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P27695

- APEX1_HUMAN

UniProt

P27695 - APEX1_HUMAN

Protein

DNA-(apurinic or apyrimidinic site) lyase

Gene

APEX1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 185 (01 Oct 2014)
      Sequence version 2 (23 Jan 2007)
      Previous versions | rss
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    Functioni

    Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 in DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA.25 Publications

    Catalytic activityi

    The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate.5 PublicationsPROSITE-ProRule annotation

    Cofactori

    Magnesium. Can also utilize manganese. Probably binds two magnesium or manganese ions per subunit.4 Publications

    Enzyme regulationi

    NPM1 stimulates endodeoxyribonuclease activity on double-stranded DNA with AP sites, but inhibits endoribonuclease activity on single-stranded RNA containing AP sites.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei31 – 322Cleavage; by granzyme A
    Metal bindingi70 – 701Magnesium 1
    Metal bindingi96 – 961Magnesium 1
    Active sitei171 – 1711
    Active sitei210 – 2101Proton donor/acceptor
    Metal bindingi210 – 2101Magnesium 2
    Metal bindingi212 – 2121Magnesium 2
    Sitei212 – 2121Transition state stabilizer
    Sitei283 – 2831Important for catalytic activity
    Metal bindingi308 – 3081Magnesium 1
    Sitei309 – 3091Interaction with DNA substrate

    GO - Molecular functioni

    1. 3'-5' exonuclease activity Source: UniProtKB
    2. chromatin DNA binding Source: UniProtKB
    3. damaged DNA binding Source: UniProtKB
    4. DNA-(apurinic or apyrimidinic site) lyase activity Source: UniProtKB
    5. DNA binding Source: UniProtKB
    6. double-stranded DNA 3'-5' exodeoxyribonuclease activity Source: RefGenome
    7. endodeoxyribonuclease activity Source: ProtInc
    8. endonuclease activity Source: MGI
    9. metal ion binding Source: UniProtKB
    10. oxidoreductase activity Source: UniProtKB
    11. phosphodiesterase I activity Source: UniProtKB
    12. phosphoric diester hydrolase activity Source: MGI
    13. poly(A) RNA binding Source: UniProtKB
    14. protein binding Source: UniProtKB
    15. RNA-DNA hybrid ribonuclease activity Source: UniProtKB
    16. site-specific endodeoxyribonuclease activity, specific for altered base Source: UniProtKB
    17. transcription coactivator activity Source: UniProtKB
    18. transcription corepressor activity Source: ProtInc
    19. uracil DNA N-glycosylase activity Source: ProtInc

    GO - Biological processi

    1. aging Source: Ensembl
    2. base-excision repair Source: RefGenome
    3. cell redox homeostasis Source: Ensembl
    4. cellular response to cAMP Source: Ensembl
    5. cellular response to hydrogen peroxide Source: Ensembl
    6. cellular response to peptide hormone stimulus Source: Ensembl
    7. DNA catabolic process, endonucleolytic Source: GOC
    8. DNA catabolic process, exonucleolytic Source: GOC
    9. DNA demethylation Source: UniProtKB
    10. DNA recombination Source: UniProtKB-KW
    11. DNA repair Source: UniProtKB
    12. negative regulation of smooth muscle cell migration Source: Ensembl
    13. nucleic acid phosphodiester bond hydrolysis Source: GOC
    14. oxidation-reduction process Source: GOC
    15. positive regulation of DNA repair Source: UniProtKB
    16. positive regulation of G1/S transition of mitotic cell cycle Source: Ensembl
    17. regulation of mRNA stability Source: UniProtKB
    18. regulation of transcription, DNA-templated Source: UniProtKB-KW
    19. response to drug Source: Ensembl
    20. RNA phosphodiester bond hydrolysis, endonucleolytic Source: GOC
    21. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator, Endonuclease, Exonuclease, Hydrolase, Lyase, Nuclease, Repressor

    Keywords - Biological processi

    DNA damage, DNA recombination, DNA repair, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Magnesium, Metal-binding, RNA-binding

    Enzyme and pathway databases

    BRENDAi4.2.99.18. 2681.
    ReactomeiREACT_1064. Displacement of DNA glycosylase by APE1.
    REACT_1128. Resolution of AP sites via the multiple-nucleotide patch replacement pathway.
    REACT_1357. Base-free sugar-phosphate removal via the single-nucleotide replacement pathway.
    REACT_2192. Removal of DNA patch containing abasic residue.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    DNA-(apurinic or apyrimidinic site) lyase (EC:3.1.-.-, EC:4.2.99.18)
    Alternative name(s):
    APEX nuclease
    Short name:
    APEN
    Apurinic-apyrimidinic endonuclease 1
    Short name:
    AP endonuclease 1
    Short name:
    APE-1
    REF-1
    Redox factor-1
    Cleaved into the following chain:
    Gene namesi
    Name:APEX1
    Synonyms:APE, APE1, APEX, APX, HAP1, REF1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:587. APEX1.

    Subcellular locationi

    Nucleus. Nucleusnucleolus. Nucleus speckle. Endoplasmic reticulum. Cytoplasm
    Note: Detected in the cytoplasm of B-cells stimulated to switch By similarity. Colocalized with SIRT1 in the nucleus. Colocalized with YBX1 in nuclear speckles after genotoxic stress. Together with OGG1 is recruited to nuclear speckles in UVA-irradiated cells. Colocalized with nucleolin and NPM1 in the nucleolus. Its nucleolar localization is cell cycle dependent and requires active rRNA transcription. Colocalized with calreticulin in the endoplasmic reticulum. Translocation from the nucleus to the cytoplasm is stimulated in presence of nitric oxide (NO) and function in a CRM1-dependent manner, possibly as a consequence of demasking a nuclear export signal (amino acid position 64-80). S-nitrosylation at Cys-93 and Cys-310 regulates its nuclear-cytosolic shuttling. Ubiquitinated form is localized predominantly in the cytoplasm.By similarity
    Chain DNA-(apurinic or apyrimidinic site) lyase, mitochondrial : Mitochondrion
    Note: The cleaved APEX2 is only detected in mitochondria By similarity. Translocation from the cytoplasm to the mitochondria is mediated by ROS signaling and cleavage mediated by granzyme A. Tom20-dependent translocated mitochondrial APEX1 level is significantly increased after genotoxic stress.By similarity

    GO - Cellular componenti

    1. centrosome Source: HPA
    2. cytoplasm Source: UniProtKB
    3. endoplasmic reticulum Source: UniProtKB
    4. mitochondrion Source: UniProtKB
    5. nuclear speck Source: UniProtKB
    6. nucleolus Source: UniProtKB
    7. nucleoplasm Source: UniProtKB
    8. nucleus Source: UniProtKB
    9. perinuclear region of cytoplasm Source: UniProtKB
    10. ribosome Source: UniProtKB
    11. transcription factor complex Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Endoplasmic reticulum, Mitochondrion, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi6 – 61K → R: Lack of acetylation, does not stimulate the YBX1-mediated MDR1 promoter activity and alter nuclear subcellular localization; when associated with R-7. Does not inhibit interaction with HDAC1, HDAC2 and HDAC3. Absence of increase in nCaRE binding activity. 4 Publications
    Mutagenesisi7 – 71K → R: Lack of acetylation and does not stimulate the YBX1-mediated MDR1 promoter activity and alter nuclear subcellular localization; when associated with R-6. 4 Publications
    Mutagenesisi12 – 121E → A: Reduces nuclear localization; when associated with A-13. 1 Publication
    Mutagenesisi13 – 131D → A: Reduces nuclear localization; when associated with A-12. 1 Publication
    Mutagenesisi24 – 241K → A: Enhances the interaction with TOMM20. Inhibits rRNA binding, interaction with NPM1, nuclear localization and modulates its endodeoxyribonuclease activity; when associated with A-25; A-27; A-31 and A-32. Inhibits ubiquitination; when associated with K-25 and K-27. 3 Publications
    Mutagenesisi25 – 251K → A: Enhances the interaction with TOMM20. Inhibits rRNA binding, interaction with NPM1, nuclear localization and modulates its endodeoxyribonuclease activity; when associated with A-24; A-27; A-31 and A-32. Inhibits ubiquitination; when associated with K-24 and K-27. 3 Publications
    Mutagenesisi27 – 271K → A: Enhances the interaction with TOMM20. Inhibits rRNA binding, interaction with NPM1, nuclear localization and modulates its endodeoyribonuclease activity; when associated with A-24; A-25; A-31 and A-32. Inhibits ubiquitination; when associated with K-24 and K-25. 3 Publications
    Mutagenesisi31 – 311K → A: Enhances the interaction with TOMM20. Does not inhibit redox and AP endodeoyribonuclease activities. Inhibits rRNA binding, interaction with NPM1, nuclear localization and modulates its endodeoxyribonuclease activity; when associated with A-24; A-25; A-27 and A-32. Reduces protection from granzyme A-mediated cell death; when associated with A-65 and A-210. 3 Publications
    Mutagenesisi32 – 321K → A: Inhibits rRNA binding, interaction with NPM1, nuclear localization and modulates its endodeoxyribonuclease activity; when associated with A-24; A-25; A-27 and A-31. 1 Publication
    Mutagenesisi65 – 651C → A: Abolishes the redox activity. Does not abolish the AP endodeoxyribonuclease and phosphodiesterase activities. Reduces protection from granzyme A-mediated cell death; when associated with A-31 and A-210. 3 Publications
    Mutagenesisi65 – 651C → S: Does not abolish NO-induced nitrosylation. Enhances NO-induced nuclear export. 3 Publications
    Mutagenesisi68 – 681N → A: Nearly abolishes AP endodeoxyribonuclease activity. 1 Publication
    Mutagenesisi70 – 701D → A: Strongly reduces AP endodeoxyribonuclease activity. 1 Publication
    Mutagenesisi93 – 931C → A: Abolishes partially the redox activity. 2 Publications
    Mutagenesisi93 – 931C → S: Does not abolish NO-induced nitrosylation. Abolishes NO-induced nitrosylation and translocation from the nucleus to the cytoplasm; when associated with S-310. 2 Publications
    Mutagenesisi96 – 961E → A: Lacks MYC CRD RNA cleavage activity. 1 Publication
    Mutagenesisi99 – 991C → A: Does not abolish the redox activity. 2 Publications
    Mutagenesisi138 – 1381C → A: Does not abolish the redox activity. 2 Publications
    Mutagenesisi171 – 1711Y → A, F or H: Abolishes the AP endodeoxyribonuclease activity. 2 Publications
    Mutagenesisi208 – 2081C → A: Does not abolish the redox activity. 2 Publications
    Mutagenesisi210 – 2101D → A or N: Abolishes the AP endodeoxyribonuclease activity. Reduces protection from granzyme A-mediated cell death; when associated with A-31 and A-65. 1 Publication
    Mutagenesisi212 – 2121N → A: Abolishes AP endodeoxyribonuclease activity. 1 Publication
    Mutagenesisi212 – 2121N → Q or D: Decreases AP endodeoxyribonuclease activity. 1 Publication
    Mutagenesisi266 – 2661F → A: Strongly reduces AP endodeoxyribonuclease activity. 1 Publication
    Mutagenesisi283 – 2831D → A: Strongly reduces AP endodeoxyribonuclease activity, but does not affect RNA cleavage activity. Nearly abolishes AP endodeoxyribonuclease activity; when associated with A-308. 2 Publications
    Mutagenesisi296 – 2961C → A: Does not abolish the redox activity. 2 Publications
    Mutagenesisi299 – 2991K → A: Reduces the interaction with TOMM20. Abolishes localization in the mitochondria; when associated with A-301. 1 Publication
    Mutagenesisi301 – 3011R → A: Reduces the interaction with TOMM20. Abolishes localization in the mitochondria; when associated with A-299. 1 Publication
    Mutagenesisi303 – 3031K → A: Reduces the interaction with TOMM20. 1 Publication
    Mutagenesisi308 – 3081D → A: Reduces AP endodeoxyribonuclease activity. Nearly abolishes AP endodeoxyribonuclease activity; when associated with A-283. 2 Publications
    Mutagenesisi309 – 3091H → N or S: Abolishes AP endodeoxyribonuclease activity. Lacks MYC CRD RNA cleavage activity. 3 Publications
    Mutagenesisi310 – 3101C → A: Does not abolish the redox activity. 2 Publications
    Mutagenesisi310 – 3101C → S: Does not abolish NO-induced nitrosylation. Abolishes NO-induced nitrosylation and translocation from the nucleus to the cytoplasm; when associated with S-93. 2 Publications

    Organism-specific databases

    PharmGKBiPA201059.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed2 Publications
    Chaini2 – 318317DNA-(apurinic or apyrimidinic site) lyasePRO_0000200010Add
    BLAST
    Chaini32 – 318287DNA-(apurinic or apyrimidinic site) lyase, mitochondrialBy similarityPRO_0000402572Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei6 – 61N6-acetyllysine; by EP3001 Publication
    Modified residuei7 – 71N6-acetyllysine; by EP3001 Publication
    Modified residuei27 – 271N6-acetyllysine1 Publication
    Modified residuei31 – 311N6-acetyllysine1 Publication
    Modified residuei32 – 321N6-acetyllysine1 Publication
    Modified residuei35 – 351N6-acetyllysine1 Publication
    Disulfide bondi65 ↔ 93AlternateCurated
    Modified residuei65 – 651S-nitrosocysteine; alternate1 Publication
    Modified residuei93 – 931S-nitrosocysteine; alternate1 Publication
    Modified residuei197 – 1971N6-acetyllysine1 Publication
    Modified residuei233 – 2331Phosphothreonine; by CDK5By similarity
    Modified residuei310 – 3101S-nitrosocysteine1 Publication

    Post-translational modificationi

    Phosphorylated. Phosphorylation by kinase PKC or casein kinase CK2 results in enhanced redox activity that stimulates binding of the FOS/JUN AP-1 complex to its cognate binding site. AP-endodeoxyribonuclease activity is not affected by CK2-mediated phosphorylation. Phosphorylation of Thr-233 by CDK5 reduces AP-endodeoxyribonuclease activity resulting in accumulation of DNA damage and contributing to neuronal death.2 Publications
    Acetylated on Lys-6 and Lys-7. Acetylation is increased by the transcriptional coactivator EP300 acetyltransferase, genotoxic agents like H2O2 and methyl methanesulfonate (MMS). Acetylation increases its binding affinity to the negative calcium response element (nCaRE) DNA promoter. The acetylated form induces a stronger binding of YBX1 to the Y-box sequence in the MDR1 promoter than the unacetylated form. Deacetylated on lysines. Lys-6 and Lys-7 are deacetylated by SIRT1.3 Publications
    Cleaved at Lys-31 by granzyme A to create the mitochondrial form; leading in reduction of binding to DNA, AP endodeoxynuclease activity, redox activation of transcription factors and to enhanced cell death. Cleaved by granzyme K; leading to intracellular ROS accumulation and enhanced cell death after oxidative stress.
    Cys-65 and Cys-93 are nitrosylated in response to nitric oxide (NO) and lead to the exposure of the nuclear export signal (NES).1 Publication
    Ubiquitinated by MDM2; leading to translocation to the cytoplasm and proteasomal degradation.1 Publication

    Keywords - PTMi

    Acetylation, Cleavage on pair of basic residues, Disulfide bond, Phosphoprotein, S-nitrosylation, Ubl conjugation

    Proteomic databases

    MaxQBiP27695.
    PaxDbiP27695.
    PeptideAtlasiP27695.
    PRIDEiP27695.

    PTM databases

    PhosphoSiteiP27695.

    Miscellaneous databases

    PMAP-CutDBP27695.

    Expressioni

    Inductioni

    Up-regulated in presence of reactive oxygen species (ROS), like bleomycin, H2O2 and phenazine methosulfate.1 Publication

    Gene expression databases

    ArrayExpressiP27695.
    BgeeiP27695.
    CleanExiHS_APEX1.
    HS_HAP1.
    GenevestigatoriP27695.

    Organism-specific databases

    HPAiCAB004294.
    CAB047307.
    HPA000956.
    HPA002564.

    Interactioni

    Subunit structurei

    Monomer. Homodimer; disulfide-linked. Component of the SET complex, composed of at least APEX1, SET, ANP32A, HMGB2, NME1 and TREX1. Associates with the dimer XRCC5/XRCC6 in a DNA-dependent manner. Interacts with SIRT1; the interaction is increased in the context of genotoxic stress. Interacts with HDAC1, HDAC2 and HDAC3; the interactions are not dependent on the APEX1 acetylation status. Interacts with XRCC1; the interaction is induced by SIRT1 and increased with the APEX1 acetylated form. Interacts with NPM1 (via N-terminal domain); the interaction is RNA-dependent and decreases in hydrogen peroxide-damaged cells. Interacts (via N-terminus) with YBX1 (via C-terminus); the interaction is increased in presence of APEX1 acetylated at Lys-6 and Lys-7. Interacts with HNRNPL; the interaction is DNA-dependent. Interacts (via N-terminus) with KPNA1 and KPNA2. Interacts with TXN; the interaction stimulates the FOS/JUN AP-1 complex DNA-binding activity in a redox-dependent manner. Interacts with GZMA, KRT8, MDM2, POLB, PRDX6, PRPF19, RPLP0, TOMM20 and WDR77. Binds to CDK5.17 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    EP300Q094728EBI-1048805,EBI-447295
    SIRT1Q96EB66EBI-1048805,EBI-1802965

    Protein-protein interaction databases

    BioGridi106825. 66 interactions.
    DIPiDIP-6130N.
    IntActiP27695. 29 interactions.
    MINTiMINT-119189.
    STRINGi9606.ENSP00000216714.

    Structurei

    Secondary structure

    1
    318
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi62 – 687
    Helixi72 – 776
    Helixi80 – 878
    Beta strandi90 – 956
    Helixi101 – 1033
    Helixi106 – 1105
    Helixi112 – 1143
    Beta strandi116 – 1205
    Beta strandi122 – 1243
    Beta strandi126 – 1283
    Beta strandi131 – 1377
    Beta strandi140 – 1456
    Helixi149 – 1513
    Beta strandi152 – 1543
    Beta strandi157 – 1615
    Beta strandi166 – 1716
    Helixi177 – 1793
    Helixi182 – 20019
    Beta strandi205 – 2106
    Helixi217 – 2193
    Turni223 – 2253
    Beta strandi227 – 2293
    Turni230 – 2323
    Helixi234 – 24613
    Beta strandi249 – 2513
    Helixi252 – 2565
    Beta strandi257 – 2593
    Helixi270 – 2723
    Helixi273 – 2764
    Beta strandi283 – 2875
    Helixi289 – 2946
    Beta strandi295 – 3006
    Beta strandi306 – 3094
    Beta strandi312 – 3165

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1BIXX-ray2.20A32-318[»]
    1CQGNMR-B59-71[»]
    1CQHNMR-B59-71[»]
    1DE8X-ray2.95A/B43-318[»]
    1DE9X-ray3.00A/B43-318[»]
    1DEWX-ray2.65A/B40-318[»]
    1E9NX-ray2.20A/B2-318[»]
    1HD7X-ray1.95A2-318[»]
    2ISIX-ray2.76A/B/C2-318[»]
    2O3HX-ray1.90A40-318[»]
    3U8UX-ray2.15A/B/C/D/E/F1-318[»]
    4IEMX-ray2.39A/B/C/D2-318[»]
    4LNDX-ray1.92A/B/C39-318[»]
    DisProtiDP00007.
    ProteinModelPortaliP27695.
    SMRiP27695. Positions 44-318.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP27695.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni2 – 3332Necessary for interaction with YBX1, binding to RNA, NPM1-dependent association with rRNA, endoribonuclease activity on abasic RNA and localization in the nucleoliAdd
    BLAST
    Regioni8 – 136Nuclear localization signal (NLS)
    Regioni23 – 3311Necessary for interaction with NPM1 and for efficient rRNA bindingAdd
    BLAST
    Regioni64 – 8017Nuclear export signal (NES)Add
    BLAST
    Regioni289 – 31830Mitochondrial targeting sequence (MTS)Add
    BLAST

    Domaini

    The N-terminus contains the redox activity while the C-terminus exerts the DNA AP-endodeoxyribonuclease activity; both function are independent in their actions. An unconventional mitochondrial targeting sequence (MTS) is harbored within the C-terminus, that appears to be masked by the N-terminal sequence containing the nuclear localization signal (NLS), that probably blocks the interaction between the MTS and Tom proteins.

    Sequence similaritiesi

    Belongs to the DNA repair enzymes AP/ExoA family.Curated

    Phylogenomic databases

    eggNOGiCOG0708.
    HOGENOMiHOG000034586.
    HOVERGENiHBG050531.
    InParanoidiP27695.
    KOiK10771.
    OMAiTCTSCEV.
    OrthoDBiEOG7C8GJ6.
    PhylomeDBiP27695.
    TreeFamiTF315048.

    Family and domain databases

    Gene3Di3.60.10.10. 1 hit.
    InterProiIPR004808. AP_endonuc_1.
    IPR020847. AP_endonuclease_F1_BS.
    IPR020848. AP_endonuclease_F1_CS.
    IPR005135. Endo/exonuclease/phosphatase.
    [Graphical view]
    PANTHERiPTHR22748. PTHR22748. 1 hit.
    PfamiPF03372. Exo_endo_phos. 1 hit.
    [Graphical view]
    SUPFAMiSSF56219. SSF56219. 1 hit.
    TIGRFAMsiTIGR00633. xth. 1 hit.
    PROSITEiPS00726. AP_NUCLEASE_F1_1. 1 hit.
    PS00727. AP_NUCLEASE_F1_2. 1 hit.
    PS00728. AP_NUCLEASE_F1_3. 1 hit.
    PS51435. AP_NUCLEASE_F1_4. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P27695-1 [UniParc]FASTAAdd to Basket

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    MPKRGKKGAV AEDGDELRTE PEAKKSKTAA KKNDKEAAGE GPALYEDPPD    50
    QKTSPSGKPA TLKICSWNVD GLRAWIKKKG LDWVKEEAPD ILCLQETKCS 100
    ENKLPAELQE LPGLSHQYWS APSDKEGYSG VGLLSRQCPL KVSYGIGDEE 150
    HDQEGRVIVA EFDSFVLVTA YVPNAGRGLV RLEYRQRWDE AFRKFLKGLA 200
    SRKPLVLCGD LNVAHEEIDL RNPKGNKKNA GFTPQERQGF GELLQAVPLA 250
    DSFRHLYPNT PYAYTFWTYM MNARSKNVGW RLDYFLLSHS LLPALCDSKI 300
    RSKALGSDHC PITLYLAL 318
    Length:318
    Mass (Da):35,555
    Last modified:January 23, 2007 - v2
    Checksum:iB88579C01BAF80C6
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti57 – 571G → A in AAA58371. (PubMed:1722334)Curated
    Sequence conflicti306 – 3061G → A in AAA58371. (PubMed:1722334)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti51 – 511Q → H.1 Publication
    Corresponds to variant rs1048945 [ dbSNP | Ensembl ].
    VAR_013455
    Natural varianti64 – 641I → V.1 Publication
    Corresponds to variant rs2307486 [ dbSNP | Ensembl ].
    VAR_014823
    Natural varianti148 – 1481D → E.2 Publications
    Corresponds to variant rs1130409 [ dbSNP | Ensembl ].
    VAR_019790

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X59764 mRNA. Translation: CAA42437.1.
    M80261 mRNA. Translation: AAA58371.1.
    D90373 mRNA. Translation: BAA14381.1.
    S43127 mRNA. Translation: AAB22977.1.
    M81955 mRNA. Translation: AAA58372.1.
    M92444 Genomic DNA. Translation: AAA58629.1.
    X66133 Genomic DNA. Translation: CAA46925.1.
    D13370 Genomic DNA. Translation: BAA02633.1.
    U79268 mRNA. Translation: AAB50212.1.
    BT007236 mRNA. Translation: AAP35900.1.
    AF488551 Genomic DNA. Translation: AAL86909.1.
    AL355075 Genomic DNA. No translation available.
    BC002338 mRNA. Translation: AAH02338.1.
    BC004979 mRNA. Translation: AAH04979.1.
    BC008145 mRNA. Translation: AAH08145.1.
    BC019291 mRNA. Translation: AAH19291.1.
    M99703 Genomic DNA. Translation: AAA58373.1.
    CCDSiCCDS9550.1.
    PIRiS23550.
    RefSeqiNP_001231178.1. NM_001244249.1.
    NP_001632.2. NM_001641.3.
    NP_542379.1. NM_080648.2.
    NP_542380.1. NM_080649.2.
    XP_005267638.1. XM_005267581.2.
    UniGeneiHs.73722.

    Genome annotation databases

    EnsembliENST00000216714; ENSP00000216714; ENSG00000100823.
    ENST00000398030; ENSP00000381111; ENSG00000100823.
    ENST00000555414; ENSP00000451979; ENSG00000100823.
    ENST00000557344; ENSP00000452137; ENSG00000100823.
    GeneIDi328.
    KEGGihsa:328.
    UCSCiuc001vxg.3. human.

    Polymorphism databases

    DMDMi113984.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X59764 mRNA. Translation: CAA42437.1 .
    M80261 mRNA. Translation: AAA58371.1 .
    D90373 mRNA. Translation: BAA14381.1 .
    S43127 mRNA. Translation: AAB22977.1 .
    M81955 mRNA. Translation: AAA58372.1 .
    M92444 Genomic DNA. Translation: AAA58629.1 .
    X66133 Genomic DNA. Translation: CAA46925.1 .
    D13370 Genomic DNA. Translation: BAA02633.1 .
    U79268 mRNA. Translation: AAB50212.1 .
    BT007236 mRNA. Translation: AAP35900.1 .
    AF488551 Genomic DNA. Translation: AAL86909.1 .
    AL355075 Genomic DNA. No translation available.
    BC002338 mRNA. Translation: AAH02338.1 .
    BC004979 mRNA. Translation: AAH04979.1 .
    BC008145 mRNA. Translation: AAH08145.1 .
    BC019291 mRNA. Translation: AAH19291.1 .
    M99703 Genomic DNA. Translation: AAA58373.1 .
    CCDSi CCDS9550.1.
    PIRi S23550.
    RefSeqi NP_001231178.1. NM_001244249.1.
    NP_001632.2. NM_001641.3.
    NP_542379.1. NM_080648.2.
    NP_542380.1. NM_080649.2.
    XP_005267638.1. XM_005267581.2.
    UniGenei Hs.73722.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1BIX X-ray 2.20 A 32-318 [» ]
    1CQG NMR - B 59-71 [» ]
    1CQH NMR - B 59-71 [» ]
    1DE8 X-ray 2.95 A/B 43-318 [» ]
    1DE9 X-ray 3.00 A/B 43-318 [» ]
    1DEW X-ray 2.65 A/B 40-318 [» ]
    1E9N X-ray 2.20 A/B 2-318 [» ]
    1HD7 X-ray 1.95 A 2-318 [» ]
    2ISI X-ray 2.76 A/B/C 2-318 [» ]
    2O3H X-ray 1.90 A 40-318 [» ]
    3U8U X-ray 2.15 A/B/C/D/E/F 1-318 [» ]
    4IEM X-ray 2.39 A/B/C/D 2-318 [» ]
    4LND X-ray 1.92 A/B/C 39-318 [» ]
    DisProti DP00007.
    ProteinModelPortali P27695.
    SMRi P27695. Positions 44-318.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 106825. 66 interactions.
    DIPi DIP-6130N.
    IntActi P27695. 29 interactions.
    MINTi MINT-119189.
    STRINGi 9606.ENSP00000216714.

    Chemistry

    BindingDBi P27695.
    ChEMBLi CHEMBL5619.
    DrugBanki DB04967. Lucanthone.

    PTM databases

    PhosphoSitei P27695.

    Polymorphism databases

    DMDMi 113984.

    Proteomic databases

    MaxQBi P27695.
    PaxDbi P27695.
    PeptideAtlasi P27695.
    PRIDEi P27695.

    Protocols and materials databases

    DNASUi 328.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000216714 ; ENSP00000216714 ; ENSG00000100823 .
    ENST00000398030 ; ENSP00000381111 ; ENSG00000100823 .
    ENST00000555414 ; ENSP00000451979 ; ENSG00000100823 .
    ENST00000557344 ; ENSP00000452137 ; ENSG00000100823 .
    GeneIDi 328.
    KEGGi hsa:328.
    UCSCi uc001vxg.3. human.

    Organism-specific databases

    CTDi 328.
    GeneCardsi GC14P020924.
    HGNCi HGNC:587. APEX1.
    HPAi CAB004294.
    CAB047307.
    HPA000956.
    HPA002564.
    MIMi 107748. gene.
    neXtProti NX_P27695.
    PharmGKBi PA201059.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0708.
    HOGENOMi HOG000034586.
    HOVERGENi HBG050531.
    InParanoidi P27695.
    KOi K10771.
    OMAi TCTSCEV.
    OrthoDBi EOG7C8GJ6.
    PhylomeDBi P27695.
    TreeFami TF315048.

    Enzyme and pathway databases

    BRENDAi 4.2.99.18. 2681.
    Reactomei REACT_1064. Displacement of DNA glycosylase by APE1.
    REACT_1128. Resolution of AP sites via the multiple-nucleotide patch replacement pathway.
    REACT_1357. Base-free sugar-phosphate removal via the single-nucleotide replacement pathway.
    REACT_2192. Removal of DNA patch containing abasic residue.

    Miscellaneous databases

    ChiTaRSi APEX1. human.
    EvolutionaryTracei P27695.
    GeneWikii APEX1.
    GenomeRNAii 328.
    NextBioi 1347.
    PMAP-CutDB P27695.
    PROi P27695.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P27695.
    Bgeei P27695.
    CleanExi HS_APEX1.
    HS_HAP1.
    Genevestigatori P27695.

    Family and domain databases

    Gene3Di 3.60.10.10. 1 hit.
    InterProi IPR004808. AP_endonuc_1.
    IPR020847. AP_endonuclease_F1_BS.
    IPR020848. AP_endonuclease_F1_CS.
    IPR005135. Endo/exonuclease/phosphatase.
    [Graphical view ]
    PANTHERi PTHR22748. PTHR22748. 1 hit.
    Pfami PF03372. Exo_endo_phos. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56219. SSF56219. 1 hit.
    TIGRFAMsi TIGR00633. xth. 1 hit.
    PROSITEi PS00726. AP_NUCLEASE_F1_1. 1 hit.
    PS00727. AP_NUCLEASE_F1_2. 1 hit.
    PS00728. AP_NUCLEASE_F1_3. 1 hit.
    PS51435. AP_NUCLEASE_F1_4. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Isolation of cDNA clones encoding a human apurinic/apyrimidinic endonuclease that corrects DNA repair and mutagenesis defects in E. coli xth (exonuclease III) mutants."
      Robson C.N., Hickson I.D.
      Nucleic Acids Res. 19:5519-5523(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
      Tissue: Melanocyte.
    2. "Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: definition of a family of DNA repair enzymes."
      Demple B., Herman T., Chen D.S.
      Proc. Natl. Acad. Sci. U.S.A. 88:11450-11454(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Placenta.
    3. "cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III."
      Seki S., Hatsushika M., Watanabe S., Akiyama K., Nagao K., Tsutsui K.
      Biochim. Biophys. Acta 1131:287-299(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
      Tissue: Bone marrow and Leukocyte.
    4. "Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme."
      Xanthoudakis S., Miao G., Wang F., Pan Y.-C.E., Curran T.
      EMBO J. 11:3323-3335(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-21.
    5. "Nucleotide sequence of a cDNA for an apurinic/apyrimidinic endonuclease from HeLa cells."
      Cheng X.B., Bunville J., Patterson T.A.
      Nucleic Acids Res. 20:370-370(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Carcinoma.
    6. "The human gene for apurinic/apyrimidinic endonuclease (HAP1): sequence and localization to chromosome 14 band q12."
      Zhao B., Grandy D.K., Hagerup J.M., Magenis R.E., Smith L., Chauhan B.C., Henner W.D.
      Nucleic Acids Res. 20:4097-4098(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Leukocyte.
    7. "Structure of the human DNA repair gene HAP1 and its localisation to chromosome 14q 11.2-12."
      Robson C.N., Hocchauser D., Craig R., Rack K., Buckle I.D., Hickson I.D.
      Nucleic Acids Res. 20:4417-4421(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    8. "Structure, promoter analysis and chromosomal assignment of the human APEX gene."
      Akiyama K., Seki S., Oshida T., Yoshida M.
      Biochim. Biophys. Acta 1219:15-25(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    9. "Large-scale concatenation cDNA sequencing."
      Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W., Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A.
      Genome Res. 7:353-358(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain.
    10. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    11. NIEHS SNPs program
      Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-51; VAL-64 AND GLU-148.
    12. "The DNA sequence and analysis of human chromosome 14."
      Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H.
      , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
      Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    13. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLU-148.
      Tissue: Brain, Lung and Skin.
    14. "Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A."
      Fan Z., Beresford P.J., Zhang D., Xu Z., Novina C.D., Yoshida A., Pommier Y., Lieberman J.
      Nat. Immunol. 4:145-153(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-10, FUNCTION, INTERACTION WITH GZMA, CLEAVAGE BY GRANZYME A, IDENTIFICATION IN THE SET COMPLEX, MUTAGENESIS OF LYS-31; CYS-65 AND ASP-210, SUBCELLULAR LOCATION.
    15. "Human apurinic endonuclease gene (APE): structure and genomic mapping (chromosome 14q11.2-12)."
      Harrison L., Ascione G., Menninger J.C., Ward D.C., Demple B.
      Hum. Mol. Genet. 1:677-680(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-146.
      Tissue: Placenta.
    16. "Identification of residues in the human DNA repair enzyme HAP1 (Ref-1) that are essential for redox regulation of Jun DNA binding."
      Walker L.J., Robson C.N., Black E., Gillespie D., Hickson I.D.
      Mol. Cell. Biol. 13:5370-5376(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF CYS-65; CYS-93; CYS-99; CYS-138; CYS-208; CYS-296 AND CYS-310.
    17. "The interaction between Ku antigen and REF1 protein mediates negative gene regulation by extracellular calcium."
      Chung U., Igarashi T., Nishishita T., Iwanari H., Iwamatsu A., Suwa A., Mimori T., Hata K., Ebisu S., Ogata E., Fujita T., Okazaki T.
      J. Biol. Chem. 271:8593-8598(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH XRCC5 AND XRCC6.
    18. "Asparagine 212 is essential for abasic site recognition by the human DNA repair endonuclease HAP1."
      Rothwell D.G., Hickson I.D.
      Nucleic Acids Res. 24:4217-4221(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF ASN-212.
    19. "AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1."
      Hirota K., Matsui M., Iwata S., Nishiyama A., Mori K., Yodoi J.
      Proc. Natl. Acad. Sci. U.S.A. 94:3633-3638(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT, INTERACTION WITH TXN, SUBCELLULAR LOCATION.
    20. "Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway."
      Bennett R.A., Wilson D.M. III, Wong D., Demple B.
      Proc. Natl. Acad. Sci. U.S.A. 94:7166-7169(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH POLB.
    21. "Rapid dissociation of human apurinic endonuclease (Ape1) from incised DNA induced by magnesium."
      Masuda Y., Bennett R.A., Demple B.
      J. Biol. Chem. 273:30360-30365(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF ASP-283; ASP-308 AND HIS-309, COFACTOR.
    22. "Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species and its correlation with their adaptive response to genotoxicity of free radicals."
      Ramana C.V., Boldogh I., Izumi T., Mitra S.
      Proc. Natl. Acad. Sci. U.S.A. 95:5061-5066(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INDUCTION, SUBCELLULAR LOCATION.
    23. "Phosphorylation of the DNA repair protein APE/REF-1 by CKII affects redox regulation of AP-1."
      Fritz G., Kaina B.
      Oncogene 18:1033-1040(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION BY CKII, SUBCELLULAR LOCATION.
    24. "Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation."
      Wei S.J., Botero A., Hirota K., Bradbury C.M., Markovina S., Laszlo A., Spitz D.R., Goswami P.C., Yodoi J., Gius D.
      Cancer Res. 60:6688-6695(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    25. "Activation of APE/Ref-1 redox activity is mediated by reactive oxygen species and PKC phosphorylation."
      Hsieh M.M., Hegde V., Kelley M.R., Deutsch W.A.
      Nucleic Acids Res. 29:3116-3122(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION BY PKC.
    26. "HMG2 interacts with the nucleosome assembly protein SET and is a target of the cytotoxic T-lymphocyte protease granzyme A."
      Fan Z., Beresford P.J., Zhang D., Lieberman J.
      Mol. Cell. Biol. 22:2810-2820(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN THE SET COMPLEX.
    27. "An exonucleolytic activity of human apurinic/apyrimidinic endonuclease on 3' mispaired DNA."
      Chou K.M., Cheng Y.C.
      Nature 415:655-659(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    28. "Human AP-endonuclease 1 and hnRNP-L interact with a nCaRE-like repressor element in the AP-endonuclease 1 promoter."
      Kuninger D.T., Izumi T., Papaconstantinou J., Mitra S.
      Nucleic Acids Res. 30:823-829(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH HNRNPL.
    29. "Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation of the parathyroid hormone gene."
      Bhakat K.K., Izumi T., Yang S.H., Hazra T.K., Mitra S.
      EMBO J. 22:6299-6309(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HDAC1; HDAC2 AND HDAC3, ACETYLATION AT LYS-6 AND LYS-7, MUTAGENESIS OF LYS-6 AND LYS-7.
    30. "Novel role of tyrosine in catalysis by human AP endonuclease 1."
      Mundle S.T., Fattal M.H., Melo L.F., Coriolan J.D., O'Regan N.E., Strauss P.R.
      DNA Repair 3:1447-1455(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, ACTIVE SITE, MUTAGENESIS OF TYR-171.
    31. "Analysis of nuclear transport signals in the human apurinic/apyrimidinic endonuclease (APE1/Ref1)."
      Jackson E.B., Theriot C.A., Chattopadhyay R., Mitra S., Izumi T.
      Nucleic Acids Res. 33:3303-3312(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH KPNA1 AND KPNA2, MUTAGENESIS OF LYS-6; LYS-7; GLU-12 AND ASP-13, SUBCELLULAR LOCATION.
    32. "Identification and characterization of mitochondrial abasic (AP)-endonuclease in mammalian cells."
      Chattopadhyay R., Wiederhold L., Szczesny B., Boldogh I., Hazra T.K., Izumi T., Mitra S.
      Nucleic Acids Res. 34:2067-2076(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    33. "UVA irradiation induces relocalisation of the DNA repair protein hOGG1 to nuclear speckles."
      Campalans A., Amouroux R., Bravard A., Epe B., Radicella J.P.
      J. Cell Sci. 120:23-32(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    34. "Nitric oxide controls nuclear export of APE1/Ref-1 through S-nitrosation of cysteines 93 and 310."
      Qu J., Liu G.H., Huang B., Chen C.
      Nucleic Acids Res. 35:2522-2532(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: S-NITROSYLATION AT CYS-65; CYS-93 AND CYS-310 IN RESPONSE TO NITRIC OXIDE, SUBCELLULAR LOCATION.
    35. "Characterization of abasic endonuclease activity of human Ape1 on alternative substrates, as well as effects of ATP and sequence context on AP site incision."
      Berquist B.R., McNeill D.R., Wilson D.M. III
      J. Mol. Biol. 379:17-27(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    36. "Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-1-mediated activation of the multidrug resistance gene MDR1."
      Chattopadhyay R., Das S., Maiti A.K., Boldogh I., Xie J., Hazra T.K., Kohno K., Mitra S., Bhakat K.K.
      Mol. Cell. Biol. 28:7066-7080(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH MVP AND YBX1, MUTAGENESIS OF LYS-6 AND LYS-7, SUBCELLULAR LOCATION.
    37. "Granzyme K degrades the redox/DNA repair enzyme Ape1 to trigger oxidative stress of target cells leading to cytotoxicity."
      Guo Y., Chen J., Zhao T., Fan Z.
      Mol. Immunol. 45:2225-2235(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    38. "Evolution of the redox function in mammalian apurinic/apyrimidinic endonuclease."
      Georgiadis M.M., Luo M., Gaur R.K., Delaplane S., Li X., Kelley M.R.
      Mutat. Res. 643:54-63(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF CYS-65; CYS-93; CYS-99; CYS-138; CYS-208; CYS-296 AND CYS-310.
    39. "Enzymatic mechanism of human apurinic/apyrimidinic endonuclease against a THF AP site model substrate."
      Mundle S.T., Delaney J.C., Essigmann J.M., Strauss P.R.
      Biochemistry 48:19-26(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, COFACTOR, ENZYME MECHANISM.
    40. "APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process."
      Vascotto C., Fantini D., Romanello M., Cesaratto L., Deganuto M., Leonardi A., Radicella J.P., Kelley M.R., D'Ambrosio C., Scaloni A., Quadrifoglio F., Tell G.
      Mol. Cell. Biol. 29:1834-1854(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH KRT8; NPM1; PRDX6; PRPF19; RPLP0 AND WDR77, RNA-BINDING, SUBCELLULAR LOCATION.
    41. "Identification of apurinic/apyrimidinic endonuclease 1 (APE1) as the endoribonuclease that cleaves c-myc mRNA."
      Barnes T., Kim W.C., Mantha A.K., Kim S.E., Izumi T., Mitra S., Lee C.H.
      Nucleic Acids Res. 37:3946-3958(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, RNA-BINDING, MUTAGENESIS OF GLU-96 AND HIS-309.
    42. "Ubiquitination of mammalian AP endonuclease (APE1) regulated by the p53-MDM2 signaling pathway."
      Busso C.S., Iwakuma T., Izumi T.
      Oncogene 28:1616-1625(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MDM2, UBIQUITINATION, MUTAGENESIS OF LYS-24; LYS-25 AND LYS-27.
    43. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
      Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
      Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-197, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    44. "Identification and characterization of mitochondrial targeting sequence of human apurinic/apyrimidinic endonuclease 1."
      Li M., Zhong Z., Zhu J., Xiang D., Dai N., Cao X., Qing Y., Yang Z., Xie J., Li Z., Baugh L., Wang G., Wang D.
      J. Biol. Chem. 285:14871-14881(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TOMM20, MUTAGENESIS OF LYS-24; LYS-25; LYS-27; LYS-31; LYS-299; ARG-301 AND LYS-303, SUBCELLULAR LOCATION.
    45. Cited for: FUNCTION, INTERACTION WITH SIRT1 AND XRCC1, MUTAGENESIS OF LYS-6 AND LYS-7, SUBCELLULAR LOCATION.
    46. "Critical lysine residues within the overlooked N-terminal domain of human APE1 regulate its biological functions."
      Fantini D., Vascotto C., Marasco D., D'Ambrosio C., Romanello M., Vitagliano L., Pedone C., Poletto M., Cesaratto L., Quadrifoglio F., Scaloni A., Radicella J.P., Tell G.
      Nucleic Acids Res. 38:8239-8256(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH NPM1, RNA-BINDING, ACETYLATION AT LYS-27; LYS-31; LYS-32 AND LYS-35, MUTAGENESIS OF LYS-24; LYS-25; LYS-27; LYS-31 AND LYS-32, IDENTIFICATION BY MASS SPECTROMETRY.
    47. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    48. "Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain."
      Guo J.U., Su Y., Zhong C., Ming G.L., Song H.
      Cell 145:423-434(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DNA DEMETHYLATION.
    49. "Characterization of the endoribonuclease active site of human apurinic/apyrimidinic endonuclease 1."
      Kim W.C., Berquist B.R., Chohan M., Uy C., Wilson D.M. III, Lee C.H.
      J. Mol. Biol. 411:960-971(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF ASN-68; ASP-70; TYR-171; PHE-266; ASP-283; ASP-308 AND HIS-309, CATALYTIC ACTIVITY, ACTIVE SITE, FUNCTION, COFACTOR.
    50. "The crystal structure of the human DNA repair endonuclease HAP1 suggests the recognition of extra-helical deoxyribose at DNA abasic sites."
      Gorman M.A., Morera S., Rothwell D.G., de La Fortelle E., Mol C.D., Tainer J.A., Hickson I.D., Freemont P.S.
      EMBO J. 16:6548-6558(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 32-318 IN COMPLEX WITH METAL IONS.
    51. "DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination."
      Mol C.D., Izumi T., Mitra S., Tainer J.A.
      Nature 403:451-456(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 40-318 IN COMPLEX WITH DNA AND METAL ION, DNA-BINDING.
    52. "Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic mechanism."
      Beernink P.T., Segelke B.W., Hadi M.Z., Erzberger J.P., Wilson D.M. III, Rupp B.
      J. Mol. Biol. 307:1023-1034(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH METAL IONS, CATALYTIC ACTIVITY, COFACTOR.

    Entry informationi

    Entry nameiAPEX1_HUMAN
    AccessioniPrimary (citable) accession number: P27695
    Secondary accession number(s): Q969L5, Q99775
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 185 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    Extract of mitochondria, but not of nuclei or cytosol, cleaves recombinant APEX1 to generate a mitochondrial APEX1-sized product By similarity. The specific activity of the cleaved mitochondrial endodeoxyribonuclease appeared to be about 3-fold higher than that of the full-length form.By similarity

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 14
      Human chromosome 14: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3