UniProtKB - P27695 (APEX1_HUMAN)
DNA-(apurinic or apyrimidinic site) endonuclease
APEX1
Functioni
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. 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 PublicationsMiscellaneous
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 70 | Magnesium 1 | 1 | |
Metal bindingi | 96 | Magnesium 1 | 1 | |
Active sitei | 171 | 1 | ||
Active sitei | 210 | Proton donor/acceptor | 1 | |
Metal bindingi | 210 | Magnesium 2 | 1 | |
Metal bindingi | 212 | Magnesium 2 | 1 | |
Sitei | 212 | Transition state stabilizer | 1 | |
Sitei | 283 | Important for catalytic activity | 1 | |
Metal bindingi | 308 | Magnesium 1 | 1 |
GO - Molecular functioni
- 3'-5'-exodeoxyribonuclease activity Source: UniProtKB
- 3'-5' exonuclease activity Source: UniProtKB
- chromatin DNA binding Source: UniProtKB
- class II DNA-(apurinic or apyrimidinic site) endonuclease activity Source: UniProtKB
- damaged DNA binding Source: UniProtKB
- DNA-(abasic site) binding Source: UniProtKB
- DNA-(apurinic or apyrimidinic site) endonuclease activity Source: UniProtKB
- DNA binding Source: UniProtKB
- double-stranded DNA 3'-5' exodeoxyribonuclease activity Source: GO_Central
- double-stranded DNA exodeoxyribonuclease activity Source: BHF-UCL
- double-stranded telomeric DNA binding Source: BHF-UCL
- endodeoxyribonuclease activity Source: Reactome
- endonuclease activity Source: MGI
- metal ion binding Source: UniProtKB
- NF-kappaB binding Source: Ensembl
- oxidoreductase activity Source: UniProtKB
- phosphodiesterase activity, acting on 3'-phosphoglycolate-terminated DNA strands Source: UniProtKB
- phosphodiesterase I activity Source: UniProtKB
- phosphoric diester hydrolase activity Source: UniProtKB
- protein-containing complex binding Source: Ensembl
- RNA binding Source: UniProtKB
- RNA-DNA hybrid ribonuclease activity Source: UniProtKB
- site-specific endodeoxyribonuclease activity, specific for altered base Source: UniProtKB
- transcription coactivator activity Source: UniProtKB
- transcription corepressor activity Source: ProtInc
- uracil DNA N-glycosylase activity Source: ProtInc
GO - Biological processi
- aging Source: Ensembl
- base-excision repair Source: CAFA
- base-excision repair, gap-filling Source: Reactome
- cell redox homeostasis Source: Ensembl
- cellular response to cAMP Source: Ensembl
- cellular response to hydrogen peroxide Source: Ensembl
- cellular response to peptide hormone stimulus Source: Ensembl
- DNA catabolic process, endonucleolytic Source: UniProtKB
- DNA demethylation Source: UniProtKB
- DNA recombination Source: UniProtKB-KW
- DNA repair Source: UniProtKB
- negative regulation of smooth muscle cell migration Source: Ensembl
- positive regulation of G1/S transition of mitotic cell cycle Source: Ensembl
- positive regulation of transcription by RNA polymerase II Source: ARUK-UCL
- regulation of apoptotic process Source: UniProtKB
- regulation of mRNA stability Source: UniProtKB
- response to xenobiotic stimulus Source: Ensembl
- telomere maintenance Source: BHF-UCL
- telomere maintenance via base-excision repair Source: BHF-UCL
Keywordsi
Molecular function | Activator, DNA-binding, Endonuclease, Exonuclease, Hydrolase, Nuclease, Repressor, RNA-binding |
Biological process | DNA damage, DNA recombination, DNA repair, Transcription, Transcription regulation |
Ligand | Magnesium, Metal-binding |
Enzyme and pathway databases
BRENDAi | 4.2.99.18, 2681 |
PathwayCommonsi | P27695 |
Reactomei | R-HSA-110357, Displacement of DNA glycosylase by APEX1 R-HSA-110362, POLB-Dependent Long Patch Base Excision Repair R-HSA-110373, Resolution of AP sites via the multiple-nucleotide patch replacement pathway R-HSA-5651801, PCNA-Dependent Long Patch Base Excision Repair R-HSA-73930, Abasic sugar-phosphate removal via the single-nucleotide replacement pathway R-HSA-73933, Resolution of Abasic Sites (AP sites) |
SignaLinki | P27695 |
SIGNORi | P27695 |
Names & Taxonomyi
Protein namesi | Recommended name: DNA-(apurinic or apyrimidinic site) endonuclease (EC:3.1.-.-5 Publications)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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:587, APEX1 |
MIMi | 107748, gene |
neXtProti | NX_P27695 |
VEuPathDBi | HostDB:ENSG00000100823 |
Subcellular locationi
Cytoplasm and Cytosol
Nucleus
Endoplasmic reticulum
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
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
Cytoskeleton
- centrosome Source: HPA
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
Mitochondrion
- mitochondrion Source: UniProtKB
Nucleus
- nuclear speck Source: UniProtKB
- nucleolus Source: UniProtKB
- nucleoplasm Source: UniProtKB
- nucleus Source: UniProtKB
Other locations
- chromosome, telomeric region Source: BHF-UCL
- cytoplasm Source: UniProtKB
- perinuclear region of cytoplasm Source: UniProtKB
- ribosome Source: UniProtKB
- transcription regulator complex Source: Ensembl
Keywords - Cellular componenti
Cytoplasm, Endoplasmic reticulum, Mitochondrion, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 6 | 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. 4 Publications | 1 | |
Mutagenesisi | 7 | 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. 4 Publications | 1 | |
Mutagenesisi | 12 | E → A: Reduces nuclear localization; when associated with A-13. 1 Publication | 1 | |
Mutagenesisi | 13 | D → A: Reduces nuclear localization; when associated with A-12. 1 Publication | 1 | |
Mutagenesisi | 24 | 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. 3 Publications | 1 | |
Mutagenesisi | 25 | 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. 3 Publications | 1 | |
Mutagenesisi | 27 | 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. 3 Publications | 1 | |
Mutagenesisi | 31 | 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. 3 Publications | 1 | |
Mutagenesisi | 32 | 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. 1 Publication | 1 | |
Mutagenesisi | 65 | 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. 3 Publications | 1 | |
Mutagenesisi | 65 | C → S: Does not abolish NO-induced nitrosylation. Enhances NO-induced nuclear export. 3 Publications | 1 | |
Mutagenesisi | 68 | N → A: Nearly abolishes AP endodeoxyribonuclease activity. 1 Publication | 1 | |
Mutagenesisi | 70 | D → A: Strongly reduces AP endodeoxyribonuclease activity. 1 Publication | 1 | |
Mutagenesisi | 93 | C → A: Abolishes partially the redox activity. 2 Publications | 1 | |
Mutagenesisi | 93 | 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. 2 Publications | 1 | |
Mutagenesisi | 96 | E → A: Lacks MYC CRD RNA cleavage activity. 1 Publication | 1 | |
Mutagenesisi | 99 | C → A: Does not abolish the redox activity. 2 Publications | 1 | |
Mutagenesisi | 138 | C → A: Does not abolish the redox activity. 2 Publications | 1 | |
Mutagenesisi | 171 | Y → A, F or H: Abolishes the AP endodeoxyribonuclease activity. 2 Publications | 1 | |
Mutagenesisi | 208 | C → A: Does not abolish the redox activity. 2 Publications | 1 | |
Mutagenesisi | 210 | D → 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 | 1 | |
Mutagenesisi | 212 | N → A: Abolishes AP endodeoxyribonuclease activity. 1 Publication | 1 | |
Mutagenesisi | 212 | N → Q or D: Decreases AP endodeoxyribonuclease activity. 1 Publication | 1 | |
Mutagenesisi | 266 | F → A: Strongly reduces AP endodeoxyribonuclease activity. 1 Publication | 1 | |
Mutagenesisi | 283 | D → 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 | 1 | |
Mutagenesisi | 296 | C → A: Does not abolish the redox activity. 2 Publications | 1 | |
Mutagenesisi | 299 | K → A: Reduces the interaction with TOMM20. Abolishes localization in the mitochondria; when associated with A-301. 1 Publication | 1 | |
Mutagenesisi | 301 | R → A: Reduces the interaction with TOMM20. Abolishes localization in the mitochondria; when associated with A-299. 1 Publication | 1 | |
Mutagenesisi | 303 | K → A: Reduces the interaction with TOMM20. 1 Publication | 1 | |
Mutagenesisi | 308 | D → A: Reduces AP endodeoxyribonuclease activity. Nearly abolishes AP endodeoxyribonuclease activity; when associated with A-283. 2 Publications | 1 | |
Mutagenesisi | 309 | H → N or S: Abolishes AP endodeoxyribonuclease activity. Lacks MYC CRD RNA cleavage activity. 3 Publications | 1 | |
Mutagenesisi | 310 | C → A: Does not abolish the redox activity. 2 Publications | 1 | |
Mutagenesisi | 310 | 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. 2 Publications | 1 |
Organism-specific databases
DisGeNETi | 328 |
OpenTargetsi | ENSG00000100823 |
PharmGKBi | PA201059 |
Miscellaneous databases
Pharosi | P27695, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5619 |
DrugBanki | DB04967, Lucanthone |
DrugCentrali | P27695 |
Genetic variation databases
BioMutai | APEX1 |
DMDMi | 113984 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed2 Publications | |||
ChainiPRO_0000200010 | 2 – 318 | DNA-(apurinic or apyrimidinic site) endonucleaseAdd BLAST | 317 | |
ChainiPRO_0000402572 | 32 – 318 | DNA-(apurinic or apyrimidinic site) endonuclease, mitochondrialBy similarityAdd BLAST | 287 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 6 | N6-acetyllysine; by EP3001 Publication | 1 | |
Modified residuei | 7 | N6-acetyllysine; by EP3001 Publication | 1 | |
Modified residuei | 27 | N6-acetyllysine1 Publication | 1 | |
Modified residuei | 31 | N6-acetyllysine1 Publication | 1 | |
Modified residuei | 32 | N6-acetyllysine1 Publication | 1 | |
Modified residuei | 35 | N6-acetyllysine1 Publication | 1 | |
Modified residuei | 54 | PhosphoserineCombined sources | 1 | |
Disulfide bondi | 65 ↔ 93 | AlternateCurated | ||
Modified residuei | 65 | S-nitrosocysteine; alternate1 Publication | 1 | |
Modified residuei | 93 | S-nitrosocysteine; alternate1 Publication | 1 | |
Modified residuei | 197 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 233 | Phosphothreonine; by CDK5By similarity | 1 | |
Modified residuei | 310 | S-nitrosocysteine1 Publication | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 31 – 32 | Cleavage; by granzyme A | 2 |
Keywords - PTMi
Acetylation, Cleavage on pair of basic residues, Disulfide bond, Phosphoprotein, S-nitrosylation, Ubl conjugationProteomic databases
CPTACi | CPTAC-23 CPTAC-24 |
EPDi | P27695 |
jPOSTi | P27695 |
MassIVEi | P27695 |
PaxDbi | P27695 |
PeptideAtlasi | P27695 |
PRIDEi | P27695 |
ProteomicsDBi | 54406 |
TopDownProteomicsi | P27695 |
PTM databases
GlyGeni | P27695, 1 site, 2 O-linked glycans (1 site) |
iPTMneti | P27695 |
MetOSitei | P27695 |
PhosphoSitePlusi | P27695 |
SwissPalmi | P27695 |
Expressioni
Inductioni
Gene expression databases
Bgeei | ENSG00000100823, Expressed in subventricular zone (inner) (primate) and 242 other tissues |
ExpressionAtlasi | P27695, baseline and differential |
Genevisiblei | P27695, HS |
Organism-specific databases
HPAi | ENSG00000100823, Low tissue specificity |
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 PublicationsSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 309 | Interaction with DNA substrate | 1 |
Binary interactionsi
P27695
With | #Exp. | IntAct |
---|---|---|
EP300 [Q09472] | 8 | EBI-1048805,EBI-447295 |
NFE2L2 [Q16236] | 3 | EBI-1048805,EBI-2007911 |
SIRT1 [Q96EB6] | 6 | EBI-1048805,EBI-1802965 |
Rnf4 [O88846] from Rattus norvegicus. | 2 | EBI-1048805,EBI-7258907 |
GO - Molecular functioni
- NF-kappaB binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 106825, 1237 interactors |
CORUMi | P27695 |
DIPi | DIP-6130N |
IntActi | P27695, 54 interactors |
MINTi | P27695 |
STRINGi | 9606.ENSP00000216714 |
Chemistry databases
BindingDBi | P27695 |
Miscellaneous databases
RNActi | P27695, protein |
Structurei
Secondary structure
3D structure databases
BMRBi | P27695 |
SMRi | P27695 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P27695 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 60 | DisorderedSequence analysisAdd BLAST | 60 | |
Regioni | 2 – 33 | Necessary for interaction with YBX1, binding to RNA, NPM1-dependent association with rRNA, endoribonuclease activity on abasic RNA and localization in the nucleoli1 PublicationAdd BLAST | 32 | |
Regioni | 23 – 33 | Necessary for interaction with NPM1 and for efficient rRNA bindingAdd BLAST | 11 | |
Regioni | 289 – 318 | Mitochondrial targeting sequence (MTS)Add BLAST | 30 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 8 – 13 | Nuclear localization signal (NLS) | 6 | |
Motifi | 64 – 80 | Nuclear export signal (NES)Add BLAST | 17 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 1 – 41 | Basic and acidic residuesSequence analysisAdd BLAST | 41 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1294, Eukaryota |
GeneTreei | ENSGT00530000063540 |
HOGENOMi | CLU_027539_1_3_1 |
InParanoidi | P27695 |
OMAi | WRIDHIY |
OrthoDBi | 1105625at2759 |
PhylomeDBi | P27695 |
TreeFami | TF315048 |
Family and domain databases
DisProti | DP00007 |
Gene3Di | 3.60.10.10, 1 hit |
InterProi | View protein in InterPro IPR004808, AP_endonuc_1 IPR020847, AP_endonuclease_F1_BS IPR020848, AP_endonuclease_F1_CS IPR036691, Endo/exonu/phosph_ase_sf IPR005135, Endo/exonuclease/phosphatase |
PANTHERi | PTHR22748, PTHR22748, 1 hit |
Pfami | View protein in Pfam PF03372, Exo_endo_phos, 1 hit |
SUPFAMi | SSF56219, SSF56219, 1 hit |
TIGRFAMsi | TIGR00633, xth, 1 hit |
PROSITEi | View protein in PROSITE 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 |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 11 potential isoforms that are computationally mapped.Show allAlign All
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
Computationally mapped potential isoform sequencesi
There are 11 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketG3V5Q1 | G3V5Q1_HUMAN | DNA-(apurinic or apyrimidinic site)... | APEX1 | 242 | Annotation score: | ||
G3V3M6 | G3V3M6_HUMAN | DNA-(apurinic or apyrimidinic site)... | APEX1 | 263 | Annotation score: | ||
G3V359 | G3V359_HUMAN | DNA-(apurinic or apyrimidinic site)... | APEX1 | 172 | Annotation score: | ||
G3V3C7 | G3V3C7_HUMAN | DNA-(apurinic or apyrimidinic site)... | APEX1 | 174 | Annotation score: | ||
G3V5M0 | G3V5M0_HUMAN | DNA-(apurinic or apyrimidinic site)... | APEX1 | 162 | Annotation score: | ||
A0A0C4DGK8 | A0A0C4DGK8_HUMAN | DNA-(apurinic or apyrimidinic site)... | APEX1 | 146 | Annotation score: | ||
H7C4A8 | H7C4A8_HUMAN | DNA-(apurinic or apyrimidinic site)... | APEX1 | 150 | Annotation score: | ||
G3V5D9 | G3V5D9_HUMAN | DNA-(apurinic or apyrimidinic site)... | APEX1 | 107 | Annotation score: | ||
G3V2D9 | G3V2D9_HUMAN | DNA-(apurinic or apyrimidinic site)... | APEX1 | 49 | Annotation score: | ||
G3V3Y6 | G3V3Y6_HUMAN | DNA-(apurinic or apyrimidinic site)... | APEX1 | 41 | Annotation score: | ||
There is more potential isoformShow all |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 57 | G → A in AAA58371 (PubMed:1722334).Curated | 1 | |
Sequence conflicti | 306 | G → A in AAA58371 (PubMed:1722334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_013455 | 51 | Q → H1 PublicationCorresponds to variant dbSNP:rs1048945Ensembl. | 1 | |
Natural variantiVAR_014823 | 64 | I → V1 PublicationCorresponds to variant dbSNP:rs2307486EnsemblClinVar. | 1 | |
Natural variantiVAR_019790 | 148 | D → E2 PublicationsCorresponds to variant dbSNP:rs1130409Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi 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 |
Genome annotation databases
Ensembli | ENST00000216714; ENSP00000216714; ENSG00000100823 ENST00000398030; ENSP00000381111; ENSG00000100823 ENST00000555414; ENSP00000451979; ENSG00000100823 |
GeneIDi | 328 |
KEGGi | hsa:328 |
MANE-Selecti | ENST00000216714.8; ENSP00000216714.3; NM_001641.4; NP_001632.2 |
UCSCi | uc058yte.1, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
NIEHS-SNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi 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 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB 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 | [»] | |
4QH9 | X-ray | 2.18 | A | 38-318 | [»] | |
4QHD | X-ray | 1.65 | A | 38-318 | [»] | |
4QHE | X-ray | 1.40 | A | 38-318 | [»] | |
5CFG | X-ray | 1.80 | A | 44-318 | [»] | |
5DFF | X-ray | 1.57 | A/B | 43-318 | [»] | |
5DFH | X-ray | 1.95 | A/B | 43-318 | [»] | |
5DFI | X-ray | 1.63 | A/B | 43-318 | [»] | |
5DFJ | X-ray | 1.85 | A/B | 43-318 | [»] | |
5DG0 | X-ray | 1.80 | A/B | 43-318 | [»] | |
5WN0 | X-ray | 2.60 | A/B | 43-318 | [»] | |
5WN1 | X-ray | 2.30 | A/B | 43-318 | [»] | |
5WN2 | X-ray | 2.29 | A/B | 43-318 | [»] | |
5WN3 | X-ray | 2.00 | A/B | 43-318 | [»] | |
5WN4 | X-ray | 2.10 | A/B | 43-318 | [»] | |
5WN5 | X-ray | 2.20 | A/B | 43-318 | [»] | |
6BOQ | X-ray | 1.96 | A/B | 1-318 | [»] | |
6BOR | X-ray | 1.84 | A/B | 1-318 | [»] | |
6BOS | X-ray | 2.30 | A/B | 1-318 | [»] | |
6BOT | X-ray | 2.30 | A/B | 1-318 | [»] | |
6BOU | X-ray | 2.54 | A/B | 1-318 | [»] | |
6BOV | X-ray | 1.98 | A/B | 1-318 | [»] | |
6BOW | X-ray | 1.59 | A/B | 1-318 | [»] | |
6MK3 | X-ray | 1.48 | A | 40-318 | [»] | |
6MKK | X-ray | 1.44 | A | 40-318 | [»] | |
6MKM | X-ray | 1.67 | A | 40-318 | [»] | |
6MKO | X-ray | 2.09 | A | 40-318 | [»] | |
6P93 | X-ray | 2.10 | A/B | 43-318 | [»] | |
6P94 | X-ray | 2.09 | A/B | 43-318 | [»] | |
6W0Q | X-ray | 1.89 | A/B | 43-318 | [»] | |
6W2P | X-ray | 1.94 | A/B | 43-318 | [»] | |
6W3L | X-ray | 2.59 | A/B | 43-318 | [»] | |
6W3N | X-ray | 2.69 | A/B | 43-318 | [»] | |
6W3Q | X-ray | 2.49 | A/B | 43-318 | [»] | |
6W3U | X-ray | 2.40 | A/B | 43-318 | [»] | |
6W43 | X-ray | 1.99 | A/B | 43-318 | [»] | |
6W4I | X-ray | 2.20 | A/B | 43-318 | [»] | |
6W4T | X-ray | 2.77 | A/B | 43-318 | [»] | |
7LPG | X-ray | 2.08 | B/D | 43-318 | [»] | |
7LPH | X-ray | 1.99 | B/D | 43-318 | [»] | |
7LPI | X-ray | 2.05 | B/D | 43-318 | [»] | |
7LPJ | X-ray | 2.56 | B/D | 43-318 | [»] | |
BMRBi | P27695 | |||||
SMRi | P27695 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 106825, 1237 interactors |
CORUMi | P27695 |
DIPi | DIP-6130N |
IntActi | P27695, 54 interactors |
MINTi | P27695 |
STRINGi | 9606.ENSP00000216714 |
Chemistry databases
BindingDBi | P27695 |
ChEMBLi | CHEMBL5619 |
DrugBanki | DB04967, Lucanthone |
DrugCentrali | P27695 |
PTM databases
GlyGeni | P27695, 1 site, 2 O-linked glycans (1 site) |
iPTMneti | P27695 |
MetOSitei | P27695 |
PhosphoSitePlusi | P27695 |
SwissPalmi | P27695 |
Genetic variation databases
BioMutai | APEX1 |
DMDMi | 113984 |
Proteomic databases
CPTACi | CPTAC-23 CPTAC-24 |
EPDi | P27695 |
jPOSTi | P27695 |
MassIVEi | P27695 |
PaxDbi | P27695 |
PeptideAtlasi | P27695 |
PRIDEi | P27695 |
ProteomicsDBi | 54406 |
TopDownProteomicsi | P27695 |
Protocols and materials databases
Antibodypediai | 62, 925 antibodies from 46 providers |
CPTCi | P27695, 1 antibody |
DNASUi | 328 |
Genome annotation databases
Ensembli | ENST00000216714; ENSP00000216714; ENSG00000100823 ENST00000398030; ENSP00000381111; ENSG00000100823 ENST00000555414; ENSP00000451979; ENSG00000100823 |
GeneIDi | 328 |
KEGGi | hsa:328 |
MANE-Selecti | ENST00000216714.8; ENSP00000216714.3; NM_001641.4; NP_001632.2 |
UCSCi | uc058yte.1, human |
Organism-specific databases
CTDi | 328 |
DisGeNETi | 328 |
GeneCardsi | APEX1 |
HGNCi | HGNC:587, APEX1 |
HPAi | ENSG00000100823, Low tissue specificity |
MIMi | 107748, gene |
neXtProti | NX_P27695 |
OpenTargetsi | ENSG00000100823 |
PharmGKBi | PA201059 |
VEuPathDBi | HostDB:ENSG00000100823 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1294, Eukaryota |
GeneTreei | ENSGT00530000063540 |
HOGENOMi | CLU_027539_1_3_1 |
InParanoidi | P27695 |
OMAi | WRIDHIY |
OrthoDBi | 1105625at2759 |
PhylomeDBi | P27695 |
TreeFami | TF315048 |
Enzyme and pathway databases
BRENDAi | 4.2.99.18, 2681 |
PathwayCommonsi | P27695 |
Reactomei | R-HSA-110357, Displacement of DNA glycosylase by APEX1 R-HSA-110362, POLB-Dependent Long Patch Base Excision Repair R-HSA-110373, Resolution of AP sites via the multiple-nucleotide patch replacement pathway R-HSA-5651801, PCNA-Dependent Long Patch Base Excision Repair R-HSA-73930, Abasic sugar-phosphate removal via the single-nucleotide replacement pathway R-HSA-73933, Resolution of Abasic Sites (AP sites) |
SignaLinki | P27695 |
SIGNORi | P27695 |
Miscellaneous databases
BioGRID-ORCSi | 328, 16 hits in 1051 CRISPR screens |
ChiTaRSi | APEX1, human |
EvolutionaryTracei | P27695 |
GeneWikii | APEX1 |
GenomeRNAii | 328 |
Pharosi | P27695, Tchem |
PROi | PR:P27695 |
RNActi | P27695, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000100823, Expressed in subventricular zone (inner) (primate) and 242 other tissues |
ExpressionAtlasi | P27695, baseline and differential |
Genevisiblei | P27695, HS |
Family and domain databases
DisProti | DP00007 |
Gene3Di | 3.60.10.10, 1 hit |
InterProi | View protein in InterPro IPR004808, AP_endonuc_1 IPR020847, AP_endonuclease_F1_BS IPR020848, AP_endonuclease_F1_CS IPR036691, Endo/exonu/phosph_ase_sf IPR005135, Endo/exonuclease/phosphatase |
PANTHERi | PTHR22748, PTHR22748, 1 hit |
Pfami | View protein in Pfam PF03372, Exo_endo_phos, 1 hit |
SUPFAMi | SSF56219, SSF56219, 1 hit |
TIGRFAMsi | TIGR00633, xth, 1 hit |
PROSITEi | View protein in PROSITE 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 |
MobiDBi | Search... |
Entry informationi
Entry namei | APEX1_HUMAN | |
Accessioni | P27695Primary (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: | February 23, 2022 | |
This is version 250 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 14
Human chromosome 14: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families