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 27-MAR-2024, entry version 218. 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=REF-1; DE AltName: Full=Redox factor-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 FUNCTION. 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 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). 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 Functions as an apurinic/apyrimidinic (AP) endodeoxyribonuclease in the CC DNA base excision repair (BER) pathway of DNA lesions induced by CC oxidative and alkylating agents. Initiates repair of AP sites in DNA by CC catalyzing hydrolytic incision of the phosphodiester backbone CC immediately adjacent to the damage, generating a single-strand break CC with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Also incises at AP CC sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions CC of R-loop structures, and single-stranded RNA molecules. Has 3'-5' CC exoribonuclease activity on mismatched deoxyribonucleotides at the 3' CC termini of nicked or gapped DNA molecules during short-patch BER. CC Possesses DNA 3' phosphodiesterase activity capable of removing lesions CC (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. CC May also play a role in the epigenetic regulation of gene expression by CC participating in DNA demethylation. Acts as a loading factor for POLB CC onto non-incised AP sites in DNA and stimulates the 5'-terminal CC deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role CC in the protection from granzyme-mediated cellular repair leading to CC cell death. Also involved in the DNA cleavage step of class switch CC recombination (CSR). On the other hand, APEX1 also exerts reversible CC nuclear redox activity to regulate DNA binding affinity and CC transcriptional activity of transcriptional factors by controlling the CC redox status of their DNA-binding domain, such as the FOS/JUN AP-1 CC complex after exposure to IR. Involved in calcium-dependent down- CC regulation of parathyroid hormone (PTH) expression by binding to CC negative calcium response elements (nCaREs). Together with HNRNPL or CC the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of CC transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter CC activity, when acetylated at Lys-6 and Lys-7, leading to drug CC resistance. Acts also as an endoribonuclease involved in the control of CC single-stranded RNA metabolism. Plays a role in regulating MYC mRNA CC turnover by preferentially cleaving in between UA and CA dinucleotides CC of the MYC coding region determinant (CRD). In association with NMD1, CC plays a role in the rRNA quality control process during cell cycle CC progression. Associates, together with YBX1, on the MDR1 promoter. CC Together with NPM1, associates with rRNA. Binds DNA and RNA. CC {ECO:0000269|PubMed:18025127, ECO:0000269|PubMed:19556307}. 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 -!- 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDBsum; 7CD5; -. DR PDBsum; 7CD6; -. DR AlphaFoldDB; P28352; -. DR SMR; P28352; -. DR BioGRID; 198145; 19. DR ELM; P28352; -. DR IntAct; P28352; 3. DR STRING; 10090.ENSMUSP00000042602; -. DR iPTMnet; P28352; -. DR PhosphoSitePlus; P28352; -. DR SwissPalm; P28352; -. DR EPD; P28352; -. DR jPOST; P28352; -. DR PaxDb; 10090-ENSMUSP00000042602; -. DR PeptideAtlas; P28352; -. DR ProteomicsDB; 281828; -. DR Pumba; P28352; -. DR Antibodypedia; 62; 1100 antibodies from 46 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; WWSYRGR; -. DR OrthoDB; 161558at2759; -. DR PhylomeDB; P28352; -. DR TreeFam; TF315048; -. 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 ChiTaRS; Apex1; mouse. 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:MGI. 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:MGI. DR GO; GO:0008408; F:3'-5' exonuclease activity; ISS:UniProtKB. DR GO; GO:0008296; F:3'-5'-DNA exonuclease activity; ISO:MGI. 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: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; IBA:GO_Central. DR GO; GO:0008309; F:double-stranded DNA exodeoxyribonuclease activity; ISO:MGI. DR GO; GO:0003691; F:double-stranded telomeric DNA binding; ISO:MGI. DR GO; GO:0046872; F:metal ion binding; ISS:UniProtKB. DR GO; GO:0051059; F:NF-kappaB binding; ISO:MGI. DR GO; GO:0016491; F:oxidoreductase activity; ISS:UniProtKB. DR GO; GO:0090580; F:phosphodiesterase activity, acting on 3'-phosphoglycolate-terminated DNA strands; ISO:MGI. DR GO; GO:0008081; F:phosphoric diester hydrolase activity; ISO:MGI. DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:0004521; F:RNA endonuclease activity; ISO:MGI. DR GO; GO:0016890; F:site-specific endodeoxyribonuclease activity, specific for altered base; ISS:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB. DR GO; GO:0006284; P:base-excision repair; ISO:MGI. DR GO; GO:0045454; P:cell redox homeostasis; IDA:MGI. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:MGI. DR GO; GO:0006308; P:DNA catabolic process; ISO:MGI. DR GO; GO:0080111; P:DNA demethylation; ISS:UniProtKB. DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW. DR GO; GO:0006281; P:DNA repair; ISS:UniProtKB. DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; ISO:MGI. DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; ISO:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI. 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:MGI. DR GO; GO:0097698; P:telomere maintenance via base-excision repair; ISO:MGI. DR CDD; cd09087; Ape1-like_AP-endo; 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. DR Genevisible; P28352; MM. 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 1..40 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 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 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 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 //