PARP1 [The Human Chemical-Genetic Interaction Map Project]

This page is read only. You can view the source, but not change it. Ask your administrator if you think this is wrong.
======= PARP1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: PARP1
  * **<color #00a2e8>Official Name</color>**: poly(ADP-ribose) polymerase 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=142|142]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P09874|P09874]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=PARP1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PARP1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/173870|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272). Mediates the poly(ADP-ribosyl)ation of APLF and CHFR (PubMed:17396150). Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production (PubMed:17177976). Required for PARP9 and DTX3L recruitment to DNA damage sites (PubMed:23230272). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272). Mediates serine ADP-ribosylation of target proteins following interaction with HPF1; HPF1 conferring serine specificity (PubMed:28190768). Mediates the poly(ADP-ribosyl)ation of histones in a HPF1-dependent manner (PubMed:27067600). Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy- consuming (PubMed:27257257). {ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:17396150, ECO:0000269|PubMed:18172500, ECO:0000269|PubMed:19344625, ECO:0000269|PubMed:19661379, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:27257257, ECO:0000269|PubMed:28190768}.

<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'>
|PARP|
|PARP reg|
|PADR1|
|BRCT|
|WGR|
|zf-PARP|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|peptidyl-glutamic acid poly-ADP-ribosylation|
|positive regulation of myofibroblast differentiation|
|positive regulation of single strand break repair|
|DNA ADP-ribosylation|
|NAD DNA ADP-ribosyltransferase activity|
|regulation of single strand break repair|
|negative regulation of ATP biosynthetic process|
|response to aldosterone|
|ATP generation from poly-ADP-D-ribose|
|regulation of myofibroblast differentiation|
|peptidyl-serine ADP-ribosylation|
|mitochondrial DNA repair|
|negative regulation of purine nucleotide biosynthetic process|
|negative regulation of nucleotide biosynthetic process|
|regulation of SMAD protein complex assembly|
|regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway|
|protein poly-ADP-ribosylation|
|mitochondrial DNA metabolic process|
|positive regulation of double-strand break repair via homologous recombination|
|positive regulation of mitochondrial depolarization|
|protein auto-ADP-ribosylation|
|positive regulation of membrane depolarization|
|positive regulation of intracellular estrogen receptor signaling pathway|
|positive regulation of SMAD protein signal transduction|
|positive regulation of intracellular steroid hormone receptor signaling pathway|
|protein autoprocessing|
|protein ADP-ribosylase activity|
|regulation of ATP biosynthetic process|
|negative regulation of purine nucleotide metabolic process|
|site of DNA damage|
|mitochondrial genome maintenance|
|negative regulation of nucleotide metabolic process|
|signal transduction involved in regulation of gene expression|
|nucleotide-excision repair, preincision complex stabilization|
|regulation of mitochondrial depolarization|
|regulation of SMAD protein signal transduction|
|nucleotide-excision repair, DNA duplex unwinding|
|nucleotide-excision repair, DNA incision, 3-to lesion|
|R-SMAD binding|
|nucleotide-excision repair, DNA damage recognition|
|cellular response to zinc ion|
|regulation of DNA methylation|
|macrophage differentiation|
|positive regulation of transcription regulatory region DNA binding|
|negative regulation of ATP metabolic process|
|global genome nucleotide-excision repair|
|regulation of oxidative stress-induced neuron death|
|negative regulation of telomere maintenance via telomere lengthening|
|NAD+ ADP-ribosyltransferase activity|
|regulation of oxidative stress-induced intrinsic apoptotic signaling pathway|
|nucleotide-excision repair, preincision complex assembly|
|peptidyl-glutamic acid modification|
|protein ADP-ribosylation|
|positive regulation of cardiac muscle hypertrophy|
|positive regulation of double-strand break repair|
|positive regulation of muscle hypertrophy|
|response to mineralocorticoid|
|negative regulation of telomere maintenance|
|nucleotide-excision repair, DNA incision, 5-to lesion|
|regulation of purine nucleotide biosynthetic process|
|cellular response to amyloid-beta|
|DNA damage response, detection of DNA damage|
|positive regulation of DNA recombination|
|regulation of nucleotide biosynthetic process|
|nucleotide-excision repair, DNA incision|
|NAD binding|
|regulation of intracellular estrogen receptor signaling pathway|
|estrogen receptor binding|
|regulation of membrane depolarization|
|protein-DNA complex|
|regulation of double-strand break repair via homologous recombination|
|response to amyloid-beta|
|regulation of transcription regulatory region DNA binding|
|response to zinc ion|
|response to gamma radiation|
|regulation of cardiac muscle hypertrophy|
|positive regulation of DNA binding|
|site of double-strand break|
|regulation of muscle hypertrophy|
|regulation of telomere maintenance via telomere lengthening|
|regulation of oxidative stress-induced cell death|
|positive regulation of DNA repair|
|regulation of mitochondrial membrane potential|
|positive regulation of protein localization to nucleus|
|regulation of cellular response to oxidative stress|
|regulation of intracellular steroid hormone receptor signaling pathway|
|regulation of double-strand break repair|
|regulation of telomere maintenance|
|cellular response to UV|
|regulation of response to oxidative stress|
|regulation of muscle adaptation|
|DNA modification|
|negative regulation of small molecule metabolic process|
|positive regulation of neuron death|
|double-strand break repair via homologous recombination|
|telomere maintenance|
|recombinational repair|
|positive regulation of response to DNA damage stimulus|
|telomere organization|
|transforming growth factor beta receptor signaling pathway|
|positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|regulation of DNA recombination|
|protein N-terminus binding|
|nuclear chromosome, telomeric region|
|DNA duplex unwinding|
|nucleotide-excision repair|
|myeloid leukocyte differentiation|
|histone deacetylase binding|
|cellular response to light stimulus|
|regulation of protein localization to nucleus|
|regulation of purine nucleotide metabolic process|
|regulation of nucleotide metabolic process|
|DNA geometric change|
|regulation of ATP metabolic process|
|negative regulation of DNA metabolic process|
|regulation of DNA repair|
|regulation of DNA binding|
|negative regulation of chromosome organization|
|response to UV|
|response to ionizing radiation|
|cellular response to transforming growth factor beta stimulus|
|protein processing|
|regulation of intrinsic apoptotic signaling pathway|
|response to corticosteroid|
|response to transforming growth factor beta|
|cellular response to insulin stimulus|
|cellular response to radiation|
|positive regulation of binding|
|nuclear envelope|
|double-strand break repair|
|cellular response to metal ion|
|response to ketone|
|positive regulation of DNA metabolic process|
|transmembrane receptor protein serine/threonine kinase signaling pathway|
|peptidyl-serine modification|
|protein-DNA complex assembly|
|ATP metabolic process|
|transcription factor complex|
|regulation of neuron apoptotic process|
|regulation of response to DNA damage stimulus|
|myeloid cell differentiation|
|cellular response to inorganic substance|
|DNA recombination|
|protein maturation|
|response to insulin|
|response to alcohol|
|regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|regulation of muscle system process|
|cellular response to oxidative stress|
|protein-DNA complex subunit organization|
|positive regulation of protein complex assembly|
|cellular response to peptide hormone stimulus|
|DNA conformation change|
|nucleic acid phosphodiester bond hydrolysis|
|response to light stimulus|
|regulation of neuron death|
|RNA polymerase II regulatory region sequence-specific DNA binding|
|cellular response to abiotic stimulus|
|cellular response to environmental stimulus|
|positive regulation of cellular protein localization|
|cellular response to peptide|
|response to steroid hormone|
|leukocyte differentiation|
|transcription factor binding|
|anatomical structure homeostasis|
|enzyme binding|
|regulation of chromosome organization|
|regulation of DNA metabolic process|
|response to metal ion|
|negative regulation of organelle organization|
|regulation of binding|
|response to oxidative stress|
|response to peptide hormone|
|regulation of apoptotic signaling pathway|
|regulation of small molecule metabolic process|
|regulation of membrane potential|
|response to radiation|
|mitochondrion organization|
|DNA-binding transcription activator activity, RNA polymerase II-specific|
|regulation of protein complex assembly|
|protein kinase binding|
|response to peptide|
|transcription by RNA polymerase II|
|cellular response to growth factor stimulus|
|DNA repair|
|positive regulation of cellular component biogenesis|
|response to growth factor|
|response to inorganic substance|
|regulation of cellular protein localization|
|hemopoiesis|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|regulation of system process|
|protein-containing complex|
|cellular response to organonitrogen compound|
|cellular response to hormone stimulus|
|hematopoietic or lymphoid organ development|
|transcription, DNA-templated|
|nucleic acid-templated transcription|
|immune system development|
|RNA biosynthetic process|
|cellular response to nitrogen compound|
|detection of stimulus|
|positive regulation of cell death|
|negative regulation of cellular component organization|
|enzyme linked receptor protein signaling pathway|
|regulation of cellular response to stress|
|DNA metabolic process|
|cellular response to DNA damage stimulus|
|ion homeostasis|
|zinc ion binding|
|cellular protein-containing complex assembly|
|response to lipid|
|nucleolus|
|negative regulation of transcription by RNA polymerase II|
|peptidyl-amino acid modification|
|response to hormone|
|regulation of cellular localization|
|response to organic cyclic compound|
|apoptotic process|
|regulation of cellular component biogenesis|
|positive regulation of cell differentiation|
|response to organonitrogen compound|
|carbohydrate derivative metabolic process|
|regulation of protein localization|
|programmed cell death|
|cellular response to oxygen-containing compound|
|chromosome organization|
|identical protein binding|
|response to nitrogen compound|
|cell death|
|nucleobase-containing compound biosynthetic process|
|chemical homeostasis|
|response to abiotic stimulus|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|negative regulation of transcription, DNA-templated|
|positive regulation of cellular component organization|
|positive regulation of transcription by RNA polymerase II|
|cellular response to endogenous stimulus|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|mitochondrion|
|proteolysis|
|regulation of organelle organization|
|organic cyclic compound biosynthetic process|
|negative regulation of RNA metabolic process|
|positive regulation of developmental process|
|negative regulation of cellular macromolecule biosynthetic process|
|RNA binding|
|negative regulation of nucleobase-containing compound metabolic process|
|DNA binding|
|negative regulation of macromolecule biosynthetic process|
|response to endogenous stimulus|
|regulation of response to stress|
|negative regulation of cellular biosynthetic process|
|regulation of apoptotic process|
|positive regulation of transcription, DNA-templated|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of programmed cell death|
|cellular nitrogen compound biosynthetic process|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|homeostatic process|
|positive regulation of signal transduction|
|RNA metabolic process|
|regulation of cell death|
|cellular response to stress|
|cellular macromolecule biosynthetic process|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|macromolecule biosynthetic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|protein-containing complex subunit organization|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|membrane|
|gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' 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:exp189|Temozolomide 200μM R04 exp189]]|-2.85|
|[[:results:exp270|Campthothecin 0.001μM R06 exp270]]|-2.44|
|[[:results:exp350|Deferoxamine 11μM R07 exp350]]|-2.14|
|[[:results:exp423|Zebularine 20μM R07 exp423]]|-1.94|
|[[:results:exp7|Bortezomib 0.05μM R00 exp7]]|-1.86|
|[[:results:exp98|BI-6727 0.04μM R03 exp98]]|1.71|
|[[:results:exp520|Rucaparib 6.5μM R08 exp520]]|7.51|
|[[:results:exp512|Olaparib 4μM R08 exp512]]|7.76|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:a:adprhl2|ADPRHL2]]|0.434|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/726
^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|0/33|
|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>**: 3617
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 9.61 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='PARP1 Expression in NALM6 Cells: 9.61'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>