containing the nuclear localization
CC       signal (NLS), that probably blocks the interaction between the MTS and
CC       Tom proteins (By similarity). {ECO:0000250}.
CC   -!- PTM: Phosphorylated. Phosphorylation by kinase PKC or casein kinase CK2
CC       results in enhanced redox activity that stimulates binding of the
CC       FOS/JUN AP-1 complex to its cognate binding site. AP-
CC       endodeoxyribonuclease activity is not affected by CK2-mediated
CC       phosphorylation (By similarity). Phosphorylation of Thr-232 by CDK5 in
CC       response to MPP(+)/MPTP (1-methyl-4-phenylpyridinium) reduces AP-
CC       endodeoxyribonuclease activity resulting in accumulation of DNA damage
CC       and contributing to neuronal death. {ECO:0000250|UniProtKB:P27695,
CC       ECO:0000269|PubMed:20473298}.
CC   -!- PTM: Acetylated on Lys-6 and Lys-7. Acetylation is increased by the
CC       transcriptional coactivator EP300 acetyltransferase, genotoxic agents
CC       like H(2)O(2) and methyl methanesulfonate (MMS). Acetylation increases
CC       its binding affinity to the negative calcium response element (nCaRE)
CC       DNA promoter. The acetylated form induces a stronger binding of YBX1 to
CC       the Y-box sequence in the MDR1 promoter than the unacetylated form.
CC       Deacetylated on lysines. Lys-6 and Lys-7 are deacetylated by SIRT1 (By
CC       similarity). {ECO:0000250|UniProtKB:P27695}.
CC   -!- PTM: Cleaved at Lys-30 by granzyme A to create the mitochondrial form;
CC       leading in reduction of binding to DNA, AP endodeoxyribonuclease
CC       activity, redox activation of transcription factors and to enhanced
CC       cell death. Cleaved by granzyme K; leading to intracellular ROS
CC       accumulation and enhanced cell death after oxidative stress (By
CC       similarity). {ECO:0000250|UniProtKB:P27695}.
CC   -!- PTM: Cys-64 and Cys-92 are nitrosylated in response to nitric oxide
CC       (NO) and lead to the exposure of the nuclear export signal (NES).
CC       {ECO:0000250|UniProtKB:P27695}.
CC   -!- PTM: Ubiquitinated by MDM2; leading to translocation to the cytoplasm
CC       and proteasomal degradation. {ECO:0000250|UniProtKB:P27695}.
CC   -!- MISCELLANEOUS: The specific activity of the cleaved mitochondrial
CC       endodeoxyribonuclease appears to be about 3-fold higher than of the
CC       full-length form. Extract of mitochondria, but not of nuclei or
CC       cytosol, cleaves recombinant APEX1 to generate a mitochondrial APEX1-
CC       sized product (By similarity). {ECO:0000250|UniProtKB:P23196}.
CC   -!- SIMILARITY: Belongs to the DNA repair enzymes AP/ExoA family.
CC       {ECO:0000305}.
CC   -!- CAUTION: The efficiency of Ig isotype class switch recombination is not
CC       affected by transient APEX1 knockdown. {ECO:0000269|PubMed:19556307}.
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DR   EMBL; D90374; BAA14382.1; -; mRNA.
DR   EMBL; U12273; AAC13769.1; -; Genomic_DNA.
DR   EMBL; D38077; BAA07270.1; -; Genomic_DNA.
DR   EMBL; BC052401; AAH52401.1; -; mRNA.
DR   CCDS; CCDS27027.1; -.
DR   PIR; A39500; A39500.
DR   RefSeq; NP_033817.1; NM_009687.2.
DR   PDB; 7CD5; X-ray; 2.70 A; A=1-317.
DR   PDB; 7CD6; X-ray; 2.70 A; A=31-317.
DR   AlphaFoldDB; P28352; -.
DR   SMR; P28352; -.
DR   BioGRID; 198145; 19.
DR   ELM; P28352; -.
DR   FunCoup; P28352; 2581.
DR   IntAct; P28352; 3.
DR   STRING; 10090.ENSMUSP00000042602; -.
DR   GlyGen; P28352; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P28352; -.
DR   PhosphoSitePlus; P28352; -.
DR   SwissPalm; P28352; -.
DR   jPOST; P28352; -.
DR   PaxDb; 10090-ENSMUSP00000042602; -.
DR   PeptideAtlas; P28352; -.
DR   ProteomicsDB; 281828; -.
DR   Pumba; P28352; -.
DR   Antibodypedia; 62; 1094 antibodies from 50 providers.
DR   DNASU; 11792; -.
DR   Ensembl; ENSMUST00000049411.12; ENSMUSP00000042602.6; ENSMUSG00000035960.15.
DR   GeneID; 11792; -.
DR   KEGG; mmu:11792; -.
DR   UCSC; uc007tly.2; mouse.
DR   AGR; MGI:88042; -.
DR   CTD; 328; -.
DR   MGI; MGI:88042; Apex1.
DR   VEuPathDB; HostDB:ENSMUSG00000035960; -.
DR   eggNOG; KOG1294; Eukaryota.
DR   GeneTree; ENSGT00530000063540; -.
DR   HOGENOM; CLU_027539_1_3_1; -.
DR   InParanoid; P28352; -.
DR   OMA; AAEYTWW; -.
DR   OrthoDB; 498125at2759; -.
DR   PhylomeDB; P28352; -.
DR   BRENDA; 4.2.99.18; 3474.
DR   Reactome; R-MMU-110357; Displacement of DNA glycosylase by APEX1.
DR   Reactome; R-MMU-110362; POLB-Dependent Long Patch Base Excision Repair.
DR   Reactome; R-MMU-110373; Resolution of AP sites via the multiple-nucleotide patch replacement pathway.
DR   Reactome; R-MMU-5651801; PCNA-Dependent Long Patch Base Excision Repair.
DR   Reactome; R-MMU-73930; Abasic sugar-phosphate removal via the single-nucleotide replacement pathway.
DR   Reactome; R-MMU-73933; Resolution of Abasic Sites (AP sites).
DR   BioGRID-ORCS; 11792; 11 hits in 118 CRISPR screens.
DR   PRO; PR:P28352; -.
DR   Proteomes; UP000000589; Chromosome 14.
DR   RNAct; P28352; protein.
DR   Bgee; ENSMUSG00000035960; Expressed in primitive streak and 302 other cell types or tissues.
DR   ExpressionAtlas; P28352; baseline and differential.
DR   GO; GO:0005813; C:centrosome; ISO:GO_Central.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR   GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR   GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR   GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005667; C:transcription regulator complex; ISO:GO_Central.
DR   GO; GO:0008408; F:3'-5' exonuclease activity; ISS:UniProtKB.
DR   GO; GO:0008296; F:3'-5'-DNA exonuclease activity; ISO:GO_Central.
DR   GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB.
DR   GO; GO:0052720; F:class II DNA-(apurinic or apyrimidinic site) endonuclease activity; ISS:UniProtKB.
DR   GO; GO:0003684; F:damaged DNA binding; ISS:UniProtKB.
DR   GO; GO:0033892; F:deoxyribonuclease (pyrimidine dimer) activity; ISO:GO_Central.
DR   GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR   GO; GO:0140431; F:DNA-(abasic site) binding; ISS:UniProtKB.
DR   GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) endonuclease activity; ISS:UniProtKB.
DR   GO; GO:0008311; F:double-stranded DNA 3'-5' DNA exonuclease activity; ISS:UniProtKB.
DR   GO; GO:0008309; F:double-stranded DNA exodeoxyribonuclease activity; ISO:GO_Central.
DR   GO; GO:0003691; F:double-stranded telomeric DNA binding; ISO:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; ISS:UniProtKB.
DR   GO; GO:0051059; F:NF-kappaB binding; ISO:GO_Central.
DR   GO; GO:0016491; F:oxidoreductase activity; ISS:UniProtKB.
DR   GO; GO:0090580; F:phosphodiesterase activity, acting on 3'-phosphoglycolate-terminated DNA strands; ISO:GO_Central.
DR   GO; GO:0008081; F:phosphoric diester hydrolase activity; ISO:GO_Central.
DR   GO; GO:0044877; F:protein-containing complex binding; ISO:GO_Central.
DR   GO; GO:0004521; F:RNA endonuclease activity; ISO:GO_Central.
DR   GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR   GO; GO:0006284; P:base-excision repair; ISO:GO_Central.
DR   GO; GO:0045454; P:cell redox homeostasis; IDA:MGI.
DR   GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:GO_Central.
DR   GO; GO:0006308; P:DNA catabolic process; ISO:GO_Central.
DR   GO; GO:0006281; P:DNA repair; ISS:UniProtKB.
DR   GO; GO:0014912; P:negative regulation of smooth muscle cell migration; ISO:GO_Central.
DR   GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; ISO:GO_Central.
DR   GO; GO:0044029; P:positive regulation of gene expression via chromosomal CpG island demethylation; ISS:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:GO_Central.
DR   GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR   GO; GO:0043488; P:regulation of mRNA stability; ISS:UniProtKB.
DR   GO; GO:0000723; P:telomere maintenance; ISO:GO_Central.
DR   GO; GO:0097698; P:telomere maintenance via base-excision repair; ISO:GO_Central.
DR   CDD; cd09087; Ape1-like_AP-endo; 1.
DR   FunFam; 3.60.10.10:FF:000009; DNA-(apurinic or apyrimidinic site) lyase; 1.
DR   Gene3D; 3.60.10.10; Endonuclease/exonuclease/phosphatase; 1.
DR   InterPro; IPR004808; AP_endonuc_1.
DR   InterPro; IPR020847; AP_endonuclease_F1_BS.
DR   InterPro; IPR020848; AP_endonuclease_F1_CS.
DR   InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR   InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR   NCBIfam; TIGR00195; exoDNase_III; 1.
DR   NCBIfam; TIGR00633; xth; 1.
DR   PANTHER; PTHR22748; AP ENDONUCLEASE; 1.
DR   PANTHER; PTHR22748:SF6; DNA-(APURINIC OR APYRIMIDINIC SITE) ENDONUCLEASE; 1.
DR   Pfam; PF03372; Exo_endo_phos; 1.
DR   SUPFAM; SSF56219; DNase I-like; 1.
DR   PROSITE; PS00726; AP_NUCLEASE_F1_1; 1.
DR   PROSITE; PS00727; AP_NUCLEASE_F1_2; 1.
DR   PROSITE; PS00728; AP_NUCLEASE_F1_3; 1.
DR   PROSITE; PS51435; AP_NUCLEASE_F1_4; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Activator; Cleavage on pair of basic residues;
KW   Cytoplasm; Direct protein sequencing; Disulfide bond; DNA damage;
KW   DNA recombination; DNA repair; DNA-binding; Endonuclease;
KW   Endoplasmic reticulum; Exonuclease; Hydrolase; Magnesium; Metal-binding;
KW   Mitochondrion; Nuclease; Nucleus; Phosphoprotein; Reference proteome;
KW   Repressor; RNA-binding; S-nitrosylation; Transcription;
KW   Transcription regulation; Ubl conjugation.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:1716153"
FT   CHAIN           2..317
FT                   /note="DNA repair nuclease/redox regulator APEX1"
FT                   /id="PRO_0000200011"
FT   CHAIN           31..317
FT                   /note="DNA repair nuclease/redox regulator APEX1,
FT                   mitochondrial"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000402573"
FT   REGION          1..58
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2..32
FT                   /note="Necessary for interaction with YBX1, binding to RNA,
FT                   association together with NPM1 to rRNA, endoribonuclease
FT                   activity on abasic RNA and localization in the nucleoli"
FT                   /evidence="ECO:0000250"
FT   REGION          22..32
FT                   /note="Necessary for interaction with NPM1 and for
FT                   efficient rRNA binding"
FT                   /evidence="ECO:0000250"
FT   REGION          288..317
FT                   /note="Mitochondrial targeting sequence (MTS)"
FT                   /evidence="ECO:0000250"
FT   MOTIF           8..12
FT                   /note="Nuclear localization signal (NLS)"
FT                   /evidence="ECO:0000250"
FT   MOTIF           63..79
FT                   /note="Nuclear export signal (NES)"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        15..37
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        170
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        209
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         69
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         95
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         209
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         211
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         307
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   SITE            30..31
FT                   /note="Cleavage; by granzyme A"
FT                   /evidence="ECO:0000250"
FT   SITE            211
FT                   /note="Important for substrate recognition"
FT                   /evidence="ECO:0000250"
FT   SITE            211
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250"
FT   SITE            282
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000250"
FT   SITE            308
FT                   /note="Interaction with DNA substrate"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         6
FT                   /note="N6-acetyllysine; by EP300"
FT                   /evidence="ECO:0000250|UniProtKB:P27695"
FT   MOD_RES         7
FT                   /note="N6-acetyllysine; by EP300"
FT                   /evidence="ECO:0000250|UniProtKB:P27695"
FT   MOD_RES         18
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         26
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P27695"
FT   MOD_RES         30
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P27695"
FT   MOD_RES         31
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P27695"
FT   MOD_RES         34
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P27695"
FT   MOD_RES         53
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P27695"
FT   MOD_RES         64
FT                   /note="S-nitrosocysteine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P27695"
FT   MOD_RES         92
FT                   /note="S-nitrosocysteine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P27695"
FT   MOD_RES         196
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P27695"
FT   MOD_RES         232
FT                   /note="Phosphothreonine; by CDK5"
FT                   /evidence="ECO:0000269|PubMed:20473298"
FT   MOD_RES         309
FT                   /note="S-nitrosocysteine"
FT                   /evidence="ECO:0000250|UniProtKB:P27695"
FT   DISULFID        64..92
FT                   /note="Alternate"
FT                   /evidence="ECO:0000250"
FT   MUTAGEN         53
FT                   /note="S->A: Reduced CDK5-mediated phosphorylation. Loss of
FT                   CDK5-mediated phosphorylation; when associated with T-232."
FT                   /evidence="ECO:0000269|PubMed:20473298"
FT   MUTAGEN         232
FT                   /note="T->A: Reduced CDK5-mediated phosphorylation. Confers
FT                   neuron resistance to MPP(+)/MPTP
FT                   (1-methyl-4-phenylpyridinium). Loss of CDK5-mediated
FT                   phosphorylation; when associated with S-53."
FT                   /evidence="ECO:0000269|PubMed:20473298"
FT   MUTAGEN         232
FT                   /note="T->E: Confers neuron sensitivity to MPP(+)/MPTP
FT                   (1-methyl-4-phenylpyridinium)."
FT                   /evidence="ECO:0000269|PubMed:20473298"
FT   HELIX           46..49
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   STRAND          61..67
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   HELIX           71..76
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   HELIX           79..86
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   STRAND          89..94
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   HELIX           100..102
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   HELIX           105..108
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   STRAND          115..119
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   STRAND          125..127
FT                   /evidence="ECO:0007829|PDB:7CD6"
FT   STRAND          130..136
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   STRAND          139..144
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   HELIX           148..150
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   STRAND          151..153
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   STRAND          156..160
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   STRAND          165..170
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   HELIX           176..178
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   HELIX           181..201
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   STRAND          204..209
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   HELIX           216..218
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   HELIX           223..225
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   HELIX           233..245
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   STRAND          248..250
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   HELIX           251..255
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   STRAND          264..266
FT                   /evidence="ECO:0007829|PDB:7CD6"
FT   HELIX           269..271
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   TURN            272..276
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   STRAND          282..287
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   HELIX           288..293
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   STRAND          294..299
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   STRAND          305..308
FT                   /evidence="ECO:0007829|PDB:7CD5"
FT   STRAND          311..315
FT                   /evidence="ECO:0007829|PDB:7CD5"
SQ   SEQUENCE   317 AA;  35490 MW;  CF086691FAC89C4A CRC64;
     MPKRGKKAAA DDGEEPKSEP ETKKSKGAAK KTEKEAAGEG PVLYEDPPDQ KTSPSGKSAT
     LKICSWNVDG LRAWIKKKGL DWVKEEAPDI LCLQETKCSE NKLPAELQEL PGLTHQYWSA
     PSDKEGYSGV GLLSRQCPLK VSYGIGEEEH DQEGRVIVAE FESFVLVTAY VPNAGRGLVR
     LEYRQRWDEA FRKFLKDLAS RKPLVLCGDL NVAHEEIDLR NPKGNKKNAG FTPQERQGFG
     ELLQAVPLAD SFRHLYPNTA YAYTFWTYMM NARSKNVGWR LDYFLLSHSL LPALCDSKIR
     SKALGSDHCP ITLYLAL
//