APEX1_MOUSE
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 03-AUG-2022, entry version 209.
DE RecName: Full=DNA-(apurinic or apyrimidinic site) endonuclease;
DE EC=3.1.11.2 {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-(apurinic or apyrimidinic site) endonuclease, 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, Pancreas,
RC 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 a 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. Does also incise at
CC AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA
CC regions of R-loop structures, and single-stranded RNA molecules. Has a
CC 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at
CC the 3' termini of nicked or gapped DNA molecules during short-patch
CC BER. Possesses a DNA 3' phosphodiesterase activity capable of removing
CC lesions (such as phosphoglycolate) blocking the 3' side of DNA strand
CC breaks. May also play a role in the epigenetic regulation of gene
CC expression by participating in DNA demethylation. Acts as a loading
CC factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-
CC terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB.
CC Plays a role in the protection from granzymes-mediated cellular repair
CC leading to cell death. Also involved in the DNA cleavage step of class
CC switch recombination (CSR). On the other hand, APEX1 also exerts
CC reversible 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; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Probably binds two magnesium or manganese ions per subunit.
CC {ECO:0000250};
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. {ECO:0000250}.
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. Binds to
CC CDK5. {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-(apurinic or apyrimidinic site)
CC endonuclease, mitochondrial]: Mitochondrion. Note=Translocation from
CC the cytoplasm to the mitochondria is mediated by ROS signaling and
CC cleavage mediated by granzyme A. Tom20-dependent translocated
CC mitochondrial APEX1 level is significantly increased after genotoxic
CC stress (By similarity). The cleaved APEX2 is only detected in
CC 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,
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}.
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}.
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}.
CC -!- PTM: Ubiquitinated by MDM2; leading to translocation to the cytoplasm
CC and proteasomal degradation. {ECO:0000250}.
CC -!- MISCELLANEOUS: The specific activity of the cleaved mitochondrial
CC endodeoxyribonuclease appeared 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}.
CC -!- SIMILARITY: Belongs to the DNA repair enzymes AP/ExoA family.
CC {ECO:0000305}.
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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 PDBsum; 7CD5; -.
DR PDBsum; 7CD6; -.
DR AlphaFoldDB; P28352; -.
DR SMR; P28352; -.
DR BioGRID; 198145; 17.
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; P28352; -.
DR PeptideAtlas; P28352; -.
DR PRIDE; P28352; -.
DR ProteomicsDB; 281828; -.
DR Antibodypedia; 62; 937 antibodies from 46 providers.
DR DNASU; 11792; -.
DR Ensembl; ENSMUST00000049411; ENSMUSP00000042602; ENSMUSG00000035960.
DR GeneID; 11792; -.
DR KEGG; mmu:11792; -.
DR UCSC; uc007tly.2; mouse.
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; 1105625at2759; -.
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; 10 hits in 112 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 298 other tissues.
DR ExpressionAtlas; P28352; baseline and differential.
DR Genevisible; P28352; MM.
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'-exodeoxyribonuclease 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' exodeoxyribonuclease 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:0004521; F:endoribonuclease activity; 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: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:0007568; P:aging; ISO:MGI.
DR GO; GO:0006284; P:base-excision repair; ISO:MGI.
DR GO; GO:0045454; P:cell redox homeostasis; IDA:MGI.
DR GO; GO:0071320; P:cellular response to cAMP; IEA:Ensembl.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:MGI.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IEA:Ensembl.
DR GO; GO:0000737; P:DNA catabolic process, endonucleolytic; 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:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0000723; P:telomere maintenance; ISO:MGI.
DR GO; GO:0097698; P:telomere maintenance via base-excision repair; ISO:MGI.
DR Gene3D; 3.60.10.10; -; 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 PANTHER; PTHR22748; PTHR22748; 1.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
DR TIGRFAMs; TIGR00633; xth; 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-(apurinic or apyrimidinic site) endonuclease"
FT /id="PRO_0000200011"
FT CHAIN 31..317
FT /note="DNA-(apurinic or apyrimidinic site) endonuclease,
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 (1-methyl-4-
FT phenylpyridinium). Loss of CDK5-mediated phosphorylation;
FT when associated with S-53."
FT /evidence="ECO:0000269|PubMed:20473298"
FT MUTAGEN 232
FT /note="T->E: Confers neuron sensitivity to MPP(+)/MPTP (1-
FT 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
