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Database: UniProt
Entry: P27695
LinkDB: P27695
Original site: P27695 
ID   APEX1_HUMAN             Reviewed;         318 AA.
AC   P27695; Q969L5; Q99775;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   19-MAR-2014, entry version 179.
DE   RecName: Full=DNA-(apurinic or apyrimidinic site) lyase;
DE            EC=3.1.-.-;
DE            EC=4.2.99.18;
DE   AltName: Full=APEX nuclease;
DE            Short=APEN;
DE   AltName: Full=Apurinic-apyrimidinic endonuclease 1;
DE            Short=AP endonuclease 1;
DE            Short=APE-1;
DE   AltName: Full=REF-1;
DE   AltName: Full=Redox factor-1;
DE   Contains:
DE     RecName: Full=DNA-(apurinic or apyrimidinic site) lyase, mitochondrial;
GN   Name=APEX1; Synonyms=APE, APE1, APEX, APX, HAP1, REF1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC   TISSUE=Melanocyte;
RX   PubMed=1719477; DOI=10.1093/nar/19.20.5519;
RA   Robson C.N., Hickson I.D.;
RT   "Isolation of cDNA clones encoding a human apurinic/apyrimidinic
RT   endonuclease that corrects DNA repair and mutagenesis defects in E.
RT   coli xth (exonuclease III) mutants.";
RL   Nucleic Acids Res. 19:5519-5523(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Placenta;
RX   PubMed=1722334; DOI=10.1073/pnas.88.24.11450;
RA   Demple B., Herman T., Chen D.S.;
RT   "Cloning and expression of APE, the cDNA encoding the major human
RT   apurinic endonuclease: definition of a family of DNA repair enzymes.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:11450-11454(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC   TISSUE=Bone marrow, and Leukocyte;
RX   PubMed=1627644; DOI=10.1016/0167-4781(92)90027-W;
RA   Seki S., Hatsushika M., Watanabe S., Akiyama K., Nagao K., Tsutsui K.;
RT   "cDNA cloning, sequencing, expression and possible domain structure of
RT   human APEX nuclease homologous to Escherichia coli exonuclease III.";
RL   Biochim. Biophys. Acta 1131:287-299(1992).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 2-21.
RX   PubMed=1380454;
RA   Xanthoudakis S., Miao G., Wang F., Pan Y.-C.E., Curran T.;
RT   "Redox activation of Fos-Jun DNA binding activity is mediated by a DNA
RT   repair enzyme.";
RL   EMBO J. 11:3323-3335(1992).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Carcinoma;
RX   PubMed=1371347; DOI=10.1093/nar/20.2.370;
RA   Cheng X.B., Bunville J., Patterson T.A.;
RT   "Nucleotide sequence of a cDNA for an apurinic/apyrimidinic
RT   endonuclease from HeLa cells.";
RL   Nucleic Acids Res. 20:370-370(1992).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Leukocyte;
RX   PubMed=1380694; DOI=10.1093/nar/20.15.4097;
RA   Zhao B., Grandy D.K., Hagerup J.M., Magenis R.E., Smith L.,
RA   Chauhan B.C., Henner W.D.;
RT   "The human gene for apurinic/apyrimidinic endonuclease (HAP1):
RT   sequence and localization to chromosome 14 band q12.";
RL   Nucleic Acids Res. 20:4097-4098(1992).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1383925; DOI=10.1093/nar/20.17.4417;
RA   Robson C.N., Hocchauser D., Craig R., Rack K., Buckle I.D.,
RA   Hickson I.D.;
RT   "Structure of the human DNA repair gene HAP1 and its localisation to
RT   chromosome 14q 11.2-12.";
RL   Nucleic Acids Res. 20:4417-4421(1992).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8086453; DOI=10.1016/0167-4781(94)90241-0;
RA   Akiyama K., Seki S., Oshida T., Yoshida M.;
RT   "Structure, promoter analysis and chromosomal assignment of the human
RT   APEX gene.";
RL   Biochim. Biophys. Acta 1219:15-25(1994).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=9110174;
RA   Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W.,
RA   Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A.;
RT   "Large-scale concatenation cDNA sequencing.";
RL   Genome Res. 7:353-358(1997).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT   vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [11]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-51; VAL-64 AND
RP   GLU-148.
RG   NIEHS SNPs program;
RL   Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN   [12]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12508121; DOI=10.1038/nature01348;
RA   Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA   Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA   Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S.,
RA   Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA   Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA   Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA   Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA   Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA   Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA   Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA   Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA   Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA   Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA   Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA   Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA   Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L.,
RA   Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA   Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA   Quetier F., Waterston R., Hood L., Weissenbach J.;
RT   "The DNA sequence and analysis of human chromosome 14.";
RL   Nature 421:601-607(2003).
RN   [13]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-148.
RC   TISSUE=Brain, Lung, and Skin;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [14]
RP   PROTEIN SEQUENCE OF 2-10, FUNCTION, INTERACTION WITH GZMA, CLEAVAGE BY
RP   GRANZYME A, IDENTIFICATION IN THE SET COMPLEX, MUTAGENESIS OF LYS-31;
RP   CYS-65 AND ASP-210, AND SUBCELLULAR LOCATION.
RX   PubMed=12524539; DOI=10.1038/ni885;
RA   Fan Z., Beresford P.J., Zhang D., Xu Z., Novina C.D., Yoshida A.,
RA   Pommier Y., Lieberman J.;
RT   "Cleaving the oxidative repair protein Ape1 enhances cell death
RT   mediated by granzyme A.";
RL   Nat. Immunol. 4:145-153(2003).
RN   [15]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-146.
RC   TISSUE=Placenta;
RX   PubMed=1284593; DOI=10.1093/hmg/1.9.677;
RA   Harrison L., Ascione G., Menninger J.C., Ward D.C., Demple B.;
RT   "Human apurinic endonuclease gene (APE): structure and genomic mapping
RT   (chromosome 14q11.2-12).";
RL   Hum. Mol. Genet. 1:677-680(1992).
RN   [16]
RP   FUNCTION, AND MUTAGENESIS OF CYS-65; CYS-93; CYS-99; CYS-138; CYS-208;
RP   CYS-296 AND CYS-310.
RX   PubMed=8355688;
RA   Walker L.J., Robson C.N., Black E., Gillespie D., Hickson I.D.;
RT   "Identification of residues in the human DNA repair enzyme HAP1 (Ref-
RT   1) that are essential for redox regulation of Jun DNA binding.";
RL   Mol. Cell. Biol. 13:5370-5376(1993).
RN   [17]
RP   FUNCTION, AND INTERACTION WITH XRCC5 AND XRCC6.
RX   PubMed=8621488; DOI=10.1074/jbc.271.15.8593;
RA   Chung U., Igarashi T., Nishishita T., Iwanari H., Iwamatsu A.,
RA   Suwa A., Mimori T., Hata K., Ebisu S., Ogata E., Fujita T.,
RA   Okazaki T.;
RT   "The interaction between Ku antigen and REF1 protein mediates negative
RT   gene regulation by extracellular calcium.";
RL   J. Biol. Chem. 271:8593-8598(1996).
RN   [18]
RP   FUNCTION, AND MUTAGENESIS OF ASN-212.
RX   PubMed=8932375; DOI=10.1093/nar/24.21.4217;
RA   Rothwell D.G., Hickson I.D.;
RT   "Asparagine 212 is essential for abasic site recognition by the human
RT   DNA repair endonuclease HAP1.";
RL   Nucleic Acids Res. 24:4217-4221(1996).
RN   [19]
RP   FUNCTION, SUBUNIT, INTERACTION WITH TXN, AND SUBCELLULAR LOCATION.
RX   PubMed=9108029; DOI=10.1073/pnas.94.8.3633;
RA   Hirota K., Matsui M., Iwata S., Nishiyama A., Mori K., Yodoi J.;
RT   "AP-1 transcriptional activity is regulated by a direct association
RT   between thioredoxin and Ref-1.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:3633-3638(1997).
RN   [20]
RP   FUNCTION, AND INTERACTION WITH POLB.
RX   PubMed=9207062; DOI=10.1073/pnas.94.14.7166;
RA   Bennett R.A., Wilson D.M. III, Wong D., Demple B.;
RT   "Interaction of human apurinic endonuclease and DNA polymerase beta in
RT   the base excision repair pathway.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:7166-7169(1997).
RN   [21]
RP   CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF ASP-283; ASP-308 AND
RP   HIS-309, AND COFACTOR.
RX   PubMed=9804799; DOI=10.1074/jbc.273.46.30360;
RA   Masuda Y., Bennett R.A., Demple B.;
RT   "Rapid dissociation of human apurinic endonuclease (Ape1) from incised
RT   DNA induced by magnesium.";
RL   J. Biol. Chem. 273:30360-30365(1998).
RN   [22]
RP   FUNCTION, INDUCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=9560228; DOI=10.1073/pnas.95.9.5061;
RA   Ramana C.V., Boldogh I., Izumi T., Mitra S.;
RT   "Activation of apurinic/apyrimidinic endonuclease in human cells by
RT   reactive oxygen species and its correlation with their adaptive
RT   response to genotoxicity of free radicals.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:5061-5066(1998).
RN   [23]
RP   FUNCTION, PHOSPHORYLATION BY CKII, AND SUBCELLULAR LOCATION.
RX   PubMed=10023679; DOI=10.1038/sj.onc.1202394;
RA   Fritz G., Kaina B.;
RT   "Phosphorylation of the DNA repair protein APE/REF-1 by CKII affects
RT   redox regulation of AP-1.";
RL   Oncogene 18:1033-1040(1999).
RN   [24]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=11118054;
RA   Wei S.J., Botero A., Hirota K., Bradbury C.M., Markovina S.,
RA   Laszlo A., Spitz D.R., Goswami P.C., Yodoi J., Gius D.;
RT   "Thioredoxin nuclear translocation and interaction with redox factor-1
RT   activates the activator protein-1 transcription factor in response to
RT   ionizing radiation.";
RL   Cancer Res. 60:6688-6695(2000).
RN   [25]
RP   FUNCTION, AND PHOSPHORYLATION BY PKC.
RX   PubMed=11452037; DOI=10.1093/nar/29.14.3116;
RA   Hsieh M.M., Hegde V., Kelley M.R., Deutsch W.A.;
RT   "Activation of APE/Ref-1 redox activity is mediated by reactive oxygen
RT   species and PKC phosphorylation.";
RL   Nucleic Acids Res. 29:3116-3122(2001).
RN   [26]
RP   FUNCTION.
RX   PubMed=11832948; DOI=10.1038/415655a;
RA   Chou K.M., Cheng Y.C.;
RT   "An exonucleolytic activity of human apurinic/apyrimidinic
RT   endonuclease on 3' mispaired DNA.";
RL   Nature 415:655-659(2002).
RN   [27]
RP   FUNCTION, AND INTERACTION WITH HNRNPL.
RX   PubMed=11809897; DOI=10.1093/nar/30.3.823;
RA   Kuninger D.T., Izumi T., Papaconstantinou J., Mitra S.;
RT   "Human AP-endonuclease 1 and hnRNP-L interact with a nCaRE-like
RT   repressor element in the AP-endonuclease 1 promoter.";
RL   Nucleic Acids Res. 30:823-829(2002).
RN   [28]
RP   INTERACTION WITH HDAC1; HDAC2 AND HDAC3, ACETYLATION AT LYS-6 AND
RP   LYS-7, AND MUTAGENESIS OF LYS-6 AND LYS-7.
RX   PubMed=14633989; DOI=10.1093/emboj/cdg595;
RA   Bhakat K.K., Izumi T., Yang S.H., Hazra T.K., Mitra S.;
RT   "Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation
RT   of the parathyroid hormone gene.";
RL   EMBO J. 22:6299-6309(2003).
RN   [29]
RP   CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF TYR-171.
RX   PubMed=15380100; DOI=10.1016/j.dnarep.2004.06.009;
RA   Mundle S.T., Fattal M.H., Melo L.F., Coriolan J.D., O'Regan N.E.,
RA   Strauss P.R.;
RT   "Novel role of tyrosine in catalysis by human AP endonuclease 1.";
RL   DNA Repair 3:1447-1455(2004).
RN   [30]
RP   INTERACTION WITH KPNA1 AND KPNA2, MUTAGENESIS OF LYS-6; LYS-7; GLU-12
RP   AND ASP-13, AND SUBCELLULAR LOCATION.
RX   PubMed=15942031; DOI=10.1093/nar/gki641;
RA   Jackson E.B., Theriot C.A., Chattopadhyay R., Mitra S., Izumi T.;
RT   "Analysis of nuclear transport signals in the human
RT   apurinic/apyrimidinic endonuclease (APE1/Ref1).";
RL   Nucleic Acids Res. 33:3303-3312(2005).
RN   [31]
RP   FUNCTION.
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   [32]
RP   SUBCELLULAR LOCATION.
RX   PubMed=17148573; DOI=10.1242/jcs.03312;
RA   Campalans A., Amouroux R., Bravard A., Epe B., Radicella J.P.;
RT   "UVA irradiation induces relocalisation of the DNA repair protein
RT   hOGG1 to nuclear speckles.";
RL   J. Cell Sci. 120:23-32(2007).
RN   [33]
RP   S-NITROSYLATION AT CYS-65; CYS-93 AND CYS-310 IN RESPONSE TO NITRIC
RP   OXIDE, AND SUBCELLULAR LOCATION.
RX   PubMed=17403694; DOI=10.1093/nar/gkl1163;
RA   Qu J., Liu G.H., Huang B., Chen C.;
RT   "Nitric oxide controls nuclear export of APE1/Ref-1 through S-
RT   nitrosation of cysteines 93 and 310.";
RL   Nucleic Acids Res. 35:2522-2532(2007).
RN   [34]
RP   FUNCTION.
RX   PubMed=18439621; DOI=10.1016/j.jmb.2008.03.053;
RA   Berquist B.R., McNeill D.R., Wilson D.M. III;
RT   "Characterization of abasic endonuclease activity of human Ape1 on
RT   alternative substrates, as well as effects of ATP and sequence context
RT   on AP site incision.";
RL   J. Mol. Biol. 379:17-27(2008).
RN   [35]
RP   FUNCTION, INTERACTION WITH MVP AND YBX1, MUTAGENESIS OF LYS-6 AND
RP   LYS-7, AND SUBCELLULAR LOCATION.
RX   PubMed=18809583; DOI=10.1128/MCB.00244-08;
RA   Chattopadhyay R., Das S., Maiti A.K., Boldogh I., Xie J., Hazra T.K.,
RA   Kohno K., Mitra S., Bhakat K.K.;
RT   "Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-1-
RT   mediated activation of the multidrug resistance gene MDR1.";
RL   Mol. Cell. Biol. 28:7066-7080(2008).
RN   [36]
RP   FUNCTION.
RX   PubMed=18179823; DOI=10.1016/j.molimm.2007.11.020;
RA   Guo Y., Chen J., Zhao T., Fan Z.;
RT   "Granzyme K degrades the redox/DNA repair enzyme Ape1 to trigger
RT   oxidative stress of target cells leading to cytotoxicity.";
RL   Mol. Immunol. 45:2225-2235(2008).
RN   [37]
RP   FUNCTION, AND MUTAGENESIS OF CYS-65; CYS-93; CYS-99; CYS-138; CYS-208;
RP   CYS-296 AND CYS-310.
RX   PubMed=18579163; DOI=10.1016/j.mrfmmm.2008.04.008;
RA   Georgiadis M.M., Luo M., Gaur R.K., Delaplane S., Li X., Kelley M.R.;
RT   "Evolution of the redox function in mammalian apurinic/apyrimidinic
RT   endonuclease.";
RL   Mutat. Res. 643:54-63(2008).
RN   [38]
RP   CATALYTIC ACTIVITY, COFACTOR, AND ENZYME MECHANISM.
RX   PubMed=19123919; DOI=10.1021/bi8016137;
RA   Mundle S.T., Delaney J.C., Essigmann J.M., Strauss P.R.;
RT   "Enzymatic mechanism of human apurinic/apyrimidinic endonuclease
RT   against a THF AP site model substrate.";
RL   Biochemistry 48:19-26(2009).
RN   [39]
RP   FUNCTION, INTERACTION WITH KRT8; NPM1; PRDX6; PRPF19; RPLP0 AND WDR77,
RP   RNA-BINDING, AND SUBCELLULAR LOCATION.
RX   PubMed=19188445; DOI=10.1128/MCB.01337-08;
RA   Vascotto C., Fantini D., Romanello M., Cesaratto L., Deganuto M.,
RA   Leonardi A., Radicella J.P., Kelley M.R., D'Ambrosio C., Scaloni A.,
RA   Quadrifoglio F., Tell G.;
RT   "APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in
RT   the rRNA quality control process.";
RL   Mol. Cell. Biol. 29:1834-1854(2009).
RN   [40]
RP   FUNCTION, RNA-BINDING, AND MUTAGENESIS OF GLU-96 AND HIS-309.
RX   PubMed=19401441; DOI=10.1093/nar/gkp275;
RA   Barnes T., Kim W.C., Mantha A.K., Kim S.E., Izumi T., Mitra S.,
RA   Lee C.H.;
RT   "Identification of apurinic/apyrimidinic endonuclease 1 (APE1) as the
RT   endoribonuclease that cleaves c-myc mRNA.";
RL   Nucleic Acids Res. 37:3946-3958(2009).
RN   [41]
RP   INTERACTION WITH MDM2, UBIQUITINATION, AND MUTAGENESIS OF LYS-24;
RP   LYS-25 AND LYS-27.
RX   PubMed=19219073; DOI=10.1038/onc.2009.5;
RA   Busso C.S., Iwakuma T., Izumi T.;
RT   "Ubiquitination of mammalian AP endonuclease (APE1) regulated by the
RT   p53-MDM2 signaling pathway.";
RL   Oncogene 28:1616-1625(2009).
RN   [42]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-197, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA   Walther T.C., Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [43]
RP   INTERACTION WITH TOMM20, MUTAGENESIS OF LYS-24; LYS-25; LYS-27;
RP   LYS-31; LYS-299; ARG-301 AND LYS-303, AND SUBCELLULAR LOCATION.
RX   PubMed=20231292; DOI=10.1074/jbc.M109.069591;
RA   Li M., Zhong Z., Zhu J., Xiang D., Dai N., Cao X., Qing Y., Yang Z.,
RA   Xie J., Li Z., Baugh L., Wang G., Wang D.;
RT   "Identification and characterization of mitochondrial targeting
RT   sequence of human apurinic/apyrimidinic endonuclease 1.";
RL   J. Biol. Chem. 285:14871-14881(2010).
RN   [44]
RP   FUNCTION, INTERACTION WITH SIRT1 AND XRCC1, MUTAGENESIS OF LYS-6 AND
RP   LYS-7, AND SUBCELLULAR LOCATION.
RX   PubMed=19934257; DOI=10.1093/nar/gkp1039;
RA   Yamamori T., DeRicco J., Naqvi A., Hoffman T.A., Mattagajasingh I.,
RA   Kasuno K., Jung S.B., Kim C.S., Irani K.;
RT   "SIRT1 deacetylates APE1 and regulates cellular base excision
RT   repair.";
RL   Nucleic Acids Res. 38:832-845(2010).
RN   [45]
RP   FUNCTION, INTERACTION WITH NPM1, RNA-BINDING, ACETYLATION AT LYS-27;
RP   LYS-31; LYS-32 AND LYS-35, MUTAGENESIS OF LYS-24; LYS-25; LYS-27;
RP   LYS-31 AND LYS-32, AND MASS SPECTROMETRY.
RX   PubMed=20699270; DOI=10.1093/nar/gkq691;
RA   Fantini D., Vascotto C., Marasco D., D'Ambrosio C., Romanello M.,
RA   Vitagliano L., Pedone C., Poletto M., Cesaratto L., Quadrifoglio F.,
RA   Scaloni A., Radicella J.P., Tell G.;
RT   "Critical lysine residues within the overlooked N-terminal domain of
RT   human APE1 regulate its biological functions.";
RL   Nucleic Acids Res. 38:8239-8256(2010).
RN   [46]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA   Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [47]
RP   FUNCTION IN DNA DEMETHYLATION.
RX   PubMed=21496894; DOI=10.1016/j.cell.2011.03.022;
RA   Guo J.U., Su Y., Zhong C., Ming G.L., Song H.;
RT   "Hydroxylation of 5-methylcytosine by TET1 promotes active DNA
RT   demethylation in the adult brain.";
RL   Cell 145:423-434(2011).
RN   [48]
RP   MUTAGENESIS OF ASN-68; ASP-70; TYR-171; PHE-266; ASP-283; ASP-308 AND
RP   HIS-309, CATALYTIC ACTIVITY, ACTIVE SITE, FUNCTION, AND COFACTOR.
RX   PubMed=21762700; DOI=10.1016/j.jmb.2011.06.050;
RA   Kim W.C., Berquist B.R., Chohan M., Uy C., Wilson D.M. III, Lee C.H.;
RT   "Characterization of the endoribonuclease active site of human
RT   apurinic/apyrimidinic endonuclease 1.";
RL   J. Mol. Biol. 411:960-971(2011).
RN   [49]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 32-318 IN COMPLEX WITH METAL
RP   IONS.
RX   PubMed=9351835; DOI=10.1093/emboj/16.21.6548;
RA   Gorman M.A., Morera S., Rothwell D.G., de La Fortelle E., Mol C.D.,
RA   Tainer J.A., Hickson I.D., Freemont P.S.;
RT   "The crystal structure of the human DNA repair endonuclease HAP1
RT   suggests the recognition of extra-helical deoxyribose at DNA abasic
RT   sites.";
RL   EMBO J. 16:6548-6558(1997).
RN   [50]
RP   X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 40-318 IN COMPLEX WITH DNA
RP   AND METAL ION, AND DNA-BINDING.
RX   PubMed=10667800; DOI=10.1038/35000249;
RA   Mol C.D., Izumi T., Mitra S., Tainer J.A.;
RT   "DNA-bound structures and mutants reveal abasic DNA binding by APE1
RT   and DNA repair coordination.";
RL   Nature 403:451-456(2000).
RN   [51]
RP   X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH METAL IONS,
RP   CATALYTIC ACTIVITY, AND COFACTOR.
RX   PubMed=11286553; DOI=10.1006/jmbi.2001.4529;
RA   Beernink P.T., Segelke B.W., Hadi M.Z., Erzberger J.P.,
RA   Wilson D.M. III, Rupp B.;
RT   "Two divalent metal ions in the active site of a new crystal form of
RT   human apurinic/apyrimidinic endonuclease, Ape1: implications for the
RT   catalytic mechanism.";
RL   J. Mol. Biol. 307:1023-1034(2001).
CC   -!- FUNCTION: Multifunctional protein that plays a central role in the
CC       cellular response to oxidative stress. The two major activities of
CC       APEX1 in DNA repair and redox regulation of transcriptional
CC       factors. Functions as a apurinic/apyrimidinic (AP)
CC       endodeoxyribonuclease in the DNA base excision repair (BER)
CC       pathway of DNA lesions induced by oxidative and alkylating agents.
CC       Initiates repair of AP sites in DNA by catalyzing hydrolytic
CC       incision of the phosphodiester backbone immediately adjacent to
CC       the damage, generating a single-strand break with 5'-deoxyribose
CC       phosphate and 3'-hydroxyl ends. Does also incise at AP sites in
CC       the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of
CC       R-loop structures, and single-stranded RNA molecules. Has a 3'-5'
CC       exoribonuclease activity on mismatched deoxyribonucleotides at the
CC       3' termini of nicked or gapped DNA molecules during short-patch
CC       BER. Possesses a DNA 3' phosphodiesterase activity capable of
CC       removing lesions (such as phosphoglycolate) blocking the 3' side
CC       of DNA strand breaks. May also play a role in the epigenetic
CC       regulation of gene expression by participating in DNA
CC       demethylation. Acts as a loading factor for POLB onto non-incised
CC       AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-
CC       phosphate (dRp) excision activity of POLB. Plays a role in the
CC       protection from granzymes-mediated cellular repair leading to cell
CC       death. Also involved in the DNA cleavage step of class switch
CC       recombination (CSR). On the other hand, APEX1 also exerts
CC       reversible nuclear redox activity to regulate DNA binding affinity
CC       and transcriptional activity of transcriptional factors by
CC       controlling the redox status of their DNA-binding domain, such as
CC       the FOS/JUN AP-1 complex after exposure to IR. Involved in
CC       calcium-dependent down-regulation of parathyroid hormone (PTH)
CC       expression by binding to negative calcium response elements
CC       (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6,
CC       associates with nCaRE, acting as an activator of transcriptional
CC       repression. Stimulates the YBX1-mediated MDR1 promoter activity,
CC       when acetylated at Lys-6 and Lys-7, leading to drug resistance.
CC       Acts also as an endoribonuclease involved in the control of
CC       single-stranded RNA metabolism. Plays a role in regulating MYC
CC       mRNA turnover by preferentially cleaving in between UA and CA
CC       dinucleotides of the MYC coding region determinant (CRD). In
CC       association with NMD1, plays a role in the rRNA quality control
CC       process during cell cycle progression. Associates, together with
CC       YBX1, on the MDR1 promoter. Together with NPM1, associates with
CC       rRNA. Binds DNA and RNA.
CC   -!- CATALYTIC ACTIVITY: The C-O-P bond 3' to the apurinic or
CC       apyrimidinic site in DNA is broken by a beta-elimination reaction,
CC       leaving a 3'-terminal unsaturated sugar and a product with a
CC       terminal 5'-phosphate.
CC   -!- COFACTOR: Magnesium. Can also utilize manganese. Probably binds
CC       two magnesium or manganese ions per subunit.
CC   -!- ENZYME REGULATION: NPM1 stimulates endodeoxyribonuclease activity
CC       on double-stranded DNA with AP sites, but inhibits
CC       endoribonuclease activity on single-stranded RNA containing AP
CC       sites.
CC   -!- SUBUNIT: Monomer. Homodimer; disulfide-linked. Component of the
CC       SET complex, composed at least of APEX1, GZMA, SET, ANP32A, HMGB2
CC       and NME1. Associates with the dimer XRCC5/XRCC6 in a DNA-dependent
CC       manner. Interacts with SIRT1; the interaction is increased in the
CC       context of genotoxic stress. Interacts with HDAC1, HDAC2 and
CC       HDAC3; the interactions are not dependent on the APEX1 acetylation
CC       status. Interacts with XRCC1; the interaction is induced by SIRT1
CC       and increased with the APEX1 acetylated form. Interacts with NPM1
CC       (via N-terminal domain); the interaction is RNA-dependent and
CC       decreases in hydrogen peroxide-damaged cells. Interacts (via N-
CC       terminus) with YBX1 (via C-terminus); the interaction is increased
CC       in presence of APEX1 acetylated at Lys-6 and Lys-7. Interacts with
CC       HNRNPL; the interaction is DNA-dependent. Interacts (via N-
CC       terminus) with KPNA1 and KPNA2. Interacts with TXN; the
CC       interaction stimulates the FOS/JUN AP-1 complex DNA-binding
CC       activity in a redox-dependent manner. Interacts with GZMA, KRT8,
CC       MDM2, POLB, PRDX6, PRPF19, RPLP0, TOMM20 and WDR77. Binds to CDK5
CC       (By similarity).
CC   -!- INTERACTION:
CC       Q09472:EP300; NbExp=8; IntAct=EBI-1048805, EBI-447295;
CC       Q96EB6:SIRT1; NbExp=6; IntAct=EBI-1048805, EBI-1802965;
CC   -!- SUBCELLULAR LOCATION: Nucleus. Nucleus, nucleolus. Nucleus
CC       speckle. Endoplasmic reticulum. Cytoplasm. Note=Detected in the
CC       cytoplasm of B-cells stimulated to switch (By similarity).
CC       Colocalized with SIRT1 in the nucleus. Colocalized with YBX1 in
CC       nuclear speckles after genotoxic stress. Together with OGG1 is
CC       recruited to nuclear speckles in UVA-irradiated cells. Colocalized
CC       with nucleolin and NPM1 in the nucleolus. Its nucleolar
CC       localization is cell cycle dependent and requires active rRNA
CC       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
CC       CRM1-dependent manner, possibly as a consequence of demasking a
CC       nuclear export signal (amino acid position 64-80). S-nitrosylation
CC       at Cys-93 and Cys-310 regulates its nuclear-cytosolic shuttling.
CC       Ubiquitinated form is localized predominantly in the cytoplasm.
CC   -!- SUBCELLULAR LOCATION: DNA-(apurinic or apyrimidinic site) lyase,
CC       mitochondrial: Mitochondrion. Note=The cleaved APEX2 is only
CC       detected in mitochondria (By similarity). Translocation from the
CC       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
CC       genotoxic stress.
CC   -!- INDUCTION: Up-regulated in presence of reactive oxygen species
CC       (ROS), like bleomycin, H(2)O(2) and phenazine methosulfate.
CC   -!- DOMAIN: The N-terminus contains the redox activity while the C-
CC       terminus exerts the DNA AP-endodeoxyribonuclease activity; both
CC       function are independent in their actions. An unconventional
CC       mitochondrial targeting sequence (MTS) is harbored within the C-
CC       terminus, that appears to be masked by the N-terminal sequence
CC       containing the nuclear localization signal (NLS), that probably
CC       blocks the interaction between the MTS and Tom proteins.
CC   -!- PTM: Phosphorylated. Phosphorylation by kinase PKC or casein
CC       kinase CK2 results in enhanced redox activity that stimulates
CC       binding of the FOS/JUN AP-1 complex to its cognate binding site.
CC       AP-endodeoxyribonuclease activity is not affected by CK2-mediated
CC       phosphorylation. Phosphorylation of Thr-233 by CDK5 reduces AP-
CC       endodeoxyribonuclease activity resulting in accumulation of DNA
CC       damage and contributing to neuronal death.
CC   -!- PTM: Acetylated on Lys-6 and Lys-7. Acetylation is increased by
CC       the transcriptional coactivator EP300 acetyltransferase, genotoxic
CC       agents like H(2)O(2) and methyl methanesulfonate (MMS).
CC       Acetylation increases its binding affinity to the negative calcium
CC       response element (nCaRE) DNA promoter. The acetylated form induces
CC       a stronger binding of YBX1 to the Y-box sequence in the MDR1
CC       promoter than the unacetylated form. Deacetylated on lysines. Lys-
CC       6 and Lys-7 are deacetylated by SIRT1.
CC   -!- PTM: Cleaved at Lys-31 by granzyme A to create the mitochondrial
CC       form; leading in reduction of binding to DNA, AP endodeoxynuclease
CC       activity, redox activation of transcription factors and to
CC       enhanced cell death. Cleaved by granzyme K; leading to
CC       intracellular ROS accumulation and enhanced cell death after
CC       oxidative stress.
CC   -!- PTM: Cys-65 and Cys-93 are nitrosylated in response to nitric
CC       oxide (NO) and lead to the exposure of the nuclear export signal
CC       (NES).
CC   -!- PTM: Ubiquitinated by MDM2; leading to translocation to the
CC       cytoplasm and proteasomal degradation.
CC   -!- MISCELLANEOUS: Extract of mitochondria, but not of nuclei or
CC       cytosol, cleaves recombinant APEX1 to generate a mitochondrial
CC       APEX1-sized product (By similarity). The specific activity of the
CC       cleaved mitochondrial endodeoxyribonuclease appeared to be about
CC       3-fold higher than that of the full-length form.
CC   -!- SIMILARITY: Belongs to the DNA repair enzymes AP/ExoA family.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/apex/";
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DR   EMBL; X59764; CAA42437.1; -; mRNA.
DR   EMBL; M80261; AAA58371.1; -; mRNA.
DR   EMBL; D90373; BAA14381.1; -; mRNA.
DR   EMBL; S43127; AAB22977.1; -; mRNA.
DR   EMBL; M81955; AAA58372.1; -; mRNA.
DR   EMBL; M92444; AAA58629.1; -; Genomic_DNA.
DR   EMBL; X66133; CAA46925.1; -; Genomic_DNA.
DR   EMBL; D13370; BAA02633.1; -; Genomic_DNA.
DR   EMBL; U79268; AAB50212.1; -; mRNA.
DR   EMBL; BT007236; AAP35900.1; -; mRNA.
DR   EMBL; AF488551; AAL86909.1; -; Genomic_DNA.
DR   EMBL; AL355075; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC002338; AAH02338.1; -; mRNA.
DR   EMBL; BC004979; AAH04979.1; -; mRNA.
DR   EMBL; BC008145; AAH08145.1; -; mRNA.
DR   EMBL; BC019291; AAH19291.1; -; mRNA.
DR   EMBL; M99703; AAA58373.1; -; Genomic_DNA.
DR   PIR; S23550; S23550.
DR   RefSeq; NP_001231178.1; NM_001244249.1.
DR   RefSeq; NP_001632.2; NM_001641.3.
DR   RefSeq; NP_542379.1; NM_080648.2.
DR   RefSeq; NP_542380.1; NM_080649.2.
DR   RefSeq; XP_005267638.1; XM_005267581.1.
DR   UniGene; Hs.73722; -.
DR   PDB; 1BIX; X-ray; 2.20 A; A=32-318.
DR   PDB; 1CQG; NMR; -; B=59-71.
DR   PDB; 1CQH; NMR; -; B=59-71.
DR   PDB; 1DE8; X-ray; 2.95 A; A/B=43-318.
DR   PDB; 1DE9; X-ray; 3.00 A; A/B=43-318.
DR   PDB; 1DEW; X-ray; 2.65 A; A/B=40-318.
DR   PDB; 1E9N; X-ray; 2.20 A; A/B=1-318.
DR   PDB; 1HD7; X-ray; 1.95 A; A=1-318.
DR   PDB; 2ISI; X-ray; 2.76 A; A/B/C=2-317.
DR   PDB; 2O3H; X-ray; 1.90 A; A=40-318.
DR   PDB; 3U8U; X-ray; 2.15 A; A/B/C/D/E/F=1-318.
DR   PDB; 4IEM; X-ray; 2.39 A; A/B/C/D=2-318.
DR   PDB; 4LND; X-ray; 1.92 A; A/B/C=39-318.
DR   PDBsum; 1BIX; -.
DR   PDBsum; 1CQG; -.
DR   PDBsum; 1CQH; -.
DR   PDBsum; 1DE8; -.
DR   PDBsum; 1DE9; -.
DR   PDBsum; 1DEW; -.
DR   PDBsum; 1E9N; -.
DR   PDBsum; 1HD7; -.
DR   PDBsum; 2ISI; -.
DR   PDBsum; 2O3H; -.
DR   PDBsum; 3U8U; -.
DR   PDBsum; 4IEM; -.
DR   PDBsum; 4LND; -.
DR   DisProt; DP00007; -.
DR   ProteinModelPortal; P27695; -.
DR   SMR; P27695; 44-318.
DR   BioGrid; 106825; 63.
DR   DIP; DIP-6130N; -.
DR   IntAct; P27695; 29.
DR   MINT; MINT-119189; -.
DR   STRING; 9606.ENSP00000216714; -.
DR   BindingDB; P27695; -.
DR   ChEMBL; CHEMBL5619; -.
DR   DrugBank; DB04967; Lucanthone.
DR   PhosphoSite; P27695; -.
DR   DMDM; 113984; -.
DR   PaxDb; P27695; -.
DR   PeptideAtlas; P27695; -.
DR   PRIDE; P27695; -.
DR   DNASU; 328; -.
DR   Ensembl; ENST00000216714; ENSP00000216714; ENSG00000100823.
DR   Ensembl; ENST00000398030; ENSP00000381111; ENSG00000100823.
DR   Ensembl; ENST00000555414; ENSP00000451979; ENSG00000100823.
DR   Ensembl; ENST00000557344; ENSP00000452137; ENSG00000100823.
DR   GeneID; 328; -.
DR   KEGG; hsa:328; -.
DR   UCSC; uc001vxg.3; human.
DR   CTD; 328; -.
DR   GeneCards; GC14P020924; -.
DR   HGNC; HGNC:587; APEX1.
DR   HPA; CAB004294; -.
DR   HPA; CAB047307; -.
DR   HPA; HPA000956; -.
DR   HPA; HPA002564; -.
DR   MIM; 107748; gene.
DR   neXtProt; NX_P27695; -.
DR   PharmGKB; PA201059; -.
DR   eggNOG; COG0708; -.
DR   HOGENOM; HOG000034586; -.
DR   HOVERGEN; HBG050531; -.
DR   InParanoid; P27695; -.
DR   KO; K10771; -.
DR   OMA; HETKFPA; -.
DR   OrthoDB; EOG7C8GJ6; -.
DR   PhylomeDB; P27695; -.
DR   TreeFam; TF315048; -.
DR   BRENDA; 4.2.99.18; 2681.
DR   Reactome; REACT_216; DNA Repair.
DR   ChiTaRS; APEX1; human.
DR   EvolutionaryTrace; P27695; -.
DR   GeneWiki; APEX1; -.
DR   GenomeRNAi; 328; -.
DR   NextBio; 1347; -.
DR   PMAP-CutDB; P27695; -.
DR   PRO; PR:P27695; -.
DR   ArrayExpress; P27695; -.
DR   Bgee; P27695; -.
DR   CleanEx; HS_APEX1; -.
DR   CleanEx; HS_HAP1; -.
DR   Genevestigator; P27695; -.
DR   GO; GO:0005813; C:centrosome; IDA:HPA.
DR   GO; GO:0005783; C:endoplasmic reticulum; TAS:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR   GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005840; C:ribosome; TAS:UniProtKB.
DR   GO; GO:0005667; C:transcription factor complex; IEA:Ensembl.
DR   GO; GO:0008408; F:3'-5' exonuclease activity; IDA:UniProtKB.
DR   GO; GO:0031490; F:chromatin DNA binding; IDA:UniProtKB.
DR   GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB.
DR   GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) lyase activity; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IDA:UniProtKB.
DR   GO; GO:0016491; F:oxidoreductase activity; IDA:UniProtKB.
DR   GO; GO:0004528; F:phosphodiesterase I activity; TAS:UniProtKB.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0004523; F:RNA-DNA hybrid ribonuclease activity; TAS:UniProtKB.
DR   GO; GO:0016890; F:site-specific endodeoxyribonuclease activity, specific for altered base; IDA:UniProtKB.
DR   GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR   GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc.
DR   GO; GO:0004844; F:uracil DNA N-glycosylase activity; TAS:ProtInc.
DR   GO; GO:0007568; P:aging; IEA:Ensembl.
DR   GO; GO:0006284; P:base-excision repair; TAS:Reactome.
DR   GO; GO:0045454; P:cell redox homeostasis; IEA:Ensembl.
DR   GO; GO:0071320; P:cellular response to cAMP; IEA:Ensembl.
DR   GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl.
DR   GO; GO:0071375; P:cellular response to peptide hormone stimulus; IEA:Ensembl.
DR   GO; GO:0080111; P:DNA demethylation; IDA:UniProtKB.
DR   GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR   GO; GO:0014912; P:negative regulation of smooth muscle cell migration; IEA:Ensembl.
DR   GO; GO:0045739; P:positive regulation of DNA repair; IDA:UniProtKB.
DR   GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR   GO; GO:0043488; P:regulation of mRNA stability; IMP:UniProtKB.
DR   GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-KW.
DR   GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR   GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
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; 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;
KW   Cleavage on pair of basic residues; Complete proteome; Cytoplasm;
KW   Direct protein sequencing; Disulfide bond; DNA damage;
KW   DNA recombination; DNA repair; DNA-binding; Endonuclease;
KW   Endoplasmic reticulum; Exonuclease; Hydrolase; Lyase; Magnesium;
KW   Metal-binding; Mitochondrion; Nuclease; Nucleus; Phosphoprotein;
KW   Polymorphism; Reference proteome; Repressor; RNA-binding;
KW   S-nitrosylation; Transcription; Transcription regulation;
KW   Ubl conjugation.
FT   INIT_MET      1      1       Removed.
FT   CHAIN         2    318       DNA-(apurinic or apyrimidinic site)
FT                                lyase.
FT                                /FTId=PRO_0000200010.
FT   CHAIN        32    318       DNA-(apurinic or apyrimidinic site)
FT                                lyase, mitochondrial (By similarity).
FT                                /FTId=PRO_0000402572.
FT   REGION        2     33       Necessary for interaction with YBX1,
FT                                binding to RNA, NPM1-dependent
FT                                association with rRNA, endoribonuclease
FT                                activity on abasic RNA and localization
FT                                in the nucleoli.
FT   REGION        8     13       Nuclear localization signal (NLS).
FT   REGION       23     33       Necessary for interaction with NPM1 and
FT                                for efficient rRNA binding.
FT   REGION       64     80       Nuclear export signal (NES).
FT   REGION      289    318       Mitochondrial targeting sequence (MTS).
FT   ACT_SITE    171    171
FT   ACT_SITE    210    210       Proton donor/acceptor.
FT   METAL        70     70       Magnesium 1.
FT   METAL        96     96       Magnesium 1.
FT   METAL       210    210       Magnesium 2.
FT   METAL       212    212       Magnesium 2.
FT   METAL       308    308       Magnesium 1.
FT   SITE         31     32       Cleavage; by granzyme A.
FT   SITE        212    212       Transition state stabilizer.
FT   SITE        283    283       Important for catalytic activity.
FT   SITE        309    309       Interaction with DNA substrate.
FT   MOD_RES       6      6       N6-acetyllysine; by EP300.
FT   MOD_RES       7      7       N6-acetyllysine; by EP300.
FT   MOD_RES      27     27       N6-acetyllysine.
FT   MOD_RES      31     31       N6-acetyllysine.
FT   MOD_RES      32     32       N6-acetyllysine.
FT   MOD_RES      35     35       N6-acetyllysine.
FT   MOD_RES      65     65       S-nitrosocysteine; alternate.
FT   MOD_RES      93     93       S-nitrosocysteine; alternate.
FT   MOD_RES     197    197       N6-acetyllysine.
FT   MOD_RES     233    233       Phosphothreonine; by CDK5 (By
FT                                similarity).
FT   MOD_RES     310    310       S-nitrosocysteine.
FT   DISULFID     65     93       Alternate (Probable).
FT   VARIANT      51     51       Q -> H (in dbSNP:rs1048945).
FT                                /FTId=VAR_013455.
FT   VARIANT      64     64       I -> V (in dbSNP:rs2307486).
FT                                /FTId=VAR_014823.
FT   VARIANT     148    148       D -> E (in dbSNP:rs1130409).
FT                                /FTId=VAR_019790.
FT   MUTAGEN       6      6       K->R: Lack of acetylation, does not
FT                                stimulate the YBX1-mediated MDR1 promoter
FT                                activity and alter nuclear subcellular
FT                                localization; when associated with R-7.
FT                                Does not inhibit interaction with HDAC1,
FT                                HDAC2 and HDAC3. Absence of increase in
FT                                nCaRE binding activity.
FT   MUTAGEN       7      7       K->R: Lack of acetylation and does not
FT                                stimulate the YBX1-mediated MDR1 promoter
FT                                activity and alter nuclear subcellular
FT                                localization; when associated with R-6.
FT   MUTAGEN      12     12       E->A: Reduces nuclear localization; when
FT                                associated with A-13.
FT   MUTAGEN      13     13       D->A: Reduces nuclear localization; when
FT                                associated with A-12.
FT   MUTAGEN      24     24       K->A: Enhances the interaction with
FT                                TOMM20. Inhibits rRNA binding,
FT                                interaction with NPM1, nuclear
FT                                localization and modulates its
FT                                endodeoxyribonuclease activity; when
FT                                associated with A-25; A-27; A-31 and A-
FT                                32. Inhibits ubiquitination; when
FT                                associated with K-25 and K-27.
FT   MUTAGEN      25     25       K->A: Enhances the interaction with
FT                                TOMM20. Inhibits rRNA binding,
FT                                interaction with NPM1, nuclear
FT                                localization and modulates its
FT                                endodeoxyribonuclease activity; when
FT                                associated with A-24; A-27; A-31 and A-
FT                                32. Inhibits ubiquitination; when
FT                                associated with K-24 and K-27.
FT   MUTAGEN      27     27       K->A: Enhances the interaction with
FT                                TOMM20. Inhibits rRNA binding,
FT                                interaction with NPM1, nuclear
FT                                localization and modulates its
FT                                endodeoyribonuclease activity; when
FT                                associated with A-24; A-25; A-31 and A-
FT                                32. Inhibits ubiquitination; when
FT                                associated with K-24 and K-25.
FT   MUTAGEN      31     31       K->A: Enhances the interaction with
FT                                TOMM20. Does not inhibit redox and AP
FT                                endodeoyribonuclease activities. Inhibits
FT                                rRNA binding, interaction with NPM1,
FT                                nuclear localization and modulates its
FT                                endodeoxyribonuclease activity; when
FT                                associated with A-24; A-25; A-27 and A-
FT                                32. Reduces protection from granzyme A-
FT                                mediated cell death; when associated with
FT                                A-65 and A-210.
FT   MUTAGEN      32     32       K->A: Inhibits rRNA binding, interaction
FT                                with NPM1, nuclear localization and
FT                                modulates its endodeoxyribonuclease
FT                                activity; when associated with A-24; A-
FT                                25; A-27 and A-31.
FT   MUTAGEN      65     65       C->A: Abolishes the redox activity. Does
FT                                not abolish the AP endodeoxyribonuclease
FT                                and phosphodiesterase activities. Reduces
FT                                protection from granzyme A-mediated cell
FT                                death; when associated with A-31 and A-
FT                                210.
FT   MUTAGEN      65     65       C->S: Does not abolish NO-induced
FT                                nitrosylation. Enhances NO-induced
FT                                nuclear export.
FT   MUTAGEN      68     68       N->A: Nearly abolishes AP
FT                                endodeoxyribonuclease activity.
FT   MUTAGEN      70     70       D->A: Strongly reduces AP
FT                                endodeoxyribonuclease activity.
FT   MUTAGEN      93     93       C->A: Abolishes partially the redox
FT                                activity.
FT   MUTAGEN      93     93       C->S: Does not abolish NO-induced
FT                                nitrosylation. Abolishes NO-induced
FT                                nitrosylation and translocation from the
FT                                nucleus to the cytoplasm; when associated
FT                                with S-310.
FT   MUTAGEN      96     96       E->A: Lacks MYC CRD RNA cleavage
FT                                activity.
FT   MUTAGEN      99     99       C->A: Does not abolish the redox
FT                                activity.
FT   MUTAGEN     138    138       C->A: Does not abolish the redox
FT                                activity.
FT   MUTAGEN     171    171       Y->A,F,H: Abolishes the AP
FT                                endodeoxyribonuclease activity.
FT   MUTAGEN     208    208       C->A: Does not abolish the redox
FT                                activity.
FT   MUTAGEN     210    210       D->A,N: Abolishes the AP
FT                                endodeoxyribonuclease activity. Reduces
FT                                protection from granzyme A-mediated cell
FT                                death; when associated with A-31 and A-
FT                                65.
FT   MUTAGEN     212    212       N->A: Abolishes AP endodeoxyribonuclease
FT                                activity.
FT   MUTAGEN     212    212       N->Q,D: Decreases AP
FT                                endodeoxyribonuclease activity.
FT   MUTAGEN     266    266       F->A: Strongly reduces AP
FT                                endodeoxyribonuclease activity.
FT   MUTAGEN     283    283       D->A: Strongly reduces AP
FT                                endodeoxyribonuclease activity, but does
FT                                not affect RNA cleavage activity. Nearly
FT                                abolishes AP endodeoxyribonuclease
FT                                activity; when associated with A-308.
FT   MUTAGEN     296    296       C->A: Does not abolish the redox
FT                                activity.
FT   MUTAGEN     299    299       K->A: Reduces the interaction with
FT                                TOMM20. Abolishes localization in the
FT                                mitochondria; when associated with A-301.
FT   MUTAGEN     301    301       R->A: Reduces the interaction with
FT                                TOMM20. Abolishes localization in the
FT                                mitochondria; when associated with A-299.
FT   MUTAGEN     303    303       K->A: Reduces the interaction with
FT                                TOMM20.
FT   MUTAGEN     308    308       D->A: Reduces AP endodeoxyribonuclease
FT                                activity. Nearly abolishes AP
FT                                endodeoxyribonuclease activity; when
FT                                associated with A-283.
FT   MUTAGEN     309    309       H->N,S: Abolishes AP
FT                                endodeoxyribonuclease activity. Lacks MYC
FT                                CRD RNA cleavage activity.
FT   MUTAGEN     310    310       C->A: Does not abolish the redox
FT                                activity.
FT   MUTAGEN     310    310       C->S: Does not abolish NO-induced
FT                                nitrosylation. Abolishes NO-induced
FT                                nitrosylation and translocation from the
FT                                nucleus to the cytoplasm; when associated
FT                                with S-93.
FT   CONFLICT     57     57       G -> A (in Ref. 2; AAA58371).
FT   CONFLICT    306    306       G -> A (in Ref. 2; AAA58371).
FT   STRAND       62     68
FT   HELIX        72     77
FT   HELIX        80     87
FT   STRAND       90     95
FT   HELIX       101    103
FT   HELIX       106    110
FT   HELIX       112    114
FT   STRAND      116    120
FT   STRAND      122    124
FT   STRAND      126    128
FT   STRAND      131    137
FT   STRAND      140    145
FT   HELIX       149    151
FT   STRAND      152    154
FT   STRAND      157    161
FT   STRAND      166    171
FT   HELIX       177    179
FT   HELIX       182    200
FT   STRAND      205    210
FT   HELIX       217    219
FT   TURN        223    225
FT   STRAND      227    229
FT   TURN        230    232
FT   HELIX       234    246
FT   STRAND      249    251
FT   HELIX       252    256
FT   STRAND      257    259
FT   HELIX       270    272
FT   HELIX       273    276
FT   STRAND      283    287
FT   HELIX       289    294
FT   STRAND      295    300
FT   STRAND      306    309
FT   STRAND      312    316
SQ   SEQUENCE   318 AA;  35555 MW;  B88579C01BAF80C6 CRC64;
     MPKRGKKGAV AEDGDELRTE PEAKKSKTAA KKNDKEAAGE GPALYEDPPD QKTSPSGKPA
     TLKICSWNVD GLRAWIKKKG LDWVKEEAPD ILCLQETKCS ENKLPAELQE LPGLSHQYWS
     APSDKEGYSG VGLLSRQCPL KVSYGIGDEE HDQEGRVIVA EFDSFVLVTA YVPNAGRGLV
     RLEYRQRWDE AFRKFLKGLA SRKPLVLCGD LNVAHEEIDL RNPKGNKKNA GFTPQERQGF
     GELLQAVPLA DSFRHLYPNT PYAYTFWTYM MNARSKNVGW RLDYFLLSHS LLPALCDSKI
     RSKALGSDHC PITLYLAL
//
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