PHLPP1 [The Human Chemical-Genetic Interaction Map Project]

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======= PHLPP1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: PHLPP1
  * **<color #00a2e8>Official Name</color>**: PH domain and leucine rich repeat protein phosphatase 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=23239|23239]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O60346|O60346]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=PHLPP1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PHLPP1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/609396|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a member of the serine/threonine phosphatase family. The encoded protein promotes apoptosis by dephosphorylating and inactivating the serine/threonine kinase Akt, and functions as a tumor suppressor in multiple types of cancer. Increased expression of this gene may also play a role in obesity and type 2 diabetes by interfering with Akt-mediated insulin signaling. [provided by RefSeq, Dec 2011]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRKCA (PubMed:15808505, PubMed:17386267, PubMed:18162466). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation (PubMed:18162466). Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis (PubMed:20513427). Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation (PubMed:21986499). Inhibits cancer cell proliferation and may act as a tumor suppressor (PubMed:19079341). Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). Involved in the hippocampus-dependent long-term memory formation (By similarity). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (By similarity). Involved in development and function of regulatory T-cells (By similarity). {ECO:0000250|UniProtKB:Q8CHE4, ECO:0000250|UniProtKB:Q9WTR8, ECO:0000269|PubMed:15808505, ECO:0000269|PubMed:17386267, ECO:0000269|PubMed:18162466, ECO:0000269|PubMed:19079341, ECO:0000269|PubMed:21986499, ECO:0000269|PubMed:24530606}.

<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|
|LRR 4|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|regulation of T cell anergy|
|regulation of lymphocyte anergy|
|regulation of T cell tolerance induction|
|regulation of tolerance induction|
|photoreceptor outer segment membrane|
|entrainment of circadian clock|
|regulation of p38MAPK cascade|
|negative regulation of protein kinase B signaling|
|photoreceptor inner segment|
|protein serine/threonine phosphatase activity|
|regulation of circadian rhythm|
|regulation of JNK cascade|
|protein dephosphorylation|
|regulation of protein kinase B signaling|
|regulation of stress-activated MAPK cascade|
|regulation of stress-activated protein kinase signaling cascade|
|nuclear membrane|
|dephosphorylation|
|negative regulation of intracellular signal transduction|
|regulation of cellular response to stress|
|regulation of MAPK cascade|
|apoptotic process|
|programmed cell death|
|cell death|
|negative regulation of signal transduction|
|negative regulation of cell communication|
|negative regulation of signaling|
|regulation of protein phosphorylation|
|regulation of response to stress|
|regulation of apoptotic process|
|regulation of programmed cell death|
|regulation of phosphorylation|
|negative regulation of response to stimulus|
|regulation of immune system process|
|regulation of cell death|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of intracellular signal transduction|
|regulation of protein modification 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:exp535|Trimetrexate 0.03μM R08 exp535]]|-2.6|
|[[:results:exp514|Phorbol-12-myristate-13-acetate 0.57μM R08 exp514]]|1.74|
|[[:results:exp122|Golgicide-A 4μM R03 exp122]]|1.98|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:w:wdr20|WDR20]]|0.473|
|[[:human genes:r:rrm1|RRM1]]|0.418|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^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>**: 4673
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.99 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='PHLPP1 Expression in NALM6 Cells: 5.99'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>