APEX1_HUMAN
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 03-AUG-2022, entry version 252.
DE RecName: Full=DNA-(apurinic or apyrimidinic site) endonuclease;
DE EC=3.1.11.2 {ECO:0000269|PubMed:11286553, ECO:0000269|PubMed:15380100, ECO:0000269|PubMed:19123919, ECO:0000269|PubMed:21762700, ECO:0000269|PubMed:9804799};
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) endonuclease, mitochondrial;
GN Name=APEX1; Synonyms=APE, APE1, APEX, APX, HAP1, REF1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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. coli
RT 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 apurinic
RT 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; DOI=10.1002/j.1460-2075.1992.tb05411.x;
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 endonuclease
RT 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., Chauhan B.C.,
RA Henner W.D.;
RT "The human gene for apurinic/apyrimidinic endonuclease (HAP1): sequence and
RT 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., 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 APEX
RT gene.";
RL Biochim. Biophys. Acta 1219:15-25(1994).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=9110174; DOI=10.1101/gr.7.4.353;
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 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 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., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., 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., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA 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 project:
RT 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 mediated by
RT 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; DOI=10.1128/mcb.13.9.5370-5376.1993;
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-1)
RT 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., Suwa A.,
RA Mimori T., Hata K., Ebisu S., Ogata E., Fujita T., Okazaki T.;
RT "The interaction between Ku antigen and REF1 protein mediates negative gene
RT 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 DNA
RT 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 between
RT 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 the
RT 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 HIS-309,
RP 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 DNA
RT 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 response to
RT 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 redox
RT 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., Laszlo A.,
RA 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 IDENTIFICATION IN THE SET COMPLEX.
RX PubMed=11909973; DOI=10.1128/mcb.22.8.2810-2820.2002;
RA Fan Z., Beresford P.J., Zhang D., Lieberman J.;
RT "HMG2 interacts with the nucleosome assembly protein SET and is a target of
RT the cytotoxic T-lymphocyte protease granzyme A.";
RL Mol. Cell. Biol. 22:2810-2820(2002).
RN [27]
RP FUNCTION.
RX PubMed=11832948; DOI=10.1038/415655a;
RA Chou K.M., Cheng Y.C.;
RT "An exonucleolytic activity of human apurinic/apyrimidinic endonuclease on
RT 3' mispaired DNA.";
RL Nature 415:655-659(2002).
RN [28]
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 repressor
RT element in the AP-endonuclease 1 promoter.";
RL Nucleic Acids Res. 30:823-829(2002).
RN [29]
RP INTERACTION WITH HDAC1; HDAC2 AND HDAC3, ACETYLATION AT LYS-6 AND LYS-7,
RP 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 of the
RT parathyroid hormone gene.";
RL EMBO J. 22:6299-6309(2003).
RN [30]
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 [31]
RP INTERACTION WITH KPNA1 AND KPNA2, MUTAGENESIS OF LYS-6; LYS-7; GLU-12 AND
RP 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 apurinic/apyrimidinic
RT endonuclease (APE1/Ref1).";
RL Nucleic Acids Res. 33:3303-3312(2005).
RN [32]
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 [33]
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 hOGG1 to
RT nuclear speckles.";
RL J. Cell Sci. 120:23-32(2007).
RN [34]
RP S-NITROSYLATION AT CYS-65; CYS-93 AND CYS-310 IN RESPONSE TO NITRIC OXIDE,
RP 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-nitrosation
RT of cysteines 93 and 310.";
RL Nucleic Acids Res. 35:2522-2532(2007).
RN [35]
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 on
RT AP site incision.";
RL J. Mol. Biol. 379:17-27(2008).
RN [36]
RP FUNCTION, INTERACTION WITH MVP AND YBX1, MUTAGENESIS OF LYS-6 AND LYS-7,
RP 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-mediated
RT activation of the multidrug resistance gene MDR1.";
RL Mol. Cell. Biol. 28:7066-7080(2008).
RN [37]
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 oxidative
RT stress of target cells leading to cytotoxicity.";
RL Mol. Immunol. 45:2225-2235(2008).
RN [38]
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 [39]
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 against a
RT THF AP site model substrate.";
RL Biochemistry 48:19-26(2009).
RN [40]
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 the
RT rRNA quality control process.";
RL Mol. Cell. Biol. 29:1834-1854(2009).
RN [41]
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., 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 [42]
RP INTERACTION WITH MDM2, UBIQUITINATION, AND MUTAGENESIS OF LYS-24; LYS-25
RP 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 p53-
RT MDM2 signaling pathway.";
RL Oncogene 28:1616-1625(2009).
RN [43]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-197, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA 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 [44]
RP INTERACTION WITH TOMM20, MUTAGENESIS OF LYS-24; LYS-25; LYS-27; LYS-31;
RP 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 sequence of
RT human apurinic/apyrimidinic endonuclease 1.";
RL J. Biol. Chem. 285:14871-14881(2010).
RN [45]
RP FUNCTION, INTERACTION WITH SIRT1 AND XRCC1, MUTAGENESIS OF LYS-6 AND LYS-7,
RP 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 repair.";
RL Nucleic Acids Res. 38:832-845(2010).
RN [46]
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; LYS-31
RP AND LYS-32, AND IDENTIFICATION BY 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 human
RT APE1 regulate its biological functions.";
RL Nucleic Acids Res. 38:8239-8256(2010).
RN [47]
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., Buerckstuemmer T.,
RA 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 [48]
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 [49]
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 [50]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [51]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [52]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [53]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 32-318 IN COMPLEX WITH METAL 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 suggests
RT the recognition of extra-helical deoxyribose at DNA abasic sites.";
RL EMBO J. 16:6548-6558(1997).
RN [54]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 40-318 IN COMPLEX WITH DNA AND
RP 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 and DNA
RT repair coordination.";
RL Nature 403:451-456(2000).
RN [55]
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., Wilson D.M. III,
RA Rupp B.;
RT "Two divalent metal ions in the active site of a new crystal form of human
RT apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic
RT 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 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:10023679, ECO:0000269|PubMed:11118054,
CC ECO:0000269|PubMed:11452037, ECO:0000269|PubMed:11809897,
CC ECO:0000269|PubMed:11832948, ECO:0000269|PubMed:12524539,
CC ECO:0000269|PubMed:16617147, ECO:0000269|PubMed:1719477,
CC ECO:0000269|PubMed:18179823, ECO:0000269|PubMed:18439621,
CC ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:18809583,
CC ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:19401441,
CC ECO:0000269|PubMed:19934257, ECO:0000269|PubMed:20699270,
CC ECO:0000269|PubMed:21496894, ECO:0000269|PubMed:21762700,
CC ECO:0000269|PubMed:8355688, ECO:0000269|PubMed:8621488,
CC ECO:0000269|PubMed:8932375, ECO:0000269|PubMed:9108029,
CC ECO:0000269|PubMed:9207062, ECO:0000269|PubMed:9560228,
CC ECO:0000269|PubMed:9804799}.
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:0000269|PubMed:11286553, ECO:0000269|PubMed:15380100,
CC ECO:0000269|PubMed:19123919, ECO:0000269|PubMed:21762700,
CC ECO:0000269|PubMed:9804799};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11286553, ECO:0000269|PubMed:19123919,
CC ECO:0000269|PubMed:21762700, ECO:0000269|PubMed:9804799};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:11286553, ECO:0000269|PubMed:19123919,
CC ECO:0000269|PubMed:21762700, ECO:0000269|PubMed:9804799};
CC Note=Probably binds two magnesium or manganese ions per subunit.
CC {ECO:0000269|PubMed:11286553, ECO:0000269|PubMed:19123919,
CC ECO:0000269|PubMed:21762700, ECO:0000269|PubMed:9804799};
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 -!- 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:10667800, ECO:0000269|PubMed:11286553,
CC ECO:0000269|PubMed:11809897, ECO:0000269|PubMed:11909973,
CC ECO:0000269|PubMed:12524539, ECO:0000269|PubMed:14633989,
CC ECO:0000269|PubMed:15942031, ECO:0000269|PubMed:18809583,
CC ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:19219073,
CC ECO:0000269|PubMed:19934257, ECO:0000269|PubMed:20231292,
CC ECO:0000269|PubMed:20699270, ECO:0000269|PubMed:8621488,
CC ECO:0000269|PubMed:9108029, ECO:0000269|PubMed:9207062,
CC ECO:0000269|PubMed:9351835}.
CC -!- INTERACTION:
CC P27695; Q09472: EP300; NbExp=8; IntAct=EBI-1048805, EBI-447295;
CC P27695; Q16236: NFE2L2; NbExp=3; IntAct=EBI-1048805, EBI-2007911;
CC P27695; Q96EB6: SIRT1; NbExp=6; IntAct=EBI-1048805, EBI-1802965;
CC P27695; O88846: Rnf4; Xeno; NbExp=2; IntAct=EBI-1048805, EBI-7258907;
CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus, nucleolus. Nucleus speckle.
CC Endoplasmic reticulum. Cytoplasm. Note=Detected in the cytoplasm of B-
CC cells stimulated to switch (By similarity). Colocalized with SIRT1 in
CC the 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 64-80). S-nitrosylation at Cys-93
CC and Cys-310 regulates its nuclear-cytosolic shuttling. Ubiquitinated
CC form is localized predominantly in the cytoplasm. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [DNA-(apurinic or apyrimidinic site)
CC endonuclease, mitochondrial]: Mitochondrion. Note=The cleaved APEX2 is
CC only detected in mitochondria (By similarity). Translocation from the
CC cytoplasm to the mitochondria is mediated by ROS signaling and cleavage
CC mediated by granzyme A. Tom20-dependent translocated mitochondrial
CC APEX1 level is significantly increased after genotoxic stress.
CC {ECO:0000250}.
CC -!- INDUCTION: Up-regulated in presence of reactive oxygen species (ROS),
CC like bleomycin, H(2)O(2) and phenazine methosulfate.
CC {ECO:0000269|PubMed:9560228}.
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.
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. Phosphorylation of Thr-233 by CDK5 reduces AP-
CC endodeoxyribonuclease activity resulting in accumulation of DNA damage
CC and contributing to neuronal death. {ECO:0000269|PubMed:10023679,
CC ECO:0000269|PubMed:11452037}.
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.
CC {ECO:0000269|PubMed:14633989, ECO:0000269|PubMed:20699270}.
CC -!- PTM: Cleaved at Lys-31 by granzyme A to create the mitochondrial form;
CC leading in reduction of binding to DNA, AP endodeoxynuclease activity,
CC redox activation of transcription factors and to enhanced cell death.
CC Cleaved by granzyme K; leading to intracellular ROS accumulation and
CC enhanced cell death after oxidative stress.
CC -!- PTM: Cys-65 and Cys-93 are nitrosylated in response to nitric oxide
CC (NO) and lead to the exposure of the nuclear export signal (NES).
CC {ECO:0000269|PubMed:17403694}.
CC -!- PTM: Ubiquitinated by MDM2; leading to translocation to the cytoplasm
CC and proteasomal degradation. {ECO:0000269|PubMed:19219073}.
CC -!- MISCELLANEOUS: Extract of mitochondria, but not of nuclei or cytosol,
CC cleaves recombinant APEX1 to generate a mitochondrial APEX1-sized
CC product (By similarity). The specific activity of the cleaved
CC mitochondrial endodeoxyribonuclease appeared to be about 3-fold higher
CC than that of the full-length form. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the DNA repair enzymes AP/ExoA family.
CC {ECO:0000305}.
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 CCDS; CCDS9550.1; -.
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 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=2-318.
DR PDB; 1HD7; X-ray; 1.95 A; A=2-318.
DR PDB; 2ISI; X-ray; 2.76 A; A/B/C=2-318.
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 PDB; 4QH9; X-ray; 2.18 A; A=38-318.
DR PDB; 4QHD; X-ray; 1.65 A; A=38-318.
DR PDB; 4QHE; X-ray; 1.40 A; A=38-318.
DR PDB; 5CFG; X-ray; 1.80 A; A=44-318.
DR PDB; 5DFF; X-ray; 1.57 A; A/B=43-318.
DR PDB; 5DFH; X-ray; 1.95 A; A/B=43-318.
DR PDB; 5DFI; X-ray; 1.63 A; A/B=43-318.
DR PDB; 5DFJ; X-ray; 1.85 A; A/B=43-318.
DR PDB; 5DG0; X-ray; 1.80 A; A/B=43-318.
DR PDB; 5WN0; X-ray; 2.60 A; A/B=43-318.
DR PDB; 5WN1; X-ray; 2.30 A; A/B=43-318.
DR PDB; 5WN2; X-ray; 2.29 A; A/B=43-318.
DR PDB; 5WN3; X-ray; 2.00 A; A/B=43-318.
DR PDB; 5WN4; X-ray; 2.10 A; A/B=43-318.
DR PDB; 5WN5; X-ray; 2.20 A; A/B=43-318.
DR PDB; 6BOQ; X-ray; 1.96 A; A/B=1-318.
DR PDB; 6BOR; X-ray; 1.84 A; A/B=1-318.
DR PDB; 6BOS; X-ray; 2.30 A; A/B=1-318.
DR PDB; 6BOT; X-ray; 2.30 A; A/B=1-318.
DR PDB; 6BOU; X-ray; 2.54 A; A/B=1-318.
DR PDB; 6BOV; X-ray; 1.98 A; A/B=1-318.
DR PDB; 6BOW; X-ray; 1.59 A; A/B=1-318.
DR PDB; 6MK3; X-ray; 1.48 A; A=40-318.
DR PDB; 6MKK; X-ray; 1.44 A; A=40-318.
DR PDB; 6MKM; X-ray; 1.67 A; A=40-318.
DR PDB; 6MKO; X-ray; 2.09 A; A=40-318.
DR PDB; 6P93; X-ray; 2.10 A; A/B=43-318.
DR PDB; 6P94; X-ray; 2.09 A; A/B=43-318.
DR PDB; 6W0Q; X-ray; 1.89 A; A/B=43-318.
DR PDB; 6W2P; X-ray; 1.94 A; A/B=43-318.
DR PDB; 6W3L; X-ray; 2.59 A; A/B=43-318.
DR PDB; 6W3N; X-ray; 2.69 A; A/B=43-318.
DR PDB; 6W3Q; X-ray; 2.49 A; A/B=43-318.
DR PDB; 6W3U; X-ray; 2.40 A; A/B=43-318.
DR PDB; 6W43; X-ray; 1.99 A; A/B=43-318.
DR PDB; 6W4I; X-ray; 2.20 A; A/B=43-318.
DR PDB; 6W4T; X-ray; 2.77 A; A/B=43-318.
DR PDB; 7LPG; X-ray; 2.08 A; B/D=43-318.
DR PDB; 7LPH; X-ray; 1.99 A; B/D=43-318.
DR PDB; 7LPI; X-ray; 2.05 A; B/D=43-318.
DR PDB; 7LPJ; X-ray; 2.56 A; B/D=43-318.
DR PDB; 7MCR; X-ray; 1.90 A; A=44-318.
DR PDB; 7MEV; X-ray; 1.60 A; A=44-318.
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 PDBsum; 4QH9; -.
DR PDBsum; 4QHD; -.
DR PDBsum; 4QHE; -.
DR PDBsum; 5CFG; -.
DR PDBsum; 5DFF; -.
DR PDBsum; 5DFH; -.
DR PDBsum; 5DFI; -.
DR PDBsum; 5DFJ; -.
DR PDBsum; 5DG0; -.
DR PDBsum; 5WN0; -.
DR PDBsum; 5WN1; -.
DR PDBsum; 5WN2; -.
DR PDBsum; 5WN3; -.
DR PDBsum; 5WN4; -.
DR PDBsum; 5WN5; -.
DR PDBsum; 6BOQ; -.
DR PDBsum; 6BOR; -.
DR PDBsum; 6BOS; -.
DR PDBsum; 6BOT; -.
DR PDBsum; 6BOU; -.
DR PDBsum; 6BOV; -.
DR PDBsum; 6BOW; -.
DR PDBsum; 6MK3; -.
DR PDBsum; 6MKK; -.
DR PDBsum; 6MKM; -.
DR PDBsum; 6MKO; -.
DR PDBsum; 6P93; -.
DR PDBsum; 6P94; -.
DR PDBsum; 6W0Q; -.
DR PDBsum; 6W2P; -.
DR PDBsum; 6W3L; -.
DR PDBsum; 6W3N; -.
DR PDBsum; 6W3Q; -.
DR PDBsum; 6W3U; -.
DR PDBsum; 6W43; -.
DR PDBsum; 6W4I; -.
DR PDBsum; 6W4T; -.
DR PDBsum; 7LPG; -.
DR PDBsum; 7LPH; -.
DR PDBsum; 7LPI; -.
DR PDBsum; 7LPJ; -.
DR PDBsum; 7MCR; -.
DR PDBsum; 7MEV; -.
DR AlphaFoldDB; P27695; -.
DR BMRB; P27695; -.
DR SMR; P27695; -.
DR BioGRID; 106825; 1240.
DR CORUM; P27695; -.
DR DIP; DIP-6130N; -.
DR IntAct; P27695; 56.
DR MINT; P27695; -.
DR STRING; 9606.ENSP00000216714; -.
DR BindingDB; P27695; -.
DR ChEMBL; CHEMBL5619; -.
DR DrugBank; DB04967; Lucanthone.
DR DrugCentral; P27695; -.
DR GlyGen; P27695; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; P27695; -.
DR MetOSite; P27695; -.
DR PhosphoSitePlus; P27695; -.
DR SwissPalm; P27695; -.
DR BioMuta; APEX1; -.
DR DMDM; 113984; -.
DR CPTAC; CPTAC-23; -.
DR CPTAC; CPTAC-24; -.
DR EPD; P27695; -.
DR jPOST; P27695; -.
DR MassIVE; P27695; -.
DR PaxDb; P27695; -.
DR PeptideAtlas; P27695; -.
DR PRIDE; P27695; -.
DR ProteomicsDB; 54406; -.
DR TopDownProteomics; P27695; -.
DR Antibodypedia; 62; 937 antibodies from 46 providers.
DR CPTC; P27695; 1 antibody.
DR DNASU; 328; -.
DR Ensembl; ENST00000216714.8; ENSP00000216714.3; ENSG00000100823.12.
DR Ensembl; ENST00000398030.8; ENSP00000381111.4; ENSG00000100823.12.
DR Ensembl; ENST00000555414.5; ENSP00000451979.1; ENSG00000100823.12.
DR GeneID; 328; -.
DR KEGG; hsa:328; -.
DR MANE-Select; ENST00000216714.8; ENSP00000216714.3; NM_001641.4; NP_001632.2.
DR UCSC; uc058yte.1; human.
DR CTD; 328; -.
DR DisGeNET; 328; -.
DR GeneCards; APEX1; -.
DR HGNC; HGNC:587; APEX1.
DR HPA; ENSG00000100823; Low tissue specificity.
DR MIM; 107748; gene.
DR neXtProt; NX_P27695; -.
DR OpenTargets; ENSG00000100823; -.
DR PharmGKB; PA201059; -.
DR VEuPathDB; HostDB:ENSG00000100823; -.
DR eggNOG; KOG1294; Eukaryota.
DR GeneTree; ENSGT00530000063540; -.
DR HOGENOM; CLU_027539_1_3_1; -.
DR InParanoid; P27695; -.
DR OMA; WWSYRGR; -.
DR OrthoDB; 1105625at2759; -.
DR PhylomeDB; P27695; -.
DR TreeFam; TF315048; -.
DR BRENDA; 4.2.99.18; 2681.
DR PathwayCommons; P27695; -.
DR Reactome; R-HSA-110357; Displacement of DNA glycosylase by APEX1.
DR Reactome; R-HSA-110362; POLB-Dependent Long Patch Base Excision Repair.
DR Reactome; R-HSA-110373; Resolution of AP sites via the multiple-nucleotide patch replacement pathway.
DR Reactome; R-HSA-5651801; PCNA-Dependent Long Patch Base Excision Repair.
DR Reactome; R-HSA-73930; Abasic sugar-phosphate removal via the single-nucleotide replacement pathway.
DR Reactome; R-HSA-73933; Resolution of Abasic Sites (AP sites).
DR SignaLink; P27695; -.
DR SIGNOR; P27695; -.
DR BioGRID-ORCS; 328; 19 hits in 1082 CRISPR screens.
DR ChiTaRS; APEX1; human.
DR EvolutionaryTrace; P27695; -.
DR GeneWiki; APEX1; -.
DR GenomeRNAi; 328; -.
DR Pharos; P27695; Tchem.
DR PRO; PR:P27695; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P27695; protein.
DR Bgee; ENSG00000100823; Expressed in ganglionic eminence and 200 other tissues.
DR ExpressionAtlas; P27695; baseline and differential.
DR Genevisible; P27695; HS.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0000781; C:chromosome, telomeric region; IC:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
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:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; 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 regulator complex; IEA:Ensembl.
DR GO; GO:0008408; F:3'-5' exonuclease activity; IDA:UniProtKB.
DR GO; GO:0008296; F:3'-5'-exodeoxyribonuclease activity; IDA:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:UniProtKB.
DR GO; GO:0052720; F:class II DNA-(apurinic or apyrimidinic site) endonuclease activity; IDA:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0140431; F:DNA-(abasic site) binding; IMP:UniProtKB.
DR GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) endonuclease activity; IDA: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; IDA:BHF-UCL.
DR GO; GO:0003691; F:double-stranded telomeric DNA binding; IDA:BHF-UCL.
DR GO; GO:0004520; F:endodeoxyribonuclease activity; TAS:Reactome.
DR GO; GO:0004519; F:endonuclease activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IDA:UniProtKB.
DR GO; GO:0051059; F:NF-kappaB binding; IEA:Ensembl.
DR GO; GO:0016491; F:oxidoreductase activity; IDA:UniProtKB.
DR GO; GO:0090580; F:phosphodiesterase activity, acting on 3'-phosphoglycolate-terminated DNA strands; IDA:UniProtKB.
DR GO; GO:0004528; F:phosphodiesterase I activity; TAS:UniProtKB.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
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; IDA:CAFA.
DR GO; GO:0006287; P:base-excision repair, gap-filling; 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:0000737; P:DNA catabolic process, endonucleolytic; IDA:UniProtKB.
DR GO; GO:0080111; P:DNA demethylation; IDA:UniProtKB.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IDA:UniProtKB.
DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:ARUK-UCL.
DR GO; GO:0042981; P:regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; IMP:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0000723; P:telomere maintenance; IDA:BHF-UCL.
DR GO; GO:0097698; P:telomere maintenance via base-excision repair; IDA:BHF-UCL.
DR DisProt; DP00007; -.
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:12524539,
FT ECO:0000269|PubMed:1380454"
FT CHAIN 2..318
FT /note="DNA-(apurinic or apyrimidinic site) endonuclease"
FT /id="PRO_0000200010"
FT CHAIN 32..318
FT /note="DNA-(apurinic or apyrimidinic site) endonuclease,
FT mitochondrial"
FT /evidence="ECO:0000250"
FT /id="PRO_0000402572"
FT REGION 1..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..33
FT /note="Necessary for interaction with YBX1, binding to RNA,
FT NPM1-dependent association with rRNA, endoribonuclease
FT activity on abasic RNA and localization in the nucleoli"
FT /evidence="ECO:0000269|PubMed:18809583"
FT REGION 23..33
FT /note="Necessary for interaction with NPM1 and for
FT efficient rRNA binding"
FT REGION 289..318
FT /note="Mitochondrial targeting sequence (MTS)"
FT MOTIF 8..13
FT /note="Nuclear localization signal (NLS)"
FT MOTIF 64..80
FT /note="Nuclear export signal (NES)"
FT COMPBIAS 1..41
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 171
FT ACT_SITE 210
FT /note="Proton donor/acceptor"
FT BINDING 70
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT BINDING 96
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT BINDING 210
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT BINDING 212
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT BINDING 308
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT SITE 31..32
FT /note="Cleavage; by granzyme A"
FT SITE 212
FT /note="Transition state stabilizer"
FT SITE 283
FT /note="Important for catalytic activity"
FT SITE 309
FT /note="Interaction with DNA substrate"
FT MOD_RES 6
FT /note="N6-acetyllysine; by EP300"
FT /evidence="ECO:0000269|PubMed:14633989"
FT MOD_RES 7
FT /note="N6-acetyllysine; by EP300"
FT /evidence="ECO:0000269|PubMed:14633989"
FT MOD_RES 27
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:20699270"
FT MOD_RES 31
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:20699270"
FT MOD_RES 32
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:20699270"
FT MOD_RES 35
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:20699270"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 65
FT /note="S-nitrosocysteine; alternate"
FT /evidence="ECO:0000269|PubMed:17403694"
FT MOD_RES 93
FT /note="S-nitrosocysteine; alternate"
FT /evidence="ECO:0000269|PubMed:17403694"
FT MOD_RES 197
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 233
FT /note="Phosphothreonine; by CDK5"
FT /evidence="ECO:0000250|UniProtKB:P28352"
FT MOD_RES 310
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000269|PubMed:17403694"
FT DISULFID 65..93
FT /note="Alternate"
FT /evidence="ECO:0000305"
FT VARIANT 51
FT /note="Q -> H (in dbSNP:rs1048945)"
FT /evidence="ECO:0000269|Ref.11"
FT /id="VAR_013455"
FT VARIANT 64
FT /note="I -> V (in dbSNP:rs2307486)"
FT /evidence="ECO:0000269|Ref.11"
FT /id="VAR_014823"
FT VARIANT 148
FT /note="D -> E (in dbSNP:rs1130409)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.11"
FT /id="VAR_019790"
FT MUTAGEN 6
FT /note="K->R: Lack of acetylation, does not stimulate the
FT YBX1-mediated MDR1 promoter activity and alter nuclear
FT subcellular localization; when associated with R-7. Does
FT not inhibit interaction with HDAC1, HDAC2 and HDAC3.
FT Absence of increase in nCaRE binding activity."
FT /evidence="ECO:0000269|PubMed:14633989,
FT ECO:0000269|PubMed:15942031, ECO:0000269|PubMed:18809583,
FT ECO:0000269|PubMed:19934257"
FT MUTAGEN 7
FT /note="K->R: Lack of acetylation and does not stimulate the
FT YBX1-mediated MDR1 promoter activity and alter nuclear
FT subcellular localization; when associated with R-6."
FT /evidence="ECO:0000269|PubMed:14633989,
FT ECO:0000269|PubMed:15942031, ECO:0000269|PubMed:18809583,
FT ECO:0000269|PubMed:19934257"
FT MUTAGEN 12
FT /note="E->A: Reduces nuclear localization; when associated
FT with A-13."
FT /evidence="ECO:0000269|PubMed:15942031"
FT MUTAGEN 13
FT /note="D->A: Reduces nuclear localization; when associated
FT with A-12."
FT /evidence="ECO:0000269|PubMed:15942031"
FT MUTAGEN 24
FT /note="K->A: Enhances the interaction with TOMM20. Inhibits
FT rRNA binding, interaction with NPM1, nuclear localization
FT and modulates its endodeoxyribonuclease activity; when
FT associated with A-25; A-27; A-31 and A-32. Inhibits
FT ubiquitination; when associated with K-25 and K-27."
FT /evidence="ECO:0000269|PubMed:19219073,
FT ECO:0000269|PubMed:20231292, ECO:0000269|PubMed:20699270"
FT MUTAGEN 25
FT /note="K->A: Enhances the interaction with TOMM20. Inhibits
FT rRNA binding, interaction with NPM1, nuclear localization
FT and modulates its endodeoxyribonuclease activity; when
FT associated with A-24; A-27; A-31 and A-32. Inhibits
FT ubiquitination; when associated with K-24 and K-27."
FT /evidence="ECO:0000269|PubMed:19219073,
FT ECO:0000269|PubMed:20231292, ECO:0000269|PubMed:20699270"
FT MUTAGEN 27
FT /note="K->A: Enhances the interaction with TOMM20. Inhibits
FT rRNA binding, interaction with NPM1, nuclear localization
FT and modulates its endodeoyribonuclease activity; when
FT associated with A-24; A-25; A-31 and A-32. Inhibits
FT ubiquitination; when associated with K-24 and K-25."
FT /evidence="ECO:0000269|PubMed:19219073,
FT ECO:0000269|PubMed:20231292, ECO:0000269|PubMed:20699270"
FT MUTAGEN 31
FT /note="K->A: Enhances the interaction with TOMM20. Does not
FT inhibit redox and AP endodeoyribonuclease activities.
FT Inhibits rRNA binding, interaction with NPM1, nuclear
FT localization and modulates its endodeoxyribonuclease
FT activity; when associated with A-24; A-25; A-27 and A-32.
FT Reduces protection from granzyme A-mediated cell death;
FT when associated with A-65 and A-210."
FT /evidence="ECO:0000269|PubMed:12524539,
FT ECO:0000269|PubMed:20231292, ECO:0000269|PubMed:20699270"
FT MUTAGEN 32
FT /note="K->A: Inhibits rRNA binding, interaction with NPM1,
FT nuclear localization and modulates its
FT endodeoxyribonuclease activity; when associated with A-24;
FT A-25; A-27 and A-31."
FT /evidence="ECO:0000269|PubMed:20699270"
FT MUTAGEN 65
FT /note="C->A: Abolishes the redox activity. Does not abolish
FT the AP endodeoxyribonuclease and phosphodiesterase
FT activities. Reduces protection from granzyme A-mediated
FT cell death; when associated with A-31 and A-210."
FT /evidence="ECO:0000269|PubMed:12524539,
FT ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:8355688"
FT MUTAGEN 65
FT /note="C->S: Does not abolish NO-induced nitrosylation.
FT Enhances NO-induced nuclear export."
FT /evidence="ECO:0000269|PubMed:12524539,
FT ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:8355688"
FT MUTAGEN 68
FT /note="N->A: Nearly abolishes AP endodeoxyribonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:21762700"
FT MUTAGEN 70
FT /note="D->A: Strongly reduces AP endodeoxyribonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:21762700"
FT MUTAGEN 93
FT /note="C->A: Abolishes partially the redox activity."
FT /evidence="ECO:0000269|PubMed:18579163,
FT ECO:0000269|PubMed:8355688"
FT MUTAGEN 93
FT /note="C->S: Does not abolish NO-induced nitrosylation.
FT Abolishes NO-induced nitrosylation and translocation from
FT the nucleus to the cytoplasm; when associated with S-310."
FT /evidence="ECO:0000269|PubMed:18579163,
FT ECO:0000269|PubMed:8355688"
FT MUTAGEN 96
FT /note="E->A: Lacks MYC CRD RNA cleavage activity."
FT /evidence="ECO:0000269|PubMed:19401441"
FT MUTAGEN 99
FT /note="C->A: Does not abolish the redox activity."
FT /evidence="ECO:0000269|PubMed:18579163,
FT ECO:0000269|PubMed:8355688"
FT MUTAGEN 138
FT /note="C->A: Does not abolish the redox activity."
FT /evidence="ECO:0000269|PubMed:18579163,
FT ECO:0000269|PubMed:8355688"
FT MUTAGEN 171
FT /note="Y->A,F,H: Abolishes the AP endodeoxyribonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:15380100,
FT ECO:0000269|PubMed:21762700"
FT MUTAGEN 208
FT /note="C->A: Does not abolish the redox activity."
FT /evidence="ECO:0000269|PubMed:18579163,
FT ECO:0000269|PubMed:8355688"
FT MUTAGEN 210
FT /note="D->A,N: Abolishes the AP endodeoxyribonuclease
FT activity. Reduces protection from granzyme A-mediated cell
FT death; when associated with A-31 and A-65."
FT /evidence="ECO:0000269|PubMed:12524539"
FT MUTAGEN 212
FT /note="N->A: Abolishes AP endodeoxyribonuclease activity."
FT /evidence="ECO:0000269|PubMed:8932375"
FT MUTAGEN 212
FT /note="N->Q,D: Decreases AP endodeoxyribonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:8932375"
FT MUTAGEN 266
FT /note="F->A: Strongly reduces AP endodeoxyribonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:21762700"
FT MUTAGEN 283
FT /note="D->A: Strongly reduces AP endodeoxyribonuclease
FT activity, but does not affect RNA cleavage activity. Nearly
FT abolishes AP endodeoxyribonuclease activity; when
FT associated with A-308."
FT /evidence="ECO:0000269|PubMed:21762700,
FT ECO:0000269|PubMed:9804799"
FT MUTAGEN 296
FT /note="C->A: Does not abolish the redox activity."
FT /evidence="ECO:0000269|PubMed:18579163,
FT ECO:0000269|PubMed:8355688"
FT MUTAGEN 299
FT /note="K->A: Reduces the interaction with TOMM20. Abolishes
FT localization in the mitochondria; when associated with A-
FT 301."
FT /evidence="ECO:0000269|PubMed:20231292"
FT MUTAGEN 301
FT /note="R->A: Reduces the interaction with TOMM20. Abolishes
FT localization in the mitochondria; when associated with A-
FT 299."
FT /evidence="ECO:0000269|PubMed:20231292"
FT MUTAGEN 303
FT /note="K->A: Reduces the interaction with TOMM20."
FT /evidence="ECO:0000269|PubMed:20231292"
FT MUTAGEN 308
FT /note="D->A: Reduces AP endodeoxyribonuclease activity.
FT Nearly abolishes AP endodeoxyribonuclease activity; when
FT associated with A-283."
FT /evidence="ECO:0000269|PubMed:21762700,
FT ECO:0000269|PubMed:9804799"
FT MUTAGEN 309
FT /note="H->N,S: Abolishes AP endodeoxyribonuclease activity.
FT Lacks MYC CRD RNA cleavage activity."
FT /evidence="ECO:0000269|PubMed:19401441,
FT ECO:0000269|PubMed:21762700, ECO:0000269|PubMed:9804799"
FT MUTAGEN 310
FT /note="C->A: Does not abolish the redox activity."
FT /evidence="ECO:0000269|PubMed:18579163,
FT ECO:0000269|PubMed:8355688"
FT MUTAGEN 310
FT /note="C->S: Does not abolish NO-induced nitrosylation.
FT Abolishes NO-induced nitrosylation and translocation from
FT the nucleus to the cytoplasm; when associated with S-93."
FT /evidence="ECO:0000269|PubMed:18579163,
FT ECO:0000269|PubMed:8355688"
FT CONFLICT 57
FT /note="G -> A (in Ref. 2; AAA58371)"
FT /evidence="ECO:0000305"
FT CONFLICT 306
FT /note="G -> A (in Ref. 2; AAA58371)"
FT /evidence="ECO:0000305"
FT STRAND 62..68
FT /evidence="ECO:0007829|PDB:4QHE"
FT HELIX 72..77
FT /evidence="ECO:0007829|PDB:4QHE"
FT HELIX 80..87
FT /evidence="ECO:0007829|PDB:4QHE"
FT STRAND 90..95
FT /evidence="ECO:0007829|PDB:4QHE"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:5DFF"
FT HELIX 106..110
FT /evidence="ECO:0007829|PDB:4QHE"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:4QHE"
FT STRAND 116..120
FT /evidence="ECO:0007829|PDB:4QHE"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:6BOR"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:4QHE"
FT STRAND 131..137
FT /evidence="ECO:0007829|PDB:4QHE"
FT STRAND 140..145
FT /evidence="ECO:0007829|PDB:4QHE"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:4QHE"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:4QHE"
FT STRAND 157..161
FT /evidence="ECO:0007829|PDB:4QHE"
FT STRAND 166..171
FT /evidence="ECO:0007829|PDB:4QHE"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:4QHE"
FT HELIX 182..200
FT /evidence="ECO:0007829|PDB:4QHE"
FT STRAND 205..210
FT /evidence="ECO:0007829|PDB:4QHE"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:4QHE"
FT TURN 224..228
FT /evidence="ECO:0007829|PDB:4QHE"
FT TURN 230..232
FT /evidence="ECO:0007829|PDB:7LPI"
FT HELIX 234..246
FT /evidence="ECO:0007829|PDB:4QHE"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:6W3N"
FT HELIX 252..256
FT /evidence="ECO:0007829|PDB:4QHE"
FT STRAND 257..259
FT /evidence="ECO:0007829|PDB:1DE9"
FT HELIX 270..272
FT /evidence="ECO:0007829|PDB:6BOW"
FT HELIX 273..276
FT /evidence="ECO:0007829|PDB:4QHE"
FT STRAND 283..287
FT /evidence="ECO:0007829|PDB:4QHE"
FT HELIX 289..294
FT /evidence="ECO:0007829|PDB:4QHE"
FT STRAND 295..300
FT /evidence="ECO:0007829|PDB:4QHE"
FT STRAND 306..309
FT /evidence="ECO:0007829|PDB:4QHE"
FT STRAND 312..316
FT /evidence="ECO:0007829|PDB:4QHE"
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
