======= PAK1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: PAK1
  * **<color #00a2e8>Official Name</color>**: p21 (RAC1) activated kinase 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5058|5058]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q13153|Q13153]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=PAK1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PAK1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/602590|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a family member of serine/threonine p21-activating kinases, known as PAK proteins. These proteins are critical effectors that link RhoGTPases to cytoskeleton reorganization and nuclear signaling, and they serve as targets for the small GTP binding proteins Cdc42 and Rac. This specific family member regulates cell motility and morphology. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2. Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus. In podocytes, promotes NR3C2 nuclear localization. Required for atypical chemokine receptor ACKR2- induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In synapses, seems to mediate the regulation of F- actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation. Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion (PubMed:25766321). {ECO:0000269|PubMed:10551809, ECO:0000269|PubMed:11733498, ECO:0000269|PubMed:12624090, ECO:0000269|PubMed:12876277, ECO:0000269|PubMed:14585966, ECO:0000269|PubMed:15611088, ECO:0000269|PubMed:15831477, ECO:0000269|PubMed:15833848, ECO:0000269|PubMed:16278681, ECO:0000269|PubMed:17726028, ECO:0000269|PubMed:17989089, ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:23633677, ECO:0000269|PubMed:25766321, ECO:0000269|PubMed:8805275, ECO:0000269|PubMed:9032240, ECO:0000269|PubMed:9395435, ECO:0000269|PubMed:9528787}.

<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'>
|negative regulation of cell proliferation involved in contact inhibition|
|contact inhibition|
|negative regulation of cell growth involved in cardiac muscle cell development|
|invadopodium|
|positive regulation of fibroblast migration|
|hepatocyte growth factor receptor signaling pathway|
|positive regulation of intracellular estrogen receptor signaling pathway|
|positive regulation of intracellular steroid hormone receptor signaling pathway|
|positive regulation of vascular associated smooth muscle cell migration|
|negative regulation of cardiac muscle cell differentiation|
|regulation of cell growth involved in cardiac muscle cell development|
|negative regulation of cardiocyte differentiation|
|positive regulation of insulin receptor signaling pathway|
|regulation of vascular associated smooth muscle cell migration|
|negative regulation of heart growth|
|negative regulation of cardiac muscle tissue growth|
|positive regulation of cellular response to insulin stimulus|
|negative regulation of cardiac muscle hypertrophy|
|negative regulation of muscle hypertrophy|
|regulation of fibroblast migration|
|positive regulation of microtubule polymerization|
|positive regulation of protein targeting to membrane|
|negative regulation of organ growth|
|negative regulation of cardiac muscle tissue development|
|positive regulation of vascular smooth muscle cell proliferation|
|positive regulation of microtubule polymerization or depolymerization|
|regulation of cardiac muscle cell differentiation|
|positive regulation of smooth muscle cell migration|
|regulation of protein targeting to membrane|
|negative regulation of striated muscle cell differentiation|
|regulation of intracellular estrogen receptor signaling pathway|
|positive regulation of axon extension|
|intercalated disc|
|negative regulation of striated muscle tissue development|
|negative regulation of muscle organ development|
|regulation of vascular smooth muscle cell proliferation|
|regulation of cardiocyte differentiation|
|negative regulation of muscle tissue development|
|regulation of microtubule polymerization|
|positive regulation of stress fiber assembly|
|Rac GTPase binding|
|T cell costimulation|
|lymphocyte costimulation|
|negative regulation of muscle cell differentiation|
|regulation of cardiac muscle hypertrophy|
|regulation of cardiac muscle tissue growth|
|regulation of muscle hypertrophy|
|regulation of smooth muscle cell migration|
|positive regulation of actin filament bundle assembly|
|collagen binding|
|regulation of heart growth|
|regulation of insulin receptor signaling pathway|
|actin cytoskeleton reorganization|
|positive regulation of JUN kinase activity|
|regulation of cellular response to insulin stimulus|
|regulation of intracellular steroid hormone receptor signaling pathway|
|regulation of stress fiber assembly|
|regulation of cardiac muscle tissue development|
|regulation of microtubule polymerization or depolymerization|
|actin filament|
|regulation of protein targeting|
|positive regulation of smooth muscle cell proliferation|
|regulation of muscle adaptation|
|positive regulation of axonogenesis|
|regulation of JUN kinase activity|
|ephrin receptor signaling pathway|
|regulation of actomyosin structure organization|
|ruffle|
|regulation of actin filament bundle assembly|
|regulation of organ growth|
|ruffle membrane|
|regulation of axon extension|
|regulation of striated muscle cell differentiation|
|cerebellum development|
|positive regulation of peptidyl-serine phosphorylation|
|negative regulation of developmental growth|
|regulation of extent of cell growth|
|metencephalon development|
|stimulatory C-type lectin receptor signaling pathway|
|innate immune response activating cell surface receptor signaling pathway|
|establishment of cell polarity|
|positive regulation of protein localization to membrane|
|chromosome|
|positive regulation of protein polymerization|
|branching morphogenesis of an epithelial tube|
|Z disc|
|regulation of striated muscle tissue development|
|regulation of smooth muscle cell proliferation|
|regulation of muscle tissue development|
|immune response-regulating cell surface receptor signaling pathway involved in phagocytosis|
|Fc-gamma receptor signaling pathway involved in phagocytosis|
|regulation of muscle organ development|
|regulation of peptidyl-serine phosphorylation|
|Fc receptor mediated stimulatory signaling pathway|
|positive regulation of JNK cascade|
|Fc-gamma receptor signaling pathway|
|stress-activated protein kinase signaling cascade|
|hindbrain development|
|regulation of muscle cell differentiation|
|positive regulation of intracellular protein transport|
|positive regulation of cell morphogenesis involved in differentiation|
|morphogenesis of a branching epithelium|
|chromatin remodeling|
|cellular response to insulin stimulus|
|positive regulation of cell growth|
|positive regulation of stress-activated MAPK cascade|
|positive regulation of stress-activated protein kinase signaling cascade|
|morphogenesis of a branching structure|
|positive regulation of developmental growth|
|cell-cell junction|
|Fc-epsilon receptor signaling pathway|
|T cell receptor signaling pathway|
|lamellipodium|
|regulation of cell size|
|negative regulation of cell growth|
|regulation of axonogenesis|
|regulation of JNK cascade|
|regulation of protein localization to membrane|
|regulation of microtubule cytoskeleton organization|
|protein autophosphorylation|
|establishment or maintenance of cell polarity|
|positive regulation of supramolecular fiber organization|
|positive regulation of T cell activation|
|positive regulation of intracellular transport|
|positive regulation of leukocyte cell-cell adhesion|
|positive regulation of cytoskeleton organization|
|regulation of microtubule-based process|
|regulation of protein polymerization|
|response to insulin|
|regulation of intracellular protein transport|
|innate immune response-activating signal transduction|
|regulation of stress-activated MAPK cascade|
|regulation of muscle system process|
|regulation of stress-activated protein kinase signaling cascade|
|protein kinase activity|
|nuclear membrane|
|Fc receptor signaling pathway|
|negative regulation of growth|
|positive regulation of protein complex assembly|
|positive regulation of cell-cell adhesion|
|activation of innate immune response|
|positive regulation of growth|
|regulation of actin filament organization|
|positive regulation of MAP kinase activity|
|cellular response to peptide hormone stimulus|
|positive regulation of neuron projection development|
|antigen receptor-mediated signaling pathway|
|axon|
|regulation of leukocyte cell-cell adhesion|
|regulation of cell morphogenesis involved in differentiation|
|epithelial tube morphogenesis|
|regulation of T cell activation|
|positive regulation of cellular protein localization|
|cellular response to peptide|
|activation of protein kinase activity|
|regulation of developmental growth|
|phagocytosis|
|negative regulation of cell development|
|positive regulation of protein serine/threonine kinase activity|
|positive regulation of innate immune response|
|regulation of MAP kinase activity|
|regulation of actin cytoskeleton organization|
|response to hypoxia|
|regulation of intracellular transport|
|regulation of supramolecular fiber organization|
|response to decreased oxygen levels|
|positive regulation of lymphocyte activation|
|positive regulation of response to biotic stimulus|
|protein serine/threonine kinase activity|
|positive regulation of neuron differentiation|
|MAPK cascade|
|regulation of cellular component size|
|response to oxygen levels|
|positive regulation of cell projection organization|
|regulation of actin filament-based process|
|response to peptide hormone|
|signal transduction by protein phosphorylation|
|regulation of cell-cell adhesion|
|positive regulation of leukocyte activation|
|positive regulation of cell adhesion|
|focal adhesion|
|regulation of cell growth|
|positive regulation of cell activation|
|dendrite|
|positive regulation of protein transport|
|morphogenesis of an epithelium|
|immune response-activating cell surface receptor signaling pathway|
|regulation of protein complex assembly|
|regulation of innate immune response|
|positive regulation of establishment of protein localization|
|protein kinase binding|
|positive regulation of neurogenesis|
|response to peptide|
|positive regulation of defense response|
|wound healing|
|neuron projection morphogenesis|
|immune response-regulating cell surface receptor signaling pathway|
|plasma membrane bounded cell projection morphogenesis|
|regulation of cell morphogenesis|
|cell projection morphogenesis|
|actin cytoskeleton organization|
|regulation of neuron projection development|
|positive regulation of cell migration|
|positive regulation of multi-organism process|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|regulation of lymphocyte activation|
|cell part morphogenesis|
|regulation of anatomical structure size|
|regulation of protein serine/threonine kinase activity|
|positive regulation of cellular component biogenesis|
|regulation of response to biotic stimulus|
|positive regulation of cell motility|
|positive regulation of protein kinase activity|
|positive regulation of nervous system development|
|positive regulation of cellular component movement|
|regulation of cellular protein localization|
|regulation of cytoskeleton organization|
|positive regulation of cell development|
|positive regulation of MAPK cascade|
|positive regulation of locomotion|
|immune response-activating signal transduction|
|tissue morphogenesis|
|actin filament-based process|
|response to wounding|
|positive regulation of kinase activity|
|regulation of system process|
|immune response-regulating signaling pathway|
|protein-containing complex|
|cellular response to organonitrogen compound|
|regulation of leukocyte activation|
|positive regulation of response to external stimulus|
|cellular response to hormone stimulus|
|positive regulation of organelle organization|
|activation of immune response|
|regulation of cell activation|
|tube morphogenesis|
|regulation of neuron differentiation|
|positive regulation of transferase activity|
|cellular response to nitrogen compound|
|neuron projection development|
|regulation of growth|
|negative regulation of cell population proliferation|
|regulation of cell adhesion|
|regulation of plasma membrane bounded cell projection organization|
|chromatin organization|
|regulation of protein transport|
|regulation of cell projection organization|
|negative regulation of cell differentiation|
|enzyme linked receptor protein signaling pathway|
|cell morphogenesis|
|regulation of cellular response to stress|
|regulation of peptide transport|
|brain development|
|regulation of establishment of protein localization|
|regulation of MAPK cascade|
|regulation of defense response|
|cellular response to DNA damage stimulus|
|regulation of multi-organism process|
|head development|
|exocytosis|
|regulation of protein kinase activity|
|neuron development|
|regulation of neurogenesis|
|cellular component morphogenesis|
|tube development|
|regulation of cell migration|
|positive regulation of immune response|
|regulation of kinase activity|
|response to hormone|
|regulation of cell motility|
|regulation of cellular localization|
|positive regulation of cell population proliferation|
|apoptotic process|
|regulation of nervous system development|
|regulation of cell development|
|negative regulation of developmental process|
|regulation of cellular component biogenesis|
|cell migration|
|positive regulation of cell differentiation|
|protein phosphorylation|
|regulation of transferase activity|
|central nervous system development|
|regulation of locomotion|
|positive regulation of transport|
|regulation of cellular component movement|
|response to organonitrogen compound|
|secretion by cell|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|regulation of protein localization|
|export from cell|
|programmed cell death|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|regulation of anatomical structure morphogenesis|
|chromosome organization|
|localization of cell|
|cell motility|
|response to nitrogen compound|
|cell death|
|immune effector process|
|regulation of response to external stimulus|
|cytoskeleton organization|
|epithelium development|
|secretion|
|plasma membrane bounded cell projection organization|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|regulation of immune response|
|positive regulation of immune system process|
|response to abiotic stimulus|
|cell projection organization|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|phosphorylation|
|regulation of organelle organization|
|locomotion|
|positive regulation of developmental process|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|regulation of response to stress|
|ATP binding|
|generation of neurons|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|neurogenesis|
|cell development|
|positive regulation of signal transduction|
|regulation of immune system process|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|tissue development|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|regulation of transport|
|vesicle-mediated transport|
</modal>
\\

 === CRISPR Data ===
<button type='default' 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'>
No hits were found.
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:h:hgc6.3|HGC6.3]]|0.507|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 11751
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 4.95 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='PAK1 Expression in NALM6 Cells: 4.95'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>