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 27-MAR-2024, entry version 261. DE RecName: Full=DNA repair nuclease/redox regulator APEX1; DE EC=3.1.11.2 {ECO:0000269|PubMed:11286553, ECO:0000269|PubMed:15380100, ECO:0000269|PubMed:19123919, ECO:0000269|PubMed:21762700}; DE EC=3.1.21.- {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=DNA-(apurinic or apyrimidinic site) endonuclease; DE AltName: Full=REF-1; DE AltName: Full=Redox factor-1; DE Contains: DE RecName: Full=DNA repair nuclease/redox regulator APEX1, mitochondrial; GN Name=APEX1; Synonyms=APE, 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 INTERACTION WITH POLB. RX PubMed=26760506; DOI=10.18632/oncotarget.6849; RA Zhou T., Pan F., Cao Y., Han Y., Zhao J., Sun H., Zhou X., Wu X., He L., RA Hu Z., Chen H., Shen B., Guo Z.; RT "R152C DNA Pol beta mutation impairs base excision repair and induces RT cellular transformation."; RL Oncotarget 7:6902-6915(2016). RN [42] 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 [43] 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 [44] 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 [45] 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 [46] 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 [47] 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 [48] 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 [49] 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 [50] 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 [51] 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 [52] 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 [53] 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 [54] {ECO:0007744|PDB:1BIX} 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 [55] {ECO:0007744|PDB:1DE8, ECO:0007744|PDB:1DE9, ECO:0007744|PDB:1DEW} 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 [56] {ECO:0007744|PDB:1E9N, ECO:0007744|PDB:1HD7} 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 an apurinic/apyrimidinic (AP) endodeoxyribonuclease in the CC DNA base excision repair (BER) pathway of DNA lesions induced by CC oxidative and alkylating agents. Initiates repair of AP sites in DNA by CC catalyzing hydrolytic incision of the phosphodiester backbone CC immediately adjacent to the damage, generating a single-strand break CC with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Also incises at AP CC sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions CC of R-loop structures, and single-stranded RNA molecules. Has 3'-5' CC exoribonuclease activity on mismatched deoxyribonucleotides at the 3' CC termini of nicked or gapped DNA molecules during short-patch BER. CC Possesses DNA 3' phosphodiesterase activity capable of removing lesions CC (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. CC May also play a role in the epigenetic regulation of gene expression by CC participating in DNA demethylation. Acts as a loading factor for POLB CC onto non-incised AP sites in DNA and stimulates the 5'-terminal CC deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role CC in protection from granzyme-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 reversible CC nuclear redox activity to regulate DNA binding affinity and CC transcriptional activity of transcriptional factors by controlling the CC redox status of their DNA-binding domain, such as the FOS/JUN AP-1 CC complex after exposure to IR. Involved in calcium-dependent down- CC regulation of parathyroid hormone (PTH) expression by binding to CC negative calcium response elements (nCaREs). Together with HNRNPL or CC the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of CC transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter CC activity, when acetylated at Lys-6 and Lys-7, leading to drug CC resistance. Acts also as an endoribonuclease involved in the control of CC single-stranded RNA metabolism. Plays a role in regulating MYC mRNA CC turnover by preferentially cleaving in between UA and CA dinucleotides CC of the MYC coding region determinant (CRD). In association with NMD1, CC plays a role in the rRNA quality control process during cell cycle CC progression. Associates, together with YBX1, on the MDR1 promoter. CC Together with NPM1, associates with rRNA. Binds DNA and RNA. CC {ECO:0000269|PubMed: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 -!- 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 {ECO:0000269|PubMed:19188445}. 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, PRDX6, PRPF19, RPLP0, TOMM20 and WDR77. Interacts with POLB CC (PubMed:9207062, PubMed:26760506). Binds to CDK5. CC {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:26760506, CC ECO:0000269|PubMed:8621488, ECO:0000269|PubMed:9108029, CC ECO:0000269|PubMed:9207062, 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 {ECO:0000255|PROSITE-ProRule:PRU00764}. CC Nucleus, nucleolus. Nucleus speckle. Endoplasmic reticulum. Cytoplasm. CC Note=Detected in the cytoplasm of B-cells stimulated to switch (By CC similarity). Colocalized with SIRT1 in the nucleus. Colocalized with CC YBX1 in nuclear speckles after genotoxic stress. Together with OGG1 is CC recruited to nuclear speckles in UVA-irradiated cells. Colocalized with CC nucleolin and NPM1 in the nucleolus. Its nucleolar localization is cell CC cycle dependent and requires active rRNA transcription. Colocalized CC with calreticulin in the endoplasmic reticulum. Translocation from the CC nucleus to the cytoplasm is stimulated in presence of nitric oxide (NO) CC and function in a CRM1-dependent manner, possibly as a consequence of CC demasking a nuclear export signal (amino acid position 64-80). S- CC nitrosylation at Cys-93 and Cys-310 regulates its nuclear-cytosolic CC shuttling. Ubiquitinated form is localized predominantly in the CC cytoplasm. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: [DNA repair nuclease/redox regulator APEX1, CC mitochondrial]: Mitochondrion. Note=The cleaved APEX2 is only detected CC in mitochondria (By similarity). Translocation from the cytoplasm to CC the mitochondria is mediated by ROS signaling and cleavage mediated by CC granzyme A. Tom20-dependent translocated mitochondrial APEX1 level is CC significantly increased after genotoxic stress. {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 functions 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 to 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 {ECO:0000269|PubMed:12524539}. 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 appears to be about 3-fold higher CC than that of the full-length form. {ECO:0000250|UniProtKB:P23196}. 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 PDB; 7SUV; X-ray; 1.99 A; A/B=43-318. DR PDB; 7SVB; X-ray; 2.24 A; A/B=43-318. DR PDB; 7TC2; X-ray; 1.43 A; A/B/C/D=39-318. DR PDB; 7TC3; X-ray; 1.25 A; A=39-318. DR PDB; 7TR7; X-ray; 2.00 A; A/B=43-318. DR PDB; 7U50; EM; 3.40 A; K=1-318. 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 PDBsum; 7SUV; -. DR PDBsum; 7SVB; -. DR PDBsum; 7TC2; -. DR PDBsum; 7TC3; -. DR PDBsum; 7TR7; -. DR PDBsum; 7U50; -. DR AlphaFoldDB; P27695; -. DR BMRB; P27695; -. DR EMDB; EMD-26336; -. DR SMR; P27695; -. DR BioGRID; 106825; 1259. 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 MoonProt; P27695; -. DR GlyCosmos; P27695; 1 site, 2 glycans. 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; 9606-ENSP00000216714; -. DR PeptideAtlas; P27695; -. DR ProteomicsDB; 54406; -. DR Pumba; P27695; -. DR TopDownProteomics; P27695; -. DR Antibodypedia; 62; 1100 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 Ensembl; ENST00000708787.1; ENSP00000517339.1; ENSG00000291796.1. DR Ensembl; ENST00000708794.1; ENSP00000517342.1; ENSG00000291796.1. DR Ensembl; ENST00000708795.1; ENSP00000517343.1; ENSG00000291796.1. 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 AGR; HGNC:587; -. 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; 161558at2759; -. 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; 22 hits in 1167 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 202 other cell types or tissues. DR ExpressionAtlas; P27695; baseline and differential. 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:0008408; F:3'-5' exonuclease activity; IDA:UniProtKB. DR GO; GO:0008296; F:3'-5'-DNA exonuclease 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:0004520; F:DNA endonuclease activity; TAS:Reactome. 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' DNA exonuclease 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:0004519; F:endonuclease activity; IDA:MGI. DR GO; GO:0046872; F:metal ion binding; IDA:UniProtKB. 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: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: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:0006308; P:DNA catabolic process; 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: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:0000723; P:telomere maintenance; IDA:BHF-UCL. DR GO; GO:0097698; P:telomere maintenance via base-excision repair; IDA:BHF-UCL. DR CDD; cd09087; Ape1-like_AP-endo; 1. DR DisProt; DP00007; -. DR Gene3D; 3.60.10.10; Endonuclease/exonuclease/phosphatase; 1. DR InterPro; IPR004808; AP_endonuc_1. DR InterPro; IPR020847; AP_endonuclease_F1_BS. DR InterPro; IPR020848; AP_endonuclease_F1_CS. DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf. DR InterPro; IPR005135; Endo/exonuclease/phosphatase. DR NCBIfam; TIGR00195; exoDNase_III; 1. DR NCBIfam; TIGR00633; xth; 1. DR PANTHER; PTHR22748; AP ENDONUCLEASE; 1. DR PANTHER; PTHR22748:SF6; DNA-(APURINIC OR APYRIMIDINIC SITE) ENDONUCLEASE; 1. DR Pfam; PF03372; Exo_endo_phos; 1. DR SUPFAM; SSF56219; DNase I-like; 1. DR PROSITE; PS00726; AP_NUCLEASE_F1_1; 1. DR PROSITE; PS00727; AP_NUCLEASE_F1_2; 1. DR PROSITE; PS00728; AP_NUCLEASE_F1_3; 1. DR PROSITE; PS51435; AP_NUCLEASE_F1_4; 1. DR Genevisible; P27695; HS. 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 repair nuclease/redox regulator APEX1" FT /id="PRO_0000200010" FT CHAIN 32..318 FT /note="DNA repair nuclease/redox regulator APEX1, 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 /evidence="ECO:0000269|PubMed:15380100" FT ACT_SITE 210 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000269|PubMed:9351835, FT ECO:0007744|PDB:1BIX" FT ACT_SITE 309 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00764" FT BINDING 68 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00764" FT BINDING 96 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00764" FT BINDING 210 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00764" FT BINDING 212 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00764" FT BINDING 308 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00764" FT BINDING 309 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00764" FT SITE 31..32 FT /note="Cleavage; by granzyme A" FT SITE 212 FT /note="Transition state stabilizer" FT /evidence="ECO:0000269|PubMed:8932375" FT SITE 283 FT /note="Important for catalytic activity" FT /evidence="ECO:0000269|PubMed:21762700, FT ECO:0000269|PubMed:9804799" 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 MYCCRDRNA 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 FT A-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 FT A-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 MYCCRDRNA 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:7TC3" FT HELIX 72..77 FT /evidence="ECO:0007829|PDB:7TC3" FT HELIX 80..87 FT /evidence="ECO:0007829|PDB:7TC3" FT STRAND 90..95 FT /evidence="ECO:0007829|PDB:7TC3" FT HELIX 101..103 FT /evidence="ECO:0007829|PDB:5DFF" FT HELIX 106..110 FT /evidence="ECO:0007829|PDB:7TC3" FT HELIX 112..114 FT /evidence="ECO:0007829|PDB:4QHE" FT STRAND 116..120 FT /evidence="ECO:0007829|PDB:7TC3" FT STRAND 122..124 FT /evidence="ECO:0007829|PDB:7MEV" FT STRAND 127..129 FT /evidence="ECO:0007829|PDB:4QHE" FT STRAND 131..137 FT /evidence="ECO:0007829|PDB:7TC3" FT STRAND 140..145 FT /evidence="ECO:0007829|PDB:7TC3" FT HELIX 149..151 FT /evidence="ECO:0007829|PDB:7TC3" FT STRAND 152..155 FT /evidence="ECO:0007829|PDB:7TC3" FT STRAND 157..161 FT /evidence="ECO:0007829|PDB:7TC3" FT STRAND 166..171 FT /evidence="ECO:0007829|PDB:7TC3" FT HELIX 177..179 FT /evidence="ECO:0007829|PDB:7TC3" FT HELIX 182..200 FT /evidence="ECO:0007829|PDB:7TC3" FT STRAND 205..210 FT /evidence="ECO:0007829|PDB:7TC3" FT HELIX 217..219 FT /evidence="ECO:0007829|PDB:7TC3" FT TURN 224..228 FT /evidence="ECO:0007829|PDB:7TC3" FT TURN 230..232 FT /evidence="ECO:0007829|PDB:7LPI" FT HELIX 234..246 FT /evidence="ECO:0007829|PDB:7TC3" FT STRAND 249..251 FT /evidence="ECO:0007829|PDB:7MCR" FT HELIX 252..256 FT /evidence="ECO:0007829|PDB:7TC3" FT STRAND 257..259 FT /evidence="ECO:0007829|PDB:1DE9" FT STRAND 265..267 FT /evidence="ECO:0007829|PDB:7U50" FT HELIX 270..272 FT /evidence="ECO:0007829|PDB:6BOW" FT HELIX 273..276 FT /evidence="ECO:0007829|PDB:7TC3" FT STRAND 283..287 FT /evidence="ECO:0007829|PDB:7TC3" FT HELIX 289..294 FT /evidence="ECO:0007829|PDB:7TC3" FT STRAND 295..300 FT /evidence="ECO:0007829|PDB:7TC3" FT STRAND 306..309 FT /evidence="ECO:0007829|PDB:7TC3" FT STRAND 312..316 FT /evidence="ECO:0007829|PDB:7TC3" 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 //