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APEX1 Gene

protein-coding   GIFtS: 70
GCID: GC14P020924

APEX Nuclease (Multifunctional DNA Repair Enzyme) 1

(Previous name: APEX nuclease (multifunctional DNA repair enzyme))
(Previous symbol: APEX)
  See APEX1-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
APEX Nuclease (Multifunctional DNA Repair Enzyme) 11 2     AP Endonuclease Class I2
APEX1 2 3 5     AP Lyase2
APE2 3 5     Apurinic/Apyrimidinic (Abasic) Endonuclease2
Apurinic-Apyrimidinic Endonuclease 12 3     Deoxyribonuclease (Apurinic Or Apyrimidinic)2
Redox Factor-12 3     DNA-(Apurinic Or Apyrimidinic Site) Lyase2
APE12 3     Protein REF-12
APEN2 3     APE-13
APX2 3     EC 3.1.-.-3
HAP12 3     REF-13
REF12 3     AP Endonuclease 13
EC 4.2.99.183 8     APEX Nuclease3
APEX Nuclease (Multifunctional DNA Repair Enzyme)1     

External Ids:    HGNC: 5871   Entrez Gene: 3282   Ensembl: ENSG000001008237   OMIM: 1077485   UniProtKB: P276953   

Export aliases for APEX1 gene to outside databases

Previous GC identifers: GC14P018294 GC14P014710 GC14P018913 GC14P019993 GC14P001044


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for APEX1 Gene:
Apurinic/apyrimidinic (AP) sites occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging
agents or by DNA glycosylases that remove specific abnormal bases. AP sites are pre-mutagenic lesions that can
prevent normal DNA replication so the cell contains systems to identify and repair such sites. Class II AP
endonucleases cleave the phosphodiester backbone 5' to the AP site. This gene encodes the major AP endonuclease
in human cells. Splice variants have been found for this gene; all encode the same protein. (provided by RefSeq,
Jul 2008)

GeneCards Summary for APEX1 Gene:
APEX1 (APEX nuclease (multifunctional DNA repair enzyme) 1) is a protein-coding gene. Diseases associated with APEX1 include attenuated familial adenomatous polyposis, and respiratory failure. GO annotations related to this gene include RNA binding and transcription corepressor activity. An important paralog of this gene is APEX2.

UniProtKB/Swiss-Prot: APEX1_HUMAN, P27695
Function: 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

Gene Wiki entry for APEX1 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000014.8  NT_026437.13  NC_018925.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the APEX1 gene promoter:
         GR   AP-1   STAT3   GR-alpha   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): APEX1 promoter sequence
   Search Chromatin IP Primers for APEX1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat APEX1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 14q11.2   Ensembl cytogenetic band:  14q11.2   HGNC cytogenetic band: 14q11.2

APEX1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
APEX1 gene location

GeneLoc information about chromosome 14         GeneLoc Exon Structure

GeneLoc location for GC14P020924:  view genomic region     (about GC identifiers)

Start:
20,923,290 bp from pter      End:
20,925,927 bp from pter
Size:
2,638 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: APEX1_HUMAN, P27695 (See protein sequence)
Recommended Name: DNA-(apurinic or apyrimidinic site) lyase  
Size: 318 amino acids; 35555 Da
Cofactor: Magnesium. Can also utilize manganese. Probably binds two magnesium or manganese ions per subunit
Subunit: Monomer. Homodimer; disulfide-linked. Component of the SET complex, composed at least of APEX1, GZMA,
SET, ANP32A, HMGB2 and NME1. 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 (By similarity)
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
Selected PDB 3D structures from and Proteopedia for APEX1 (see all 13):
1BIX (3D)        1CQG (3D)        1CQH (3D)        1DE8 (3D)        1DE9 (3D)        1DEW (3D)    
Secondary accessions: Q969L5 Q99775

Explore the universe of human proteins at neXtProt for APEX1: NX_P27695

Explore proteomics data for APEX1 at MOPED

Post-translational modifications: 

  • 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 death1
  • 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 SIRT11
  • 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 stress1
  • 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
  • Ubiquitinated by MDM2; leading to translocation to the cytoplasm and proteasomal degradation1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for APEX1 (P27695) (see all 6)
     NVGWRLDY  AYTFWTYM  LKICSWNV  DSFRHLYPNT 


    See APEX1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (4 alternative transcripts): 
    NP_001231178.1  NP_001632.2  NP_542379.1  NP_542380.1  

    ENSEMBL proteins: 
     ENSP00000451979   ENSP00000216714   ENSP00000451327   ENSP00000452137   ENSP00000381111  
     ENSP00000450604   ENSP00000452304   ENSP00000452460   ENSP00000451491   ENSP00000451170  
     ENSP00000452212   ENSP00000451060   ENSP00000452418   ENSP00000416414  
    Reactome Protein details: P27695

    APEX1 Human Recombinant Protein Products:

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    Novus Biologicals APEX1 Lysates
    Sino Biological Recombinant Protein for APEX1
    Browse Sino Biological Cell Lysates
    ProSpec Recombinant Protein for APEX1
    Cloud-Clone Corp. Proteins for APEX1

     
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    antibodies-online proteins for APEX1 (21 products) 

     
    antibodies-online peptides for APEX1

    APEX1 Antibody Products:

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    antibodies-online antibodies for APEX1 (127 products) 

    APEX1 Assay Products:

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    4 InterPro protein domains:
     IPR020848 AP_endonuclease_F1_CS
     IPR020847 AP_endonuclease_F1_BS
     IPR004808 AP_endonuc_1
     IPR005135 Endo/exonuclease/phosphatase

    Graphical View of Domain Structure for InterPro Entry P27695

    ProtoNet protein and cluster: P27695

    1 Blocks protein domain: IPB000097 AP endonuclease

    UniProtKB/Swiss-Prot: APEX1_HUMAN, P27695
    Domain: 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
    Similarity: Belongs to the DNA repair enzymes AP/ExoA family


    Find genes that share domains with APEX1           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: APEX1_HUMAN, P27695
    Function: 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
    Catalytic activity: 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
    Enzyme regulation: NPM1 stimulates endodeoxyribonuclease activity on double-stranded DNA with AP sites, but
    inhibits endoribonuclease activity on single-stranded RNA containing AP sites
    Induction: Up-regulated in presence of reactive oxygen species (ROS), like bleomycin, H(2)O(2) and phenazine
    methosulfate

         Enzyme Numbers (IUBMB): EC 4.2.99.181 2 EC 3.1.-.-1

         Gene Ontology (GO): Selected molecular function terms (see all 23):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003677DNA binding IDA11286553
    GO:0003684damaged DNA binding IDA12524539
    GO:0003713transcription coactivator activity IDA9119221
    GO:0003714transcription corepressor activity TAS7961715
    GO:0003723RNA binding ----
         
    Find genes that share ontologies with APEX1           About GenesLikeMe


    Phenotypes:
         13 MGI mutant phenotypes (inferred from 4 alleles(MGI details for Apex1):
     cardiovascular system  cellular  embryogenesis  endocrine/exocrine gland  growth/size/body 
     homeostasis/metabolism  immune system  liver/biliary system  mortality/aging  muscle 
     normal  reproductive system  tumorigenesis 

    Find genes that share phenotypes with APEX1           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for APEX1: Apex1tm1Cur Apex1tm1Djc

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for APEX1
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for APEX1

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for APEX1
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for APEX1

    miRNA
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    miRTarBase miRNAs that target APEX1:
    hsa-mir-100-5p (MIRT048405), hsa-mir-17-5p (MIRT050830), hsa-mir-935 (MIRT036701), hsa-mir-99a-5p (MIRT048610), hsa-mir-185-5p (MIRT045386)

    Block miRNA regulation of human, mouse, rat APEX1 using miScript Target Protectors
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    SwitchGear 3'UTR luciferase reporter plasmidAPEX1 3' UTR sequence
    Inhib. RNA
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    APEX1_HUMAN, P27695: Nucleus. 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
    APEX1_HUMAN, P27695: 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
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    endoplasmic reticulum5
    mitochondrion5
    nucleus5
    cytoskeleton4
    cytosol2

    Gene Ontology (GO): Selected cellular component terms (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005622intracellular ----
    GO:0005634nucleus IDA--
    GO:0005654nucleoplasm TAS--
    GO:0005667transcription factor complex IEA--
    GO:0005730nucleolus IDA17148573

    Find genes that share ontologies with APEX1           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for APEX1 About   (see all 14)  
    See pathways by source

    SuperPathContained pathways About
    1Resolution of Abasic Sites (AP sites)
    Resolution of Abasic Sites (AP sites)0.89
    Base Excision Repair0.00
    Resolution of AP sites via the multiple-nucleotide patch replacement pathway0.89
    Displacement of DNA glycosylase by APE10.00
    Base excision repair0.53
    Resolution of AP sites via the single-nucleotide replacement pathway0.00
    Base-free sugar-phosphate removal via the single-nucleotide replacement pathway0.00
    Removal of DNA patch containing abasic residue0.00
    2Cell Cycle / Checkpoint Control
    Cell Cycle / Checkpoint Control0.32
    DNA Damage0.32
    3DNA Repair
    DNA Repair0.45
    4Activation of DNA fragmentation factor
    Granzyme-A Pathway0.32
    5Chks in Checkpoint Regulation
    DNA Repair Mechanisms0.32


    Find genes that share SuperPaths with APEX1           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    4 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for APEX1
        Granzyme-A Pathway
    DNA Repair Mechanisms
    HIF1Alpha Pathway
    Granzyme Pathway

    4 Cell Signaling Technology (CST) Pathways for APEX1
        Cell Cycle / Checkpoint Control
    Neuroscience
    Lymphocyte Signaling
    DNA Damage

    1 GeneGo (Thomson Reuters) Pathway for APEX1
        Transcription P53 signaling pathway

    3 BioSystems Pathways for APEX1
        Spinal Cord Injury
    TSH signaling pathway
    HIF-2-alpha transcription factor network


    4 Reactome Pathways for APEX1
        Removal of DNA patch containing abasic residue
    Displacement of DNA glycosylase by APE1
    Resolution of AP sites via the multiple-nucleotide patch replacement pathway
    Base-free sugar-phosphate removal via the single-nucleotide replacement pathway

    1 PharmGKB Pathway for APEX1
        Busulfan Pathway, Pharmacodynamics

    1 Kegg Pathway  (Kegg details for APEX1):
        Base excision repair

        Pathway & Disease-focused RT2 Profiler PCR Arrays including APEX1 (see all 7): 
              HIV Host Response in human mouse rat
              DNA Damage Signaling Pathway in human mouse rat
              p53 Signaling Pathway in human mouse rat
              Hypoxia Signaling Pathway in human mouse rat
              DNA Repair in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for APEX1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for APEX1 (P276951, 2, 3 ENSP000002167144) via UniProtKB, MINT, STRING, and/or I2D (see all 132)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ENSG00000232804P081072, 3, ENSP000003930874MINT-16427 MINT-16428 MINT-8076071 I2D: score=3 STRING: ENSP00000393087
    ENSG00000212866P081072, 3MINT-16427 MINT-16428 MINT-8076071 I2D: score=3 
    ENSG00000215328P081072, 3MINT-16427 MINT-16428 MINT-8076071 I2D: score=3 
    ENSG00000224501P081072, 3MINT-16427 MINT-16428 MINT-8076071 I2D: score=3 
    ENSG00000231555P081072, 3MINT-16427 MINT-16428 MINT-8076071 I2D: score=3 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 22):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000737DNA catabolic process, endonucleolytic TAS1722334
    GO:0006281DNA repair TAS--
    GO:0006284base-excision repair TAS--
    GO:0006310DNA recombination IEA--
    GO:0006351transcription, DNA-templated IEA--

    Find genes that share ontologies with APEX1           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
    About This Section

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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for APEX1

    1 HMDB Compound for APEX1    About this table
    CompoundSynonyms CAS #PubMed Ids
    MagnesiumMagnesium (see all 2)7439-95-4--

    1 DrugBank Compound for APEX1    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Lucanthone1-((2-(Diethylamino)ethyl)amino)-4-methylthioxanthen-9-one (see all 7)479-50-5targetinhibitor15330152

    Selected Novoseek inferred chemical compound relationships for APEX1 gene (see all 95)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    8-oxoguanine 77.5 10 11937636 (1), 16051529 (1), 18685817 (1), 15541770 (1) (see all 9)
    methylmethanesulfonate 72.7 9 15210853 (1), 15330152 (1), 1627644 (1), 18776186 (1) (see all 7)
    deoxyribose-5-phosphate 67.6 1 9207062 (1)
    troxacitabine 67.6 1 19470598 (1)
    3,n(4)-ethenocytosine 67.2 2 11506820 (1), 12161446 (1)
    phosphoglycolate 66.7 2 7516064 (1), 9171104 (1)
    fibrinolysin 65.2 8 11937475 (5), 9239167 (2), 1973756 (1)
    lucanthone 63.7 9 15330152 (6), 12449731 (1)
    phosphodiester 62.8 18 20073480 (1), 11356334 (1), 11554453 (1), 9870152 (1) (see all 13)
    2-deoxyribonolactone 62 3 16623699 (1), 16199212 (1)



    Find genes that share compounds with APEX1           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
    About This Section

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    REFSEQ mRNAs for APEX1 gene (4 alternative transcripts): 
    NM_001244249.1  NM_001641.3  NM_080648.2  NM_080649.2  

    Unigene Cluster for APEX1:

    APEX nuclease (multifunctional DNA repair enzyme) 1
    Hs.73722  [show with all ESTs]
    Unigene Representative Sequence: NM_001641
    Selected Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 20):
    ENST00000555414(uc001vxh.3 uc001vxi.3) ENST00000216714(uc001vxg.3 uc021rnr.1)
    ENST00000553681 ENST00000554813 ENST00000556296 ENST00000557344 ENST00000555306
    ENST00000553555 ENST00000398030 ENST00000554325 ENST00000557181 ENST00000555839
    ENST00000557159 ENST00000553368 ENST00000556054 ENST00000557054 ENST00000557592
    ENST00000557365
    miRNA
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    Flow Cytometry
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    eBioscience FlowRNA Probe Sets ( VA1-12294 VA1-12831) for APEX1 

    Additional mRNA sequence: 

    AK098588.1 AK291100.1 AK311548.1 BC002338.2 BC004979.1 BC008145.1 BC019291.1 BC095428.1 
    BT007236.1 BT020133.1 BX161454.1 D90373.1 M80261.1 M81955.1 S43127.1 U79268.1 
    X59764.1 

    Selected DOTS entries (see all 40):

    DT.450716  DT.91865427  DT.97860983  DT.95340211  DT.97860985  DT.100045339  DT.100840911  DT.100892357 
    DT.120732604  DT.100892368  DT.117122  DT.100892372  DT.92466528  DT.102837774  DT.100892382  DT.100892402 
    DT.120732702  DT.100892406  DT.100763085  DT.95310093  DT.120733139  DT.100807403  DT.100808976  DT.100892365 

    Selected AceView cDNA sequences (see all 942):

    CB123270 BX438832 CR607088 CR611978 BQ422388 CR613058 BU169571 CB114533 
    BF808175 CR611116 CB132219 CR594913 BM972357 BX457931 CR593576 CR605968 
    CR595578 CR597601 F10089 CB127562 BQ182631 BM739177 BP870943 CB127545 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for APEX1 (see all 19)    About this scheme

    ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b · 2c · 2d · 2e · 2f · 2g · 2h ^ 3a · 3b · 3c · 3d ^ 4 ^ 5 ^ 6 ^ 7a · 7b · 7c · 7d ^ 8 ^ 9a · 9b ·
    SP1:                                                        -     -     -     -     -           -     -                                                         
    SP2:                          -     -     -     -     -     -     -     -     -     -           -     -                                                         
    SP3:                                                              -     -     -     -           -     -                                                         
    SP4:                                                              -     -     -     -           -     -                                         -               
    SP5:                                                  -     -     -     -     -     -           -     -                                                         

    ExUns: 9c · 9d · 9e · 9f · 9g · 9h
    SP1:                                    
    SP2:                                    
    SP3:                                    
    SP4:                                    
    SP5:                                    


    ECgene alternative splicing isoforms for APEX1

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    APEX1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AAAATAAAGA
    APEX1 Expression
    About this image


    APEX1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 22) fully expand
     
     Brain (Nervous System)    fully expand to see all 4 entries
             Cerebral Cortex
     
     Gut Tube (Gastrointestinal Tract)    fully expand to see all 3 entries
             Hindgut
     
     Ovary (Reproductive System)    fully expand to see all 2 entries
             Ovarian Mesenchymal Stroma Cells Ovary Interstitium
             Oviduct
     
     Kidney (Urinary System)
             Metanephros
     
     Thymus (Hematopoietic System)
             Thymus
    APEX1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    APEX1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.73722
        Pathway & Disease-focused RT2 Profiler PCR Arrays including APEX1 (see all 7): 
              HIV Host Response in human mouse rat
              DNA Damage Signaling Pathway in human mouse rat
              p53 Signaling Pathway in human mouse rat
              Hypoxia Signaling Pathway in human mouse rat
              DNA Repair in human mouse rat

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    In Situ
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for APEX1

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of eukaryotes.

    Orthologs for APEX1 gene from Selected species (see all 20)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Apex11 , 5 apurinic/apyrimidinic endonuclease 11, 5 86.75(n)1
    94.64(a)1
      14 (26.30 cM)5
    117921  NM_009687.21  NP_033817.11 
     509249685 
    chicken
    (Gallus gallus)
    Aves APEX11 APEX nuclease (multifunctional DNA repair enzyme) 1 less 60.56(n)
    63.33(a)
      100431102  NM_001184759.1  NP_001171688.1 
    lizard
    (Anolis carolinensis)
    Reptilia APEX16
    APEX nuclease (multifunctional DNA repair enzyme) ...
    69(a)
    1 ↔ 1
    GL343220.1(1204334-1212440)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.247952 Xenopus laevis transcribed sequence with weak similarity to protein prf2019234A (H.sapiens) 2019234A APEX nuclease [Homo sapiens] less 72.36(n)    CF548074.1 
    zebrafish
    (Danio rerio)
    Actinopterygii hmzehn15322 Danio rerio cDNA clone MGC66204 IMAGE5914323, complete cds less 72.86(n)    BC055545.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Rrp16
    Recombination repair protein 1
    22(a)
    1 ↔ 1
    2L(2969773-2972676)
    worm
    (Caenorhabditis elegans)
    Secernentea exo-36
    Protein EXO-3, isoform a
    41(a)
    1 ↔ 1
    I(11907555-11909280) WBGene00001372
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes APN26
    Class II abasic (AP) endonuclease involved in repa...
    13(a)
    1 → many
    II(184353-185915) YBL019W
    thale cress
    (Arabidopsis thaliana)
    eudicotyledons ARP1 ARP 51.76(n)
    49.8(a)
      818744  NM_129709.4  NP_181677.1 
    rice
    (Oryza sativa)
    Liliopsida Os01g08010001 Os01g0801000 50.55(n)
    46.55(a)
      4327960  NM_001051072.1  NP_001044537.1 


    ENSEMBL Gene Tree for APEX1 (if available)
    TreeFam Gene Tree for APEX1 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for APEX1 gene
    APEX22  

    Find genes that share paralogs with APEX1           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
    About This Section

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    Selected SNPs for APEX1 (see all 164)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 14 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1829394541,2
    C--1042925(+) CAGCTC/TAATCA 4 -- us2k10--------
    rs1874786081,2
    --1920400(+) AAGCAC/TTGAGT 4 -- us2k10--------
    rs1390125591,2
    --1920554(+) CTATGC/TATGCA 4 -- us2k10--------
    rs114759211,2
    C--1920634(+) TTGTAC/-TTTTT 4 -- us2k1 trp31Minor allele frequency- -:0.50CSA 2
    rs777949161,2
    C,F--1920634(+) TTGTAC/TTTTTT 4 -- us2k12Minor allele frequency- T:0.50WA NA 4
    rs1920906801,2
    C--1920859(+) AACCCC/TGACCT 4 -- us2k10--------
    rs1123560311,2
    C--1920925(+) CCACGC/TCCAGC 4 -- us2k11Minor allele frequency- T:0.50CSA 2
    rs761414901,2
    --1920930(+) CCCAGA/CCGTGT 4 -- us2k10--------
    rs1161461171,2
    C,F--1920968(+) CTAATG/AATACA 4 -- us2k12Minor allele frequency- A:0.09WA EA 238
    rs1841924531,2
    --1921012(+) CCCGAC/GCGGTG 4 -- us2k10--------

    HapMap Linkage Disequilibrium report for APEX1 (20923290 - 20925927 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 1 variation for APEX1:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv23438CNV Gain+Loss19812545

    Human Gene Mutation Database (HGMD): APEX1
    Site Specific Mutation Identification with PCR Assays
    Search QIAGEN SeqTarget long-range PCR primers for resequencing APEX1
    DNA2.0 Custom Variant and Variant Library Synthesis for APEX1

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 107748    OMIM disorders: --

    6 diseases for APEX1:    
    About MalaCards
    attenuated familial adenomatous polyposis    respiratory failure    cystic fibrosis    amyotrophic lateral sclerosis
    lung cancer    breast cancer


    Find genes that share disorders with APEX1           About GenesLikeMe

    Selected Novoseek inferred disease relationships for APEX1 gene (see all 55)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    cystic fibrosis 65.1 56 10796748 (4), 20298317 (3), 7800431 (2), 12917899 (2) (see all 39)
    atelectasis 39.6 7 20298317 (2), 19489944 (2), 11716180 (1)
    lung diseases 34.3 8 12023366 (2), 12917899 (1), 8680379 (1), 16236891 (1) (see all 7)
    cancer 29.3 41 18627350 (4), 20087352 (3), 19072053 (2), 11316543 (2) (see all 17)
    tumors 12.9 58 18809583 (3), 18535621 (3), 16823850 (2), 11420300 (2) (see all 31)
    xeroderma pigmentosum 12.9 2 7775413 (1), 18946634 (1)
    amyotrophic lateral sclerosis 11.8 3 9507962 (1), 18482781 (1)
    diphtheria 9.11 4 2109323 (1), 9783263 (1), 15680246 (1), 2318891 (1)
    bronchiolitis 7.89 3 17356094 (2), 11716180 (1)
    cancer lung 7.51 13 19124501 (5), 19528510 (4), 15333465 (2), 18809583 (1) (see all 5)

    Genetic Association Database (GAD): APEX1
    Human Genome Epidemiology (HuGE) Navigator: APEX1 (127 documents)

    Export disorders for APEX1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for APEX1 gene, integrated from 10 sources (see all 746):
    (articles sorted by number of sources associating them with APEX1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III. (PubMed id 1627644)1, 2, 9 Seki S.... Tsutsui K. (Biochim. Biophys. Acta 1992)
    2. Characterization of abasic endonuclease activity of human Ape1 on alternative substrates, as well as effects of ATP and sequence context on AP site incision. (PubMed id 18439621)1, 2, 9 Berquist B.R.... Wilson D.M. III (J. Mol. Biol. 2008)
    3. Genetic variants of the ADPRT, XRCC1 and APE1 genes and risk of cutaneous melanoma. (PubMed id 16621887)1, 4, 9 Li C....Wei Q. (Carcinogenesis 2006)
    4. Human AP-endonuclease 1 and hnRNP-L interact with a nCaRE-like repressor element in the AP-endonuclease 1 promoter. (PubMed id 11809897)1, 2, 9 Kuninger D.T.... Mitra S. (Nucleic Acids Res. 2002)
    5. Identification of apurinic/apyrimidinic endonuclease 1 (APE1) as the endoribonuclease that cleaves c-myc mRNA. (PubMed id 19401441)1, 2, 9 Barnes T....Lee C.H. (Nucleic Acids Res. 2009)
    6. A polymorphism in the APE1 gene promoter is associated with lung cancer risk. (PubMed id 19124501)1, 4, 9 Lo Y.L....Hsiung C.A. (amp 2009)
    7. Apurinic/apyrimidinic endonuclease (APE1) gene polymorphisms and lung cancer risk in relation to tobacco smoking. (PubMed id 19528510)1, 4, 9 AgaAshan B....Isbir T. (Anticancer Res. 2009)
    8. DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination. (PubMed id 10667800)1, 2, 9 Mol C.D.... Tainer J.A. (Nature 2000)
    9. Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation. (PubMed id 11118054)1, 2, 9 Wei S.J.... Gius D. (Cancer Res. 2000)
    10. AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1. (PubMed id 9108029)1, 2, 9 Hirota K.... Yodoi J. (Proc. Natl. Acad. Sci. U.S.A. 1997)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section

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    Entrez Gene: 328 HGNC: 587 AceView: APEX1 Ensembl:ENSG00000100823 euGenes: HUgn328
    ECgene: APEX1 Kegg: 328 H-InvDB: APEX1

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for APEX1 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for APEX1 Genetics and Cytogenetics in Oncology and Haematology
    NIEHS-SNPshttp://egp.gs.washington.edu/data/apex/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for APEX1 gene:
    Search GeneIP for patents involving APEX1

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
    Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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     Search www.enzolifesciences.com for proteins, assays, substrates, inhibitors & antibodies

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     inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for APEX1
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     antibodies-online antibodies for APEX1 (127 products)
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