======= APEX1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: APEX1
  * **<color #00a2e8>Official Name</color>**: apurinic/apyrimidinic endodeoxyribonuclease 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=328|328]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P27695|P27695]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=APEX1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20APEX1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/107748|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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. {ECO:0000269|PubMed:10023679, ECO:0000269|PubMed:11118054, ECO:0000269|PubMed:11452037, ECO:0000269|PubMed:11809897, ECO:0000269|PubMed:11832948, ECO:0000269|PubMed:12524539, ECO:0000269|PubMed:16617147, ECO:0000269|PubMed:1719477, ECO:0000269|PubMed:18179823, ECO:0000269|PubMed:18439621, ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:18809583, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:19401441, ECO:0000269|PubMed:19934257, ECO:0000269|PubMed:20699270, ECO:0000269|PubMed:21496894, ECO:0000269|PubMed:21762700, ECO:0000269|PubMed:8355688, ECO:0000269|PubMed:8621488, ECO:0000269|PubMed:8932375, ECO:0000269|PubMed:9108029, ECO:0000269|PubMed:9207062, ECO:0000269|PubMed:9560228, ECO:0000269|PubMed:9804799}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Exo endo phos|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|telomere maintenance via base-excision repair|
|double-stranded DNA exodeoxyribonuclease activity|
|site-specific endodeoxyribonuclease activity, specific for altered base|
|base-excision repair, base-free sugar-phosphate removal|
|double-stranded DNA 3-5 exodeoxyribonuclease activity|
|DNA dephosphorylation|
|uracil DNA N-glycosylase activity|
|phosphodiesterase I activity|
|double-stranded telomeric DNA binding|
|endodeoxyribonuclease activity|
|telomere maintenance in response to DNA damage|
|class I DNA-(apurinic or apyrimidinic site) endonuclease activity|
|DNA-(apurinic or apyrimidinic site) endonuclease activity|
|phosphoric diester hydrolase activity|
|RNA-DNA hybrid ribonuclease activity|
|3-5 exonuclease activity|
|DNA demethylation|
|negative regulation of smooth muscle cell migration|
|DNA dealkylation|
|NF-kappaB binding|
|positive regulation of G1/S transition of mitotic cell cycle|
|endonuclease activity|
|base-excision repair|
|ribosome|
|positive regulation of cell cycle G1/S phase transition|
|cellular response to cAMP|
|damaged DNA binding|
|regulation of smooth muscle cell migration|
|demethylation|
|DNA methylation or demethylation|
|cellular response to hydrogen peroxide|
|chromatin DNA binding|
|cell redox homeostasis|
|positive regulation of mitotic cell cycle phase transition|
|RNA phosphodiester bond hydrolysis, endonucleolytic|
|DNA modification|
|positive regulation of cell cycle phase transition|
|telomere maintenance|
|response to cAMP|
|telomere organization|
|nuclear chromosome, telomeric region|
|cellular response to antibiotic|
|oxidoreductase activity|
|response to hydrogen peroxide|
|cellular response to reactive oxygen species|
|response to organophosphorus|
|regulation of G1/S transition of mitotic cell cycle|
|positive regulation of mitotic cell cycle|
|response to purine-containing compound|
|RNA phosphodiester bond hydrolysis|
|regulation of cell cycle G1/S phase transition|
|regulation of mRNA stability|
|regulation of RNA stability|
|response to reactive oxygen species|
|regulation of mRNA catabolic process|
|transcription factor complex|
|cellular response to toxic substance|
|DNA recombination|
|cellular response to oxidative stress|
|transcription corepressor activity|
|negative regulation of cell migration|
|cellular response to peptide hormone stimulus|
|protein-containing complex binding|
|negative regulation of cell motility|
|aging|
|transcription coactivator activity|
|positive regulation of cell cycle process|
|nucleic acid phosphodiester bond hydrolysis|
|response to antibiotic|
|negative regulation of cellular component movement|
|dephosphorylation|
|negative regulation of locomotion|
|cellular response to peptide|
|regulation of mRNA metabolic process|
|anatomical structure homeostasis|
|positive regulation of cell cycle|
|response to oxidative stress|
|response to peptide hormone|
|nuclear speck|
|cellular response to drug|
|regulation of mitotic cell cycle phase transition|
|regulation of cell cycle phase transition|
|response to peptide|
|centrosome|
|response to toxic substance|
|DNA repair|
|posttranscriptional regulation of gene expression|
|response to inorganic substance|
|cellular response to organic cyclic compound|
|cellular response to organonitrogen compound|
|cellular response to hormone stimulus|
|regulation of mitotic cell cycle|
|cellular response to nitrogen compound|
|perinuclear region of cytoplasm|
|DNA metabolic process|
|regulation of cell cycle process|
|cellular response to DNA damage stimulus|
|regulation of cellular catabolic process|
|regulation of cell migration|
|nucleolus|
|cellular homeostasis|
|response to hormone|
|regulation of cell motility|
|response to organic cyclic compound|
|oxidation-reduction process|
|regulation of locomotion|
|regulation of cellular component movement|
|regulation of catabolic process|
|response to organonitrogen compound|
|endoplasmic reticulum|
|response to drug|
|cellular response to oxygen-containing compound|
|chromosome organization|
|response to nitrogen compound|
|regulation of cell cycle|
|cellular response to endogenous stimulus|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|mitochondrion|
|negative regulation of RNA metabolic process|
|RNA binding|
|negative regulation of nucleobase-containing compound metabolic process|
|DNA binding|
|negative regulation of macromolecule biosynthetic process|
|response to endogenous stimulus|
|negative regulation of cellular biosynthetic process|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|homeostatic process|
|RNA metabolic process|
|regulation of cell death|
|cellular response to stress|
|positive regulation of RNA metabolic process|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp535|Trimetrexate 0.03μM R08 exp535]]|-3.1|
|[[:results:exp235|Geldanamycin 0.01μM R05 exp235]]|-1.81|
|[[:results:exp189|Temozolomide 200μM R04 exp189]]|-1.78|
|[[:results:exp37|Wortmannin 0.5μM R00 exp37]]|1.85|
|[[:results:exp15|Cycloheximide 0.2μM R00 exp15]]|2.07|
|[[:results:exp31|Rifampicin 1μM R00 exp31]]|2.08|
|[[:results:exp10|CCCP 0.1μM R00 exp10]]|2.22|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 1/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/25|
|breast|1/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 13217
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.7 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='APEX1 Expression in NALM6 Cells: 7.7'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>