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P27695

- APEX1_HUMAN

UniProt

P27695 - APEX1_HUMAN

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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

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. RNA-DNA hybrid ribonuclease activity Source: UniProtKB
  15. site-specific endodeoxyribonuclease activity, specific for altered base Source: UniProtKB
  16. transcription coactivator activity Source: UniProtKB
  17. transcription corepressor activity Source: ProtInc
  18. 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
Complete GO annotation...

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
Complete GO annotation...

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

BgeeiP27695.
CleanExiHS_APEX1.
HS_HAP1.
ExpressionAtlasiP27695. baseline and differential.
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. 70 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.
GeneTreeiENSGT00530000063540.
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

« Hide

        10         20         30         40         50
MPKRGKKGAV AEDGDELRTE PEAKKSKTAA KKNDKEAAGE GPALYEDPPD
60 70 80 90 100
QKTSPSGKPA TLKICSWNVD GLRAWIKKKG LDWVKEEAPD ILCLQETKCS
110 120 130 140 150
ENKLPAELQE LPGLSHQYWS APSDKEGYSG VGLLSRQCPL KVSYGIGDEE
160 170 180 190 200
HDQEGRVIVA EFDSFVLVTA YVPNAGRGLV RLEYRQRWDE AFRKFLKGLA
210 220 230 240 250
SRKPLVLCGD LNVAHEEIDL RNPKGNKKNA GFTPQERQGF GELLQAVPLA
260 270 280 290 300
DSFRHLYPNT PYAYTFWTYM MNARSKNVGW RLDYFLLSHS LLPALCDSKI
310
RSKALGSDHC PITLYLAL
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. 70 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.
GeneTreei ENSGT00530000063540.
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

Bgeei P27695.
CleanExi HS_APEX1.
HS_HAP1.
ExpressionAtlasi P27695. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 186 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