======= MAPKAPK2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: MAPKAPK2
  * **<color #00a2e8>Official Name</color>**: MAPK activated protein kinase 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=9261|9261]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P49137|P49137]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=MAPKAPK2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20MAPKAPK2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/602006|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a member of the Ser/Thr protein kinase family. This kinase is regulated through direct phosphorylation by p38 MAP kinase. In conjunction with p38 MAP kinase, this kinase is known to be involved in many cellular processes including stress and inflammatory responses, nuclear export, gene expression regulation and cell proliferation. Heat shock protein HSP27 was shown to be one of the substrates of this kinase in vivo. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (PubMed:16278218). Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (PubMed:26616734). Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:11844797, ECO:0000269|PubMed:12456657, ECO:0000269|PubMed:12565831, ECO:0000269|PubMed:14499342, ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15629715, ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:16456544, ECO:0000269|PubMed:17481585, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:8093612, ECO:0000269|PubMed:8280084, ECO:0000269|PubMed:8774846}.

<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|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|calcium-dependent protein serine/threonine kinase activity|
|p38MAPK cascade|
|macropinocytosis|
|pinocytosis|
|3-UTR-mediated mRNA stabilization|
|positive regulation of tumor necrosis factor biosynthetic process|
|mitogen-activated protein kinase binding|
|calmodulin-dependent protein kinase activity|
|regulation of tumor necrosis factor biosynthetic process|
|leukotriene metabolic process|
|cellular response to vascular endothelial growth factor stimulus|
|mRNA stabilization|
|RNA stabilization|
|negative regulation of mRNA catabolic process|
|negative regulation of RNA catabolic process|
|vascular endothelial growth factor receptor signaling pathway|
|positive regulation of cytokine biosynthetic process|
|regulation of cellular response to heat|
|negative regulation of mRNA metabolic process|
|positive regulation of tumor necrosis factor production|
|positive regulation of tumor necrosis factor superfamily cytokine production|
|toll-like receptor signaling pathway|
|stress-activated MAPK cascade|
|regulation of cytokine biosynthetic process|
|icosanoid metabolic process|
|pattern recognition receptor signaling pathway|
|regulation of interleukin-6 production|
|stress-activated protein kinase signaling cascade|
|regulation of tumor necrosis factor production|
|regulation of tumor necrosis factor superfamily cytokine production|
|activation of MAPK activity|
|fatty acid derivative metabolic process|
|peptidyl-serine phosphorylation|
|regulation of mRNA stability|
|regulation of RNA stability|
|protein autophosphorylation|
|inner ear development|
|peptidyl-serine modification|
|regulation of mRNA catabolic process|
|calmodulin binding|
|ear development|
|innate immune response-activating signal transduction|
|protein kinase activity|
|negative regulation of cellular catabolic process|
|activation of innate immune response|
|positive regulation of MAP kinase activity|
|negative regulation of catabolic process|
|response to lipopolysaccharide|
|response to molecule of bacterial origin|
|activation of protein kinase activity|
|regulation of mRNA metabolic process|
|positive regulation of protein serine/threonine kinase activity|
|positive regulation of innate immune response|
|regulation of MAP kinase activity|
|positive regulation of response to biotic stimulus|
|protein serine/threonine kinase activity|
|MAPK cascade|
|signal transduction by protein phosphorylation|
|positive regulation of cytokine production|
|regulation of innate immune response|
|positive regulation of defense response|
|centrosome|
|inflammatory response|
|cellular response to growth factor stimulus|
|positive regulation of multi-organism process|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|regulation of protein serine/threonine kinase activity|
|regulation of response to biotic stimulus|
|posttranscriptional regulation of gene expression|
|response to growth factor|
|positive regulation of protein kinase activity|
|positive regulation of MAPK cascade|
|sensory organ development|
|endocytosis|
|immune response-activating signal transduction|
|positive regulation of kinase activity|
|immune response-regulating signaling pathway|
|positive regulation of response to external stimulus|
|activation of immune response|
|positive regulation of transferase activity|
|import into cell|
|response to bacterium|
|regulation of cytokine production|
|enzyme linked receptor protein signaling pathway|
|regulation of cellular response to stress|
|regulation of MAPK cascade|
|regulation of defense response|
|cellular response to DNA damage stimulus|
|regulation of multi-organism process|
|regulation of protein kinase activity|
|regulation of cellular catabolic process|
|response to lipid|
|positive regulation of immune response|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|carboxylic acid metabolic process|
|protein phosphorylation|
|regulation of transferase activity|
|regulation of catabolic process|
|oxoacid metabolic process|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|organic acid metabolic process|
|positive regulation of phosphorylation|
|regulation of response to external stimulus|
|response to cytokine|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|positive regulation of immune system process|
|regulation of immune response|
|positive regulation of protein modification process|
|phosphorylation|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|negative regulation of RNA metabolic process|
|defense response|
|positive regulation of catalytic activity|
|negative regulation of nucleobase-containing compound metabolic process|
|regulation of protein phosphorylation|
|regulation of response to stress|
|ATP binding|
|response to oxygen-containing compound|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of immune system process|
|positive regulation of signal transduction|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|small molecule 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|
|positive regulation of macromolecule biosynthetic process|
|vesicle-mediated transport|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic 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:exp15|Cycloheximide 0.2μM R00 exp15]]|-1.78|
|[[:results:exp504|MK2206 4μM R08 exp504]]|-1.77|
|[[:results:exp146|Quinacrine 2.5μM R03 exp146]]|-1.74|
|[[:results:exp423|Zebularine 20μM R07 exp423]]|-1.74|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:h:hgc6.3|HGC6.3]]|0.536|
</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>**: 16356
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.8 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='MAPKAPK2 Expression in NALM6 Cells: 6.8'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>