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Protein

DNA-(apurinic or apyrimidinic site) lyase

Gene

APEX1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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.PROSITE-ProRule annotation5 Publications

Cofactori

Mg2+4 Publications, Mn2+4 PublicationsNote: 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
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

GO - Molecular functioni

  • 3'-5' exonuclease activity Source: UniProtKB
  • chromatin DNA binding Source: UniProtKB
  • damaged DNA binding Source: UniProtKB
  • DNA-(apurinic or apyrimidinic site) lyase 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
  • oxidoreductase activity Source: UniProtKB
  • phosphodiesterase I activity Source: UniProtKB
  • phosphoric diester hydrolase activity Source: UniProtKB
  • poly(A) 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

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.
ReactomeiR-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).

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
Proteomesi
  • UP000005640 Componenti: 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
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

  • centrosome Source: HPA
  • cytoplasm Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • nuclear chromosome, telomeric region Source: BHF-UCL
  • nuclear speck Source: UniProtKB
  • nucleolus Source: UniProtKB
  • nucleoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • ribosome Source: UniProtKB
  • 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.

Chemistry

ChEMBLiCHEMBL5619.
DrugBankiDB04967. Lucanthone.

Polymorphism and mutation databases

BioMutaiAPEX1.
DMDMi113984.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved2 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
Modified residuei54 – 541PhosphoserineCombined sources
Disulfide bondi65 ↔ 93AlternateCurated
Modified residuei65 – 651S-nitrosocysteine; alternate1 Publication
Modified residuei93 – 931S-nitrosocysteine; alternate1 Publication
Modified residuei197 – 1971N6-acetyllysineCombined sources
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 SIRT1.2 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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei31 – 322Cleavage; by granzyme A

Keywords - PTMi

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

Proteomic databases

EPDiP27695.
PaxDbiP27695.
PeptideAtlasiP27695.
PRIDEiP27695.
TopDownProteomicsiP27695.

PTM databases

iPTMnetiP27695.
PhosphoSiteiP27695.
SwissPalmiP27695.

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

BgeeiENSG00000100823.
CleanExiHS_APEX1.
HS_HAP1.
ExpressionAtlasiP27695. baseline and differential.
GenevisibleiP27695. HS.

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei309 – 3091Interaction with DNA substrate

Binary interactionsi

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

Protein-protein interaction databases

BioGridi106825. 84 interactions.
DIPiDIP-6130N.
IntActiP27695. 37 interactions.
MINTiMINT-119189.
STRINGi9606.ENSP00000216714.

Chemistry

BindingDBiP27695.

Structurei

Secondary structure

1
318
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi62 – 687Combined sources
Helixi72 – 776Combined sources
Helixi80 – 878Combined sources
Beta strandi90 – 956Combined sources
Helixi101 – 1033Combined sources
Helixi106 – 1105Combined sources
Helixi112 – 1143Combined sources
Beta strandi116 – 1205Combined sources
Beta strandi123 – 1253Combined sources
Beta strandi127 – 1293Combined sources
Beta strandi131 – 1377Combined sources
Beta strandi140 – 1456Combined sources
Helixi149 – 1513Combined sources
Beta strandi152 – 1543Combined sources
Beta strandi157 – 1615Combined sources
Beta strandi166 – 1716Combined sources
Helixi177 – 1793Combined sources
Helixi182 – 20019Combined sources
Beta strandi205 – 2106Combined sources
Helixi217 – 2193Combined sources
Turni224 – 2285Combined sources
Turni230 – 2323Combined sources
Helixi234 – 24613Combined sources
Beta strandi249 – 2513Combined sources
Helixi252 – 2565Combined sources
Beta strandi257 – 2593Combined sources
Helixi270 – 2723Combined sources
Helixi273 – 2764Combined sources
Beta strandi283 – 2875Combined sources
Helixi289 – 2946Combined sources
Beta strandi295 – 3006Combined sources
Beta strandi306 – 3094Combined sources
Beta strandi312 – 3165Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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[»]
4QH9X-ray2.18A38-318[»]
4QHDX-ray1.65A38-318[»]
4QHEX-ray1.40A38-318[»]
5DFFX-ray1.57A/B43-318[»]
5DFHX-ray1.95A/B43-318[»]
5DFIX-ray1.63A/B43-318[»]
5DFJX-ray1.85A/B43-318[»]
5DG0X-ray1.80A/B43-318[»]
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
Regioni23 – 3311Necessary for interaction with NPM1 and for efficient rRNA bindingAdd
BLAST
Regioni289 – 31830Mitochondrial targeting sequence (MTS)Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi8 – 136Nuclear localization signal (NLS)
Motifi64 – 8017Nuclear export signal (NES)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

eggNOGiKOG1294. Eukaryota.
COG0708. LUCA.
GeneTreeiENSGT00530000063540.
HOGENOMiHOG000034586.
HOVERGENiHBG050531.
InParanoidiP27695.
KOiK10771.
OMAiYTPNSQQ.
OrthoDBiEOG091G0FDG.
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:
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.
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.
UniGeneiHs.73722.

Genome annotation databases

EnsembliENST00000216714; ENSP00000216714; ENSG00000100823.
ENST00000398030; ENSP00000381111; ENSG00000100823.
ENST00000555414; ENSP00000451979; ENSG00000100823.
GeneIDi328.
KEGGihsa:328.
UCSCiuc058yte.1. human.

Keywords - Coding sequence diversityi

Polymorphism

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.
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.
UniGeneiHs.73722.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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[»]
4QH9X-ray2.18A38-318[»]
4QHDX-ray1.65A38-318[»]
4QHEX-ray1.40A38-318[»]
5DFFX-ray1.57A/B43-318[»]
5DFHX-ray1.95A/B43-318[»]
5DFIX-ray1.63A/B43-318[»]
5DFJX-ray1.85A/B43-318[»]
5DG0X-ray1.80A/B43-318[»]
DisProtiDP00007.
ProteinModelPortaliP27695.
SMRiP27695. Positions 44-318.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106825. 84 interactions.
DIPiDIP-6130N.
IntActiP27695. 37 interactions.
MINTiMINT-119189.
STRINGi9606.ENSP00000216714.

Chemistry

BindingDBiP27695.
ChEMBLiCHEMBL5619.
DrugBankiDB04967. Lucanthone.

PTM databases

iPTMnetiP27695.
PhosphoSiteiP27695.
SwissPalmiP27695.

Polymorphism and mutation databases

BioMutaiAPEX1.
DMDMi113984.

Proteomic databases

EPDiP27695.
PaxDbiP27695.
PeptideAtlasiP27695.
PRIDEiP27695.
TopDownProteomicsiP27695.

Protocols and materials databases

DNASUi328.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000216714; ENSP00000216714; ENSG00000100823.
ENST00000398030; ENSP00000381111; ENSG00000100823.
ENST00000555414; ENSP00000451979; ENSG00000100823.
GeneIDi328.
KEGGihsa:328.
UCSCiuc058yte.1. human.

Organism-specific databases

CTDi328.
GeneCardsiAPEX1.
HGNCiHGNC:587. APEX1.
HPAiCAB004294.
CAB047307.
HPA000956.
HPA002564.
MIMi107748. gene.
neXtProtiNX_P27695.
PharmGKBiPA201059.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1294. Eukaryota.
COG0708. LUCA.
GeneTreeiENSGT00530000063540.
HOGENOMiHOG000034586.
HOVERGENiHBG050531.
InParanoidiP27695.
KOiK10771.
OMAiYTPNSQQ.
OrthoDBiEOG091G0FDG.
PhylomeDBiP27695.
TreeFamiTF315048.

Enzyme and pathway databases

BRENDAi4.2.99.18. 2681.
ReactomeiR-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).

Miscellaneous databases

ChiTaRSiAPEX1. human.
EvolutionaryTraceiP27695.
GeneWikiiAPEX1.
GenomeRNAii328.
PMAP-CutDBP27695.
PROiP27695.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100823.
CleanExiHS_APEX1.
HS_HAP1.
ExpressionAtlasiP27695. baseline and differential.
GenevisibleiP27695. HS.

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]
ProtoNetiSearch...

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: September 7, 2016
This is version 207 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.