PPM1D [The Human Chemical-Genetic Interaction Map Project]

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======= PPM1D =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: PPM1D
  * **<color #00a2e8>Official Name</color>**: protein phosphatase, Mg2+/Mn2+ dependent 1D
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=8493|8493]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O15297|O15297]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=PPM1D&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PPM1D|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/605100|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. The expression of this gene is induced in a p53-dependent manner in response to various environmental stresses. While being induced by tumor suppressor protein TP53/p53, this phosphatase negatively regulates the activity of p38 MAP kinase, MAPK/p38, through which it reduces the phosphorylation of p53, and in turn suppresses p53-mediated transcription and apoptosis. This phosphatase thus mediates a feedback regulation of p38-p53 signaling that contributes to growth inhibition and the suppression of stress induced apoptosis. This gene is located in a chromosomal region known to be amplified in breast cancer. The amplification of this gene has been detected in both breast cancer cell line and primary breast tumors, which suggests a role of this gene in cancer development. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Involved in the negative regulation of p53 expression (PubMed:23242139). Required for the relief of p53-dependent checkpoint mediated cell cycle arrest. Binds to and dephosphorylates 'Ser-15' of TP53 and 'Ser-345' of CHEK1 which contributes to the functional inactivation of these proteins (PubMed:15870257, PubMed:16311512). Mediates MAPK14 dephosphorylation and inactivation (PubMed:21283629). Is also an important regulator of global heterochromatin silencing and critical in maintaining genome integrity (By similarity). {ECO:0000250|UniProtKB:Q9QZ67, ECO:0000269|PubMed:15870257, ECO:0000269|PubMed:16311512, ECO:0000269|PubMed:21283629, ECO:0000269|PubMed:23242139}.

<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'>
|PP2C|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|peptidyl-threonine dephosphorylation|
|magnesium-dependent protein serine/threonine phosphatase activity|
|mitogen-activated protein kinase binding|
|DNA methylation|
|DNA alkylation|
|chromatin silencing|
|chromatin organization involved in negative regulation of transcription|
|protein serine/threonine phosphatase activity|
|DNA methylation or demethylation|
|chromatin organization involved in regulation of transcription|
|DNA damage response, signal transduction by p53 class mediator|
|negative regulation of gene expression, epigenetic|
|DNA modification|
|signal transduction in response to DNA damage|
|signal transduction by p53 class mediator|
|G2/M transition of mitotic cell cycle|
|cell cycle G2/M phase transition|
|cellular response to starvation|
|gene silencing|
|transcription initiation from RNA polymerase II promoter|
|response to starvation|
|protein dephosphorylation|
|DNA-templated transcription, initiation|
|cellular response to nutrient levels|
|regulation of gene expression, epigenetic|
|macromolecule methylation|
|cellular response to extracellular stimulus|
|mitotic cell cycle phase transition|
|cell cycle phase transition|
|dephosphorylation|
|methylation|
|cellular response to external stimulus|
|protein serine/threonine kinase activity|
|response to radiation|
|transcription by RNA polymerase II|
|response to nutrient levels|
|response to extracellular stimulus|
|mitotic cell cycle process|
|transcription, DNA-templated|
|nucleic acid-templated transcription|
|RNA biosynthetic process|
|negative regulation of cell population proliferation|
|mitotic cell cycle|
|response to bacterium|
|chromatin organization|
|DNA metabolic process|
|cellular response to DNA damage stimulus|
|protein phosphorylation|
|cell cycle process|
|chromosome organization|
|nucleobase-containing compound biosynthetic process|
|response to abiotic stimulus|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|negative regulation of transcription, DNA-templated|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|phosphorylation|
|response to other organism|
|organic cyclic compound biosynthetic process|
|response to external biotic stimulus|
|response to biotic stimulus|
|negative regulation of RNA metabolic process|
|cell cycle|
|negative regulation of cellular macromolecule biosynthetic process|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|negative regulation of cellular biosynthetic process|
|negative regulation of biosynthetic process|
|regulation of cell population proliferation|
|cellular nitrogen compound biosynthetic process|
|RNA metabolic process|
|intracellular signal transduction|
|cellular response to stress|
|cellular macromolecule biosynthetic process|
|negative regulation of gene expression|
|macromolecule biosynthetic process|
|gene expression|
</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:exp294|Nutlin-3A 1.6μM R06 exp294]]|-2.88|
|[[:results:exp93|DABN racemic mixture R03 exp93]]|-2.27|
|[[:results:exp485|GSK626616 14μM R08 exp485]]|-2.21|
|[[:results:exp401|SNS-032 25μM R07 exp401]]|-2.12|
|[[:results:exp33|Rotenone 2μM R00 exp33]]|-2.05|
|[[:results:exp451|Atovaquone 15μM R08 exp451]]|-2.01|
|[[:results:exp536|Vitamin-D3 40μM R08 exp536]]|-1.88|
|[[:results:exp216|Erlotinib 10μM R05 exp216]]|1.7|
|[[:results:exp533|TNF-alpha 44ng/ml R08 exp533]]|1.7|
|[[:results:exp15|Cycloheximide 0.2μM R00 exp15]]|1.76|
|[[:results:exp18|Doxycycline 10μM R00 exp18]]|1.82|
|[[:results:exp432|YM155 0.001μM R08 exp432]]|1.94|
|[[:results:exp10|CCCP 0.1μM R00 exp10]]|1.95|
|[[:results:exp14|Cycloheximide 0.02μM R00 exp14]]|2.05|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:p:psma7|PSMA7]]|0.48|
|[[:human genes:n:narfl|NARFL]]|0.475|
|[[:human genes:r:rpl6|RPL6]]|0.468|
|[[:human genes:r:rad51|RAD51]]|0.467|
|[[:human genes:d:disp2|DISP2]]|0.458|
|[[:human genes:t:tceb3c|TCEB3C]]|0.457|
|[[:human genes:c:ciapin1|CIAPIN1]]|0.457|
|[[:human genes:p:psmb4|PSMB4]]|0.448|
|[[:human genes:r:rpl35|RPL35]]|0.447|
|[[:human genes:k:krt78|KRT78]]|0.446|
|[[:human genes:p:psmc1|PSMC1]]|0.444|
|[[:human genes:o:orc6|ORC6]]|0.443|
|[[:human genes:c:ccdc116|CCDC116]]|0.442|
|[[:human genes:c:cdc73|CDC73]]|0.442|
|[[:human genes:s:sf3a3|SF3A3]]|0.44|
|[[:human genes:w:wdr75|WDR75]]|0.44|
|[[:human genes:r:rpl8|RPL8]]|0.44|
|[[:human genes:s:smg7|SMG7]]|0.438|
|[[:human genes:a:acbd4|ACBD4]]|0.438|
|[[:human genes:t:ticrr|TICRR]]|0.437|
|[[:human genes:n:nop16|NOP16]]|0.435|
|[[:human genes:p:psma6|PSMA6]]|0.435|
|[[:human genes:t:tceb3cl2|TCEB3CL2]]|0.435|
|[[:human genes:t:tceb3cl|TCEB3CL]]|0.434|
|[[:human genes:n:ncl|NCL]]|0.434|
|[[:human genes:c:ctr9|CTR9]]|0.433|
|[[:human genes:t:terf2|TERF2]]|0.432|
|[[:human genes:p:psmc5|PSMC5]]|0.43|
|[[:human genes:t:terf1|TERF1]]|0.43|
|[[:human genes:p:pan3|PAN3]]|0.429|
|[[:human genes:r:rpl17|RPL17]]|0.429|
|[[:human genes:t:tsg101|TSG101]]|0.427|
|[[:human genes:c:ccdc64b|CCDC64B]]|0.426|
|[[:human genes:d:dtl|DTL]]|0.425|
|[[:human genes:c:copb1|COPB1]]|0.424|
|[[:human genes:c:cdt1|CDT1]]|0.423|
|[[:human genes:r:rplp1|RPLP1]]|0.422|
|[[:human genes:p:psmb1|PSMB1]]|0.421|
|[[:human genes:t:timeless|TIMELESS]]|0.42|
|[[:human genes:g:golga6l1|GOLGA6L1]]|0.417|
|[[:human genes:e:esco1|ESCO1]]|0.416|
|[[:human genes:x:xylt2|XYLT2]]|0.415|
|[[:human genes:e:exosc9|EXOSC9]]|0.414|
|[[:human genes:r:rps12|RPS12]]|0.412|
|[[:human genes:r:rps7|RPS7]]|0.412|
|[[:human genes:r:rpl14|RPL14]]|0.411|
|[[:human genes:z:znf574|ZNF574]]|0.411|
|[[:human genes:c:col2a1|COL2A1]]|0.41|
|[[:human genes:u:usp37|USP37]]|0.409|
|[[:human genes:t:tbc1d3l|TBC1D3L]]|0.408|
|[[:human genes:e:ebna1bp2|EBNA1BP2]]|0.408|
|[[:human genes:n:nol12|NOL12]]|0.408|
|[[:human genes:t:tbc1d3e|TBC1D3E]]|0.407|
|[[:human genes:t:tbc1d3k|TBC1D3K]]|0.407|
|[[:human genes:s:smg1|SMG1]]|0.406|
|[[:human genes:t:tbc1d3i|TBC1D3I]]|0.406|
|[[:human genes:c:cgb2|CGB2]]|0.406|
|[[:human genes:c:cdc6|CDC6]]|0.406|
|[[:human genes:p:psme3|PSME3]]|0.405|
|[[:human genes:r:rrn3|RRN3]]|0.404|
|[[:human genes:c:c14orf93|C14orf93]]|0.404|
|[[:human genes:t:tbc1d3f|TBC1D3F]]|0.401|
|[[:human genes:z:znf655|ZNF655]]|0.401|
|[[:human genes:c:cdca3|CDCA3]]|0.401|
|[[:human genes:t:taf1|TAF1]]|0.401|
|[[:human genes:i:ik|IK]]|0.4|
|[[:human genes:w:wdr87|WDR87]]|0.4|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 3/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 1353
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.55 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='PPM1D Expression in NALM6 Cells: 5.55'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>