APEX1
entrez
328
canonical
uniprot
P27695
canonical
ensembl
ENSG00000100823
resolver
ensembl
ENSG00000291796
resolver
ensp
ENSP00000216714
resolver
ensp
ENSP00000381111
resolver
ensp
ENSP00000451979
resolver
ensp
ENSP00000517339
resolver
ensp
ENSP00000517342
resolver
ensp
ENSP00000517343
resolver
ensp
ENSP00000569674
resolver
ensp
ENSP00000569675
resolver
ensp
ENSP00000569676
resolver
ensp
ENSP00000606746
resolver
ensp
ENSP00000606749
resolver
ensp
ENSP00000606752
resolver
ensp
ENSP00000606754
resolver
ensp
ENSP00000626489
resolver
enst
ENST00000216714
resolver
enst
ENST00000398030
resolver
enst
ENST00000555414
resolver
enst
ENST00000708787
resolver
enst
ENST00000708794
resolver
enst
ENST00000708795
resolver
enst
ENST00000899615
resolver
enst
ENST00000899616
resolver
enst
ENST00000899617
resolver
enst
ENST00000936690
resolver
enst
ENST00000936693
resolver
enst
ENST00000936695
resolver
enst
ENST00000956430
resolver
genesymbol
APEX1
resolver
genesymbol_syn
APE
resolver
genesymbol_syn
APE1
resolver
genesymbol_syn
APEX
resolver
genesymbol_syn
APX
resolver
genesymbol_syn
HAP1
resolver
genesymbol_syn
REF1
resolver
hgnc
HGNC:587
resolver
uniprot
Q5TZP7
resolver
uniprot
Q969L5
resolver
uniprot
Q99775
resolver
uniprot_entry
APEX1_HUMAN
resolver
uniprot_entry
Q5TZP7_HUMAN
resolver
uniprot_sec
Q969L5
resolver
uniprot_sec
Q99775
resolver
activity_regulation
ACTIVITY REGULATION: NPM1 stimulates endodeoxyribonuclease activity on double-stranded DNA with AP sites, but inhibits endoribonuclease activity on single-stranded RNA containing AP sites. {ECO:0000269|PubMed:19188445}.
uniprot
proteins
amino_acid_sequence
MPKRGKKGAVAEDGDELRTEPEAKKSKTAAKKNDKEAAGEGPALYEDPPDQKTSPSGKPATLKICSWNVDGLRAWIKKKGLDWVKEEAPDILCLQETKCSENKLPAELQELPGLSHQYWSAPSDKEGYSGVGLLSRQCPLKVSYGIGDEEHDQEGRVIVAEFDSFVLVTAYVPNAGRGLVRLEYRQRWDEAFRKFLKGLASRKPLVLCGDLNVAHEEIDLRNPKGNKKNAGFTPQERQGFGELLQAVPLADSFRHLYPNTPYAYTFWTYMMNARSKNVGWRLDYFLLSHSLLPALCDSKIRSKALGSDHCPITLYLAL
uniprot
proteins
ec_number
3.1.11.2
uniprot
proteins
ec_number
3.1.21.-
uniprot
proteins
function
FUNCTION: Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 are DNA repair and redox regulation of transcriptional factors (PubMed:11118054, PubMed:11452037, PubMed:15831793, PubMed:18439621, PubMed:18579163, PubMed:21762700, PubMed:24079850, PubMed:8355688, PubMed:9108029, PubMed:9560228). Functions as an apurinic/apyrimidinic (AP) endodeoxyribonuclease in the 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. Also incises at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules (PubMed:15380100, PubMed:16617147, PubMed:18439621, PubMed:19123919, PubMed:19188445, PubMed:19934257, PubMed:20699270, PubMed:21762700, PubMed:24079850, PubMed:8932375, PubMed:8995436, PubMed:9804799). Operates at switch sites of immunoglobulin (Ig) constant regions where it mediates Ig isotype class switch recombination. Processes AP sites induced by successive action of AICDA and UNG. Generates staggered nicks in opposite DNA strands resulting in the formation of double-strand DNA breaks that are finally resolved via non-homologous end joining repair pathway (By similarity). Has 3'-5' exodeoxyribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER (PubMed:11832948, PubMed:1719477). Possesses DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate and 8-oxoguanine) blocking the 3' side of DNA strand breaks (PubMed:15831793, PubMed:7516064). Also acts 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 (PubMed:19188445, PubMed:19401441, PubMed:21762700). 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 (PubMed:9207062). 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 (PubMed:10023679, PubMed:11118054, PubMed:11452037, PubMed:18579163, PubMed:8355688, PubMed:9108029). 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 (PubMed:11809897, PubMed:14633989, PubMed:8621488). May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation (PubMed:21496894). Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance (PubMed:18809583). Plays a role in protection from granzyme-mediated cellular repair leading to cell death (PubMed:18179823). Binds DNA and RNA. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA (PubMed:19188445, PubMed:19401441, PubMed:20699270). {ECO:0000250|UniProtKB:P28352, ECO:0000269|PubMed:10023679, ECO:0000269|PubMed:11118054, ECO:0000269|PubMed:11452037, ECO:0000269|PubMed:11809897, ECO:0000269|PubMed:11832948, ECO:0000269|PubMed:12524539, ECO:0000269|PubMed:14633989, ECO:0000269|PubMed:15380100, ECO:0000269|PubMed:15831793, ECO:0000269|PubMed:16617147, ECO:0000269|PubMed:1719477, ECO:0000269|PubMed:18179823, ECO:0000269|PubMed:18439621, ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:18809583, ECO:0000269|PubMed:19123919, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:19401441, ECO:0000269|PubMed:19934257, ECO:0000269|PubMed:20699270, ECO:0000269|PubMed:21496894, ECO:0000269|PubMed:21762700, ECO:0000269|PubMed:24079850, ECO:0000269|PubMed:7516064, ECO:0000269|PubMed:8355688, ECO:0000269|PubMed:8621488, ECO:0000269|PubMed:8932375, ECO:0000269|PubMed:8995436, ECO:0000269|PubMed:9108029, ECO:0000269|PubMed:9207062, ECO:0000269|PubMed:9560228, ECO:0000269|PubMed:9804799}.
uniprot
proteins
mass_dalton
35555
uniprot
proteins
mutagenesis
MUTAGEN 6; /note="K->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."; /evidence="ECO:0000269|PubMed:14633989, ECO:0000269|PubMed:15942031, ECO:0000269|PubMed:18809583, ECO:0000269|PubMed:19934257"; MUTAGEN 7; /note="K->R: Lack of acetylation and does not stimulate the YBX1-mediated MDR1 promoter activity and alter nuclear subcellular localization; when associated with R-6."; /evidence="ECO:0000269|PubMed:14633989, ECO:0000269|PubMed:15942031, ECO:0000269|PubMed:18809583, ECO:0000269|PubMed:19934257"; MUTAGEN 12; /note="E->A: Reduces nuclear localization; when associated with A-13."; /evidence="ECO:0000269|PubMed:15942031"; MUTAGEN 13; /note="D->A: Reduces nuclear localization; when associated with A-12."; /evidence="ECO:0000269|PubMed:15942031"; MUTAGEN 24; /note="K->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."; /evidence="ECO:0000269|PubMed:19219073, ECO:0000269|PubMed:20231292, ECO:0000269|PubMed:20699270"; MUTAGEN 25; /note="K->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."; /evidence="ECO:0000269|PubMed:19219073, ECO:0000269|PubMed:20231292, ECO:0000269|PubMed:20699270"; MUTAGEN 27; /note="K->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."; /evidence="ECO:0000269|PubMed:19219073, ECO:0000269|PubMed:20231292, ECO:0000269|PubMed:20699270"; MUTAGEN 31; /note="K->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."; /evidence="ECO:0000269|PubMed:12524539, ECO:0000269|PubMed:20231292, ECO:0000269|PubMed:20699270"; MUTAGEN 32; /note="K->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."; /evidence="ECO:0000269|PubMed:20699270"; MUTAGEN 65; /note="C->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."; /evidence="ECO:0000269|PubMed:12524539, ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:8355688"; MUTAGEN 65; /note="C->S: Does not abolish NO-induced nitrosylation. Enhances NO-induced nuclear export."; /evidence="ECO:0000269|PubMed:12524539, ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:8355688"; MUTAGEN 68; /note="N->A: Nearly abolishes AP endodeoxyribonuclease activity."; /evidence="ECO:0000269|PubMed:21762700"; MUTAGEN 70; /note="D->A: Strongly reduces AP endodeoxyribonuclease activity."; /evidence="ECO:0000269|PubMed:21762700"; MUTAGEN 93; /note="C->A: Abolishes partially the redox activity."; /evidence="ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:8355688"; MUTAGEN 93; /note="C->S: Does not abolish NO-induced nitrosylation. Abolishes NO-induced nitrosylation and translocation from the nucleus to the cytoplasm; when associated with S-310."; /evidence="ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:8355688"; MUTAGEN 96; /note="E->A: Lacks MYCCRDRNA cleavage activity."; /evidence="ECO:0000269|PubMed:19401441"; MUTAGEN 99; /note="C->A: Does not abolish the redox activity."; /evidence="ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:8355688"; MUTAGEN 138; /note="C->A: Does not abolish the redox activity."; /evidence="ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:8355688"; MUTAGEN 171; /note="Y->A,F,H: Abolishes the AP endodeoxyribonuclease activity."; /evidence="ECO:0000269|PubMed:15380100, ECO:0000269|PubMed:21762700"; MUTAGEN 208; /note="C->A: Does not abolish the redox activity."; /evidence="ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:8355688"; MUTAGEN 210; /note="D->A,N: Abolishes the AP endodeoxyribonuclease activity. Reduces protection from granzyme A-mediated cell death; when associated with A-31 and A-65."; /evidence="ECO:0000269|PubMed:12524539"; MUTAGEN 212; /note="N->A: Abolishes AP endodeoxyribonuclease activity."; /evidence="ECO:0000269|PubMed:8932375"; MUTAGEN 212; /note="N->Q,D: Decreases AP endodeoxyribonuclease activity."; /evidence="ECO:0000269|PubMed:8932375"; MUTAGEN 266; /note="F->A: Strongly reduces AP endodeoxyribonuclease activity."; /evidence="ECO:0000269|PubMed:21762700"; MUTAGEN 283; /note="D->A: Strongly reduces AP endodeoxyribonuclease activity, but does not affect RNA cleavage activity. Nearly abolishes AP endodeoxyribonuclease activity; when associated with A-308."; /evidence="ECO:0000269|PubMed:21762700, ECO:0000269|PubMed:9804799"; MUTAGEN 296; /note="C->A: Does not abolish the redox activity."; /evidence="ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:8355688"; MUTAGEN 299; /note="K->A: Reduces the interaction with TOMM20. Abolishes localization in the mitochondria; when associated with A-301."; /evidence="ECO:0000269|PubMed:20231292"; MUTAGEN 301; /note="R->A: Reduces the interaction with TOMM20. Abolishes localization in the mitochondria; when associated with A-299."; /evidence="ECO:0000269|PubMed:20231292"; MUTAGEN 303; /note="K->A: Reduces the interaction with TOMM20."; /evidence="ECO:0000269|PubMed:20231292"; MUTAGEN 308; /note="D->A: Reduces AP endodeoxyribonuclease activity. Nearly abolishes AP endodeoxyribonuclease activity; when associated with A-283."; /evidence="ECO:0000269|PubMed:21762700, ECO:0000269|PubMed:9804799"; MUTAGEN 309; /note="H->N,S: Abolishes AP endodeoxyribonuclease activity. Lacks MYCCRDRNA cleavage activity."; /evidence="ECO:0000269|PubMed:19401441, ECO:0000269|PubMed:21762700, ECO:0000269|PubMed:9804799"; MUTAGEN 310; /note="C->A: Does not abolish the redox activity."; /evidence="ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:8355688"; MUTAGEN 310; /note="C->S: Does not abolish NO-induced nitrosylation. Abolishes NO-induced nitrosylation and translocation from the nucleus to the cytoplasm; when associated with S-93."; /evidence="ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:8355688
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000269|PubMed:10023679, ECO:0000269|PubMed:11452037}.; PTM: Acetylated on Lys-6 and Lys-7. Acetylation is increased by the transcriptional coactivator EP300 acetyltransferase, genotoxic agents like H(2)O(2) 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. {ECO:0000269|PubMed:14633989, ECO:0000269|PubMed:20699270}.; PTM: Cleaved at Lys-31 by granzyme A to create the mitochondrial form; leading to 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. {ECO:0000269|PubMed:12524539}.; PTM: Cys-65 and Cys-93 are nitrosylated in response to nitric oxide (NO) and lead to the exposure of the nuclear export signal (NES). {ECO:0000269|PubMed:17403694}.; PTM: Ubiquitinated by MDM2; leading to translocation to the cytoplasm and proteasomal degradation. {ECO:0000269|PubMed:19219073}.
uniprot
proteins
protein_family
DNA repair enzymes AP/ExoA family
uniprot
proteins
pubmed
10023679
uniprot
proteins
pubmed
10667800
uniprot
proteins
pubmed
11118054
uniprot
proteins
pubmed
11286553
uniprot
proteins
pubmed
11452037
uniprot
proteins
pubmed
11809897
uniprot
proteins
pubmed
11832948
uniprot
proteins
pubmed
11909973
uniprot
proteins
pubmed
12508121
uniprot
proteins
pubmed
12524539
uniprot
proteins
pubmed
1284593
uniprot
proteins
pubmed
1371347
uniprot
proteins
pubmed
1380454
uniprot
proteins
pubmed
1380694
uniprot
proteins
pubmed
1383925
uniprot
proteins
pubmed
14633989
uniprot
proteins
pubmed
15380100
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15831793
uniprot
proteins
pubmed
15942031
uniprot
proteins
pubmed
1627644
uniprot
proteins
pubmed
16617147
uniprot
proteins
pubmed
17148573
uniprot
proteins
pubmed
1719477
uniprot
proteins
pubmed
1722334
uniprot
proteins
pubmed
17403694
uniprot
proteins
pubmed
18179823
uniprot
proteins
pubmed
18439621
uniprot
proteins
pubmed
18579163
uniprot
proteins
pubmed
18809583
uniprot
proteins
pubmed
19123919
uniprot
proteins
pubmed
19188445
uniprot
proteins
pubmed
19219073
uniprot
proteins
pubmed
19401441
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19934257
uniprot
proteins
pubmed
20231292
uniprot
proteins
pubmed
20699270
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21496894
uniprot
proteins
pubmed
21762700
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24079850
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26760506
uniprot
proteins
pubmed
7516064
uniprot
proteins
pubmed
8086453
uniprot
proteins
pubmed
8355688
uniprot
proteins
pubmed
8621488
uniprot
proteins
pubmed
8932375
uniprot
proteins
pubmed
8995436
uniprot
proteins
pubmed
9108029
uniprot
proteins
pubmed
9110174
uniprot
proteins
pubmed
9207062
uniprot
proteins
pubmed
9351835
uniprot
proteins
pubmed
9560228
uniprot
proteins
pubmed
9804799
uniprot
proteins
sequence_length
318
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00764}. Nucleus, nucleolus. 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. {ECO:0000250}.; SUBCELLULAR LOCATION: [DNA repair nuclease/redox regulator APEX1, 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. {ECO:0000250}.
uniprot
proteins