PCNA [The Human Chemical-Genetic Interaction Map Project]

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======= PCNA =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: PCNA
  * **<color #00a2e8>Official Name</color>**: proliferating cell nuclear antigen
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5111|5111]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P12004|P12004]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=PCNA&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PCNA|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/176740|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ubiquitinated and is involved in the RAD6-dependent DNA repair pathway. Two transcript variants encoding the same protein have been found for this gene. Pseudogenes of this gene have been described on chromosome 4 and on the X chromosome. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'- 5' exonuclease and 3'-phosphodiesterase, but not apurinic- apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways (PubMed:24939902). Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion. {ECO:0000269|PubMed:18719106, ECO:0000269|PubMed:19443450, ECO:0000269|PubMed:24939902}.

<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'>
|PCNA N|
|Rad1|
|Rad9|
|PCNA C|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|PCNA complex|
|DNA polymerase processivity factor activity|
|replisome|
|PCNA-p21 complex|
|purine-specific mismatch base pair DNA N-glycosylase activity|
|dinucleotide insertion or deletion binding|
|leading strand elongation|
|mitotic telomere maintenance via semi-conservative replication|
|positive regulation of deoxyribonuclease activity|
|base-excision repair, gap-filling|
|MutLalpha complex binding|
|nuclear lamina|
|positive regulation of nuclease activity|
|regulation of deoxyribonuclease activity|
|response to L-glutamate|
|nuclear replication fork|
|DNA strand elongation involved in DNA replication|
|estrous cycle|
|DNA polymerase binding|
|error-prone translesion synthesis|
|error-free translesion synthesis|
|DNA strand elongation|
|regulation of nuclease activity|
|nucleotide-excision repair, DNA gap filling|
|telomere maintenance via semi-conservative replication|
|replication fork|
|regulation of transcription involved in G1/S transition of mitotic cell cycle|
|histone acetyltransferase binding|
|cyclin-dependent protein kinase holoenzyme complex|
|liver regeneration|
|replication fork processing|
|mismatch repair|
|positive regulation of DNA replication|
|nucleotide-excision repair, DNA incision, 5-to lesion|
|DNA damage response, detection of DNA damage|
|base-excision repair|
|DNA-dependent DNA replication maintenance of fidelity|
|response to dexamethasone|
|nucleotide-excision repair, DNA incision|
|translesion synthesis|
|estrogen receptor binding|
|nuclear DNA replication|
|cell cycle DNA replication|
|DNA synthesis involved in DNA repair|
|postreplication repair|
|damaged DNA binding|
|DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest|
|receptor tyrosine kinase binding|
|intracellular signal transduction involved in G1 DNA damage checkpoint|
|signal transduction involved in mitotic DNA integrity checkpoint|
|signal transduction involved in mitotic G1 DNA damage checkpoint|
|signal transduction involved in mitotic cell cycle checkpoint|
|signal transduction involved in mitotic DNA damage checkpoint|
|mitotic G1 DNA damage checkpoint|
|mitotic G1/S transition checkpoint|
|G1 DNA damage checkpoint|
|response to cadmium ion|
|positive regulation of DNA repair|
|ovulation cycle|
|cellular response to hydrogen peroxide|
|signal transduction involved in DNA damage checkpoint|
|signal transduction involved in DNA integrity checkpoint|
|signal transduction involved in cell cycle checkpoint|
|animal organ regeneration|
|transcription-coupled nucleotide-excision repair|
|DNA damage response, signal transduction by p53 class mediator|
|positive regulation of cell cycle arrest|
|cellular response to UV|
|response to antineoplastic agent|
|mitotic DNA damage checkpoint|
|telomere maintenance|
|positive regulation of response to DNA damage stimulus|
|telomere organization|
|negative regulation of G1/S transition of mitotic cell cycle|
|signal transduction in response to DNA damage|
|mitotic DNA integrity checkpoint|
|negative regulation of cell cycle G1/S phase transition|
|regulation of cell cycle arrest|
|regulation of DNA replication|
|DNA biosynthetic process|
|nuclear chromosome, telomeric region|
|nucleotide-excision repair|
|cellular response to light stimulus|
|response to amino acid|
|chromatin|
|cellular response to antibiotic|
|response to hydrogen peroxide|
|G1/S transition of mitotic cell cycle|
|cell cycle G1/S phase transition|
|signal transduction by p53 class mediator|
|DNA-dependent DNA replication|
|regulation of DNA repair|
|liver development|
|hepaticobiliary system development|
|cellular response to reactive oxygen species|
|DNA damage checkpoint|
|response to estradiol|
|response to UV|
|DNA integrity checkpoint|
|response to glucocorticoid|
|regulation of G1/S transition of mitotic cell cycle|
|mitotic cell cycle checkpoint|
|regeneration|
|response to corticosteroid|
|regulation of cell cycle G1/S phase transition|
|cellular response to radiation|
|cellular response to xenobiotic stimulus|
|positive regulation of DNA metabolic process|
|response to ketone|
|cell cycle checkpoint|
|response to reactive oxygen species|
|negative regulation of mitotic cell cycle phase transition|
|cellular response to toxic substance|
|DNA replication|
|response to nutrient|
|regulation of response to DNA damage stimulus|
|negative regulation of cell cycle phase transition|
|cellular response to oxidative stress|
|mitotic cell cycle phase transition|
|rhythmic process|
|cell cycle phase transition|
|nuclear body|
|positive regulation of cell cycle process|
|nucleic acid phosphodiester bond hydrolysis|
|response to xenobiotic stimulus|
|response to antibiotic|
|negative regulation of mitotic cell cycle|
|response to light stimulus|
|cellular response to environmental stimulus|
|cellular response to abiotic stimulus|
|negative regulation of cell cycle process|
|response to steroid hormone|
|anatomical structure homeostasis|
|response to acid chemical|
|enzyme binding|
|regulation of DNA metabolic process|
|response to metal ion|
|positive regulation of cell cycle|
|response to oxidative stress|
|chromatin binding|
|cellular response to drug|
|gland development|
|regulation of mitotic cell cycle phase transition|
|response to radiation|
|regulation of cell cycle phase transition|
|centrosome|
|response to nutrient levels|
|response to toxic substance|
|DNA repair|
|heart development|
|response to extracellular stimulus|
|response to inorganic substance|
|negative regulation of cell cycle|
|mitotic cell cycle process|
|regulation of mitotic cell cycle|
|epithelial cell differentiation|
|mitotic cell cycle|
|protein ubiquitination|
|detection of stimulus|
|viral process|
|regulation of cellular response to stress|
|DNA metabolic process|
|regulation of cell cycle process|
|positive regulation of hydrolase activity|
|protein modification by small protein conjugation|
|cellular response to DNA damage stimulus|
|symbiotic process|
|interspecies interaction between organisms|
|multicellular organismal reproductive process|
|multicellular organism reproduction|
|response to lipid|
|negative regulation of transcription by RNA polymerase II|
|circulatory system development|
|cellular homeostasis|
|response to hormone|
|response to organic cyclic compound|
|protein modification by small protein conjugation or removal|
|cell cycle process|
|response to organonitrogen compound|
|response to drug|
|cellular response to oxygen-containing compound|
|chromosome organization|
|identical protein binding|
|response to nitrogen compound|
|nucleobase-containing compound biosynthetic process|
|epithelium development|
|response to abiotic stimulus|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|regulation of cell cycle|
|negative regulation of transcription, DNA-templated|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|regulation of hydrolase activity|
|organic cyclic compound biosynthetic process|
|negative regulation of RNA metabolic process|
|cell cycle|
|negative regulation of cellular macromolecule biosynthetic process|
|reproductive process|
|reproduction|
|positive regulation of catalytic activity|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|response to endogenous stimulus|
|regulation of response to stress|
|negative regulation of cellular biosynthetic process|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|cellular nitrogen compound biosynthetic process|
|homeostatic process|
|intracellular signal transduction|
|cellular response to stress|
|cellular macromolecule biosynthetic process|
|negative regulation of gene expression|
|tissue development|
|macromolecule biosynthetic process|
|positive regulation of molecular function|
|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='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:exp211|AICAR 240μM R05 exp211]]|-2.14|
|[[:results:exp345|Cidofovir 10μM R07 exp345]]|-2.11|
|[[:results:exp179|Combretastatin A4 0.002 to 0.003μM day4 R04 exp179]]|-1.74|
|[[:results:exp108|Vinblastine 0.2μM R03 exp108]]|-1.73|
|[[:results:exp156|UNC2400 2μM R03 exp156]]|1.71|
|[[:results:exp344|Chlorpromazine 10μM R07 exp344]]|1.73|
|[[:results:exp230|Epigallocatechin gallate 20μM R05 exp230]]|1.76|
|[[:results:exp352|Dexamethasone 0.006 to 0.015μM on day4 R07 exp352]]|1.81|
|[[:results:exp336|Asunaprenir 3μM R07 exp336]]|1.82|
|[[:results:exp130|JQ1 0.01μM R03 exp130]]|2.01|
|[[:results:exp372|Ibrutinib 1μM R07 exp372]]|2.09|
|[[:results:exp351|Dexamethasone 0.006μM R07 exp351]]|2.11|
|[[:results:exp421|VHL-ligand-1 20μM R07 exp421]]|2.15|
|[[:results:exp219|A-395N 10μM R05 exp219]]|2.21|
|[[:results:exp144|PFI-3 10μM R03 exp144]]|2.33|
|[[:results:exp376|Losmapimod 1μM R07 exp376]]|2.47|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:g:golga6l1|GOLGA6L1]]|0.708|
|[[:human genes:p:prim1|PRIM1]]|0.466|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 724/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|1/1|
|909776.0|1/1|
|bile duct|28/28|
|blood|28/28|
|bone|25/25|
|breast|33/33|
|central nervous system|56/56|
|cervix|4/4|
|colorectal|17/17|
|esophagus|13/13|
|fibroblast|1/1|
|gastric|15/15|
|kidney|21/21|
|liver|20/20|
|lung|75/75|
|lymphocyte|14/14|
|ovary|26/26|
|pancreas|24/24|
|peripheral nervous system|16/16|
|plasma cell|15/15|
|prostate|1/1|
|skin|24/24|
|soft tissue|6/7|
|thyroid|2/2|
|upper aerodigestive|22/22|
|urinary tract|29/29|
|uterus|5/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 12
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 8.38 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='PCNA Expression in NALM6 Cells: 8.38'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>