======= PAK4 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: PAK4
  * **<color #00a2e8>Official Name</color>**: p21 (RAC1) activated kinase 4
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=10298|10298]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O96013|O96013]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=PAK4&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PAK4|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/605451|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  PAK proteins, a family of serine/threonine p21-activating kinases, include PAK1, PAK2, PAK3 and PAK4. PAK proteins are critical effectors that link Rho GTPases to cytoskeleton reorganization and nuclear signaling. They serve as targets for the small GTP binding proteins Cdc42 and Rac and have been implicated in a wide range of biological activities. PAK4 interacts specifically with the GTP-bound form of Cdc42Hs and weakly activates the JNK family of MAP kinases. PAK4 is a mediator of filopodia formation and may play a role in the reorganization of the actin cytoskeleton. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [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 migration, growth, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN. {ECO:0000269|PubMed:11278822, ECO:0000269|PubMed:11313478, ECO:0000269|PubMed:14560027, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:20507994, ECO:0000269|PubMed:20631255, ECO:0000269|PubMed:20805321, ECO:0000269|PubMed:26607847}.

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

<modal id='GO_terms' size='lg' title='GO Terms'>
|cadherin binding involved in cell-cell adhesion|
|dendritic spine development|
|negative regulation of endothelial cell apoptotic process|
|negative regulation of epithelial cell apoptotic process|
|regulation of endothelial cell apoptotic process|
|Rac GTPase binding|
|regulation of epithelial cell apoptotic process|
|dendrite development|
|cell-cell adherens junction|
|stress-activated protein kinase signaling cascade|
|positive regulation of angiogenesis|
|positive regulation of vasculature development|
|protein kinase activity|
|regulation of angiogenesis|
|regulation of vasculature development|
|activation of protein kinase activity|
|protein serine/threonine kinase activity|
|signal transduction by protein phosphorylation|
|focal adhesion|
|regulation of cell growth|
|cell-cell adhesion|
|positive regulation of protein kinase activity|
|cellular response to organic cyclic compound|
|cell population proliferation|
|positive regulation of kinase activity|
|positive regulation of transferase activity|
|neuron projection development|
|regulation of growth|
|regulation of MAPK cascade|
|regulation of protein kinase activity|
|neuron development|
|regulation of kinase activity|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|response to organic cyclic compound|
|apoptotic process|
|cell adhesion|
|biological adhesion|
|cell migration|
|protein phosphorylation|
|regulation of transferase activity|
|Golgi apparatus|
|negative regulation of cell death|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|programmed cell death|
|positive regulation of phosphorylation|
|regulation of anatomical structure morphogenesis|
|cell motility|
|localization of cell|
|cell death|
|cytoskeleton organization|
|plasma membrane bounded cell projection organization|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|cell projection organization|
|positive regulation of protein modification process|
|phosphorylation|
|locomotion|
|cell cycle|
|positive regulation of developmental process|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|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|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|positive regulation of molecular function|
|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='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:exp538|ZLN024 50μM R08 exp538]]|-1.87|
|[[:results:exp111|R-DABN 8μM R03 exp111]]|-1.82|
|[[:results:exp468|CB-5083 0.4μM R08 exp468]]|-1.71|
|[[:results:exp177|Apcin 25μM plus proTAME 2μM R04 exp177]]|2.06|
|[[:results:exp533|TNF-alpha 44ng/ml R08 exp533]]|2.1|
</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: 1/739
^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|1/17|
|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>**: 3806
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 4.59 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='PAK4 Expression in NALM6 Cells: 4.59'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>