PAK2 [The Human Chemical-Genetic Interaction Map Project]

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======= PAK2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: PAK2
  * **<color #00a2e8>Official Name</color>**: p21 (RAC1) activated kinase 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5062|5062]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q13177|Q13177]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=PAK2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PAK2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/605022|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The p21 activated kinases (PAK) are critical effectors that link Rho GTPases to cytoskeleton reorganization and nuclear signaling. The PAK proteins are a family of serine/threonine kinases that serve as targets for the small GTP binding proteins, CDC42 and RAC1, and have been implicated in a wide range of biological activities. The protein encoded by this gene is activated by proteolytic cleavage during caspase-mediated apoptosis, and may play a role in regulating the apoptotic events in the dying cell. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation. Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Full-length PAK2 stimulates cell survival and cell growth. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Phosphorylates JUN and plays an important role in EGF- induced cell proliferation. Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP. Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis. On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway. Caspase- activated PAK2 phosphorylates MKNK1 and reduces cellular translation. {ECO:0000269|PubMed:12853446, ECO:0000269|PubMed:15234964, ECO:0000269|PubMed:16617111, ECO:0000269|PubMed:19923322, ECO:0000269|PubMed:21177766, ECO:0000269|PubMed:21317288, ECO:0000269|PubMed:21724829, ECO:0000269|PubMed:9171063}.

<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'>
|Pkinase|
|Pkinase Tyr|
|PBD|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis|
|regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis|
|protein tyrosine kinase activator activity|
|small GTPase binding|
|negative regulation of execution phase of apoptosis|
|dendritic spine development|
|regulation of defense response to virus by virus|
|regulation of execution phase of apoptosis|
|interleukin-12-mediated signaling pathway|
|cellular response to interleukin-12|
|positive regulation of extrinsic apoptotic signaling pathway|
|response to interleukin-12|
|T cell costimulation|
|Rac GTPase binding|
|lymphocyte costimulation|
|positive regulation of protein tyrosine kinase activity|
|vascular endothelial growth factor receptor signaling pathway|
|negative regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|regulation of protein tyrosine kinase activity|
|negative regulation of cysteine-type endopeptidase activity|
|dendrite development|
|stimulatory C-type lectin receptor signaling pathway|
|innate immune response activating cell surface receptor signaling pathway|
|stress-activated protein kinase signaling cascade|
|regulation of extrinsic apoptotic signaling pathway|
|Fc-epsilon receptor signaling pathway|
|positive regulation of apoptotic signaling pathway|
|peptidyl-serine phosphorylation|
|T cell receptor signaling pathway|
|positive regulation of peptidyl-tyrosine phosphorylation|
|protein autophosphorylation|
|peptidyl-serine modification|
|positive regulation of T cell activation|
|regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|positive regulation of leukocyte cell-cell adhesion|
|negative regulation of protein kinase activity|
|innate immune response-activating signal transduction|
|protein kinase activity|
|Fc receptor signaling pathway|
|regulation of cysteine-type endopeptidase activity|
|negative regulation of endopeptidase activity|
|negative regulation of kinase activity|
|regulation of peptidyl-tyrosine phosphorylation|
|postsynaptic density|
|positive regulation of cell-cell adhesion|
|negative regulation of peptidase activity|
|activation of innate immune response|
|negative regulation of transferase activity|
|antigen receptor-mediated signaling pathway|
|regulation of leukocyte cell-cell adhesion|
|cadherin binding|
|regulation of T cell activation|
|activation of protein kinase activity|
|positive regulation of innate immune response|
|glutamatergic synapse|
|negative regulation of proteolysis|
|positive regulation of lymphocyte activation|
|positive regulation of response to biotic stimulus|
|protein serine/threonine kinase activity|
|signal transduction by protein phosphorylation|
|regulation of apoptotic signaling pathway|
|regulation of cell-cell adhesion|
|positive regulation of cell adhesion|
|positive regulation of leukocyte activation|
|negative regulation of protein phosphorylation|
|regulation of endopeptidase activity|
|positive regulation of cell activation|
|negative regulation of phosphorylation|
|regulation of peptidase activity|
|immune response-activating cell surface receptor signaling pathway|
|regulation of innate immune response|
|negative regulation of hydrolase activity|
|protein kinase binding|
|positive regulation of defense response|
|immune response-regulating cell surface receptor signaling pathway|
|positive regulation of multi-organism process|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|regulation of lymphocyte activation|
|regulation of response to biotic stimulus|
|positive regulation of protein kinase activity|
|cellular response to organic cyclic compound|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|immune response-activating signal transduction|
|positive regulation of kinase activity|
|negative regulation of protein modification process|
|immune response-regulating signaling pathway|
|positive regulation of response to external stimulus|
|regulation of leukocyte activation|
|activation of immune response|
|regulation of cell activation|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|positive regulation of transferase activity|
|neuron projection development|
|regulation of growth|
|cytokine-mediated signaling pathway|
|regulation of cell adhesion|
|perinuclear region of cytoplasm|
|positive regulation of cell death|
|viral process|
|enzyme linked receptor protein signaling pathway|
|regulation of proteolysis|
|regulation of MAPK cascade|
|regulation of defense response|
|regulation of multi-organism process|
|symbiotic process|
|negative regulation of catalytic activity|
|regulation of protein kinase activity|
|neuron development|
|interspecies interaction between organisms|
|positive regulation of immune response|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|response to organic cyclic compound|
|apoptotic process|
|cell migration|
|protein phosphorylation|
|regulation of transferase activity|
|negative regulation of cell death|
|cellular response to cytokine stimulus|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|negative regulation of cellular protein metabolic process|
|programmed cell death|
|positive regulation of phosphorylation|
|identical protein binding|
|localization of cell|
|cell motility|
|cell death|
|regulation of response to external stimulus|
|response to cytokine|
|negative regulation of protein metabolic process|
|plasma membrane bounded cell projection organization|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|negative regulation of molecular function|
|regulation of immune response|
|positive regulation of immune system process|
|cell projection organization|
|positive regulation of protein modification process|
|regulation of hydrolase activity|
|phosphorylation|
|locomotion|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|regulation of response to stress|
|ATP binding|
|generation of neurons|
|regulation of apoptotic process|
|movement of cell or subcellular component|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|neurogenesis|
|cell development|
|positive regulation of signal transduction|
|regulation of immune system process|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|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='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:exp512|Olaparib 4μM R08 exp512]]|1.78|
</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: 4/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|1/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|1/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|2/75|
|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>**: 4845
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.65 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='PAK2 Expression in NALM6 Cells: 7.65'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>