MAPKAPK3 [The Human Chemical-Genetic Interaction Map Project]

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======= MAPKAPK3 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: MAPKAPK3
  * **<color #00a2e8>Official Name</color>**: MAPK activated protein kinase 3
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=7867|7867]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q16644|Q16644]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=MAPKAPK3&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20MAPKAPK3|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/602130|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a member of the Ser/Thr protein kinase family. This kinase functions as a mitogen-activated protein kinase (MAP kinase)- activated protein kinase. MAP kinases are also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This kinase was shown to be activated by growth inducers and stress stimulation of cells. In vitro studies demonstrated that ERK, p38 MAP kinase and Jun N-terminal kinase were all able to phosphorylate and activate this kinase, which suggested the role of this kinase as an integrative element of signaling in both mitogen and stress responses. This kinase was reported to interact with, phosphorylate and repress the activity of E47, which is a basic helix-loop-helix transcription factor known to be involved in the regulation of tissue-specific gene expression and cell differentiation. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling 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. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair 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, such as TTP/ZFP36, leading to regulate 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 transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:15563468, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20599781, ECO:0000269|PubMed:8626550, 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'>
|Kdo|
|Pkinase|
|Pkinase Tyr|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|calcium-dependent protein serine/threonine kinase activity|
|macropinocytosis|
|pinocytosis|
|MAP kinase kinase activity|
|mitogen-activated protein kinase binding|
|calmodulin-dependent protein kinase activity|
|vascular endothelial growth factor receptor signaling pathway|
|toll-like receptor signaling pathway|
|pattern recognition receptor signaling pathway|
|activation of MAPK activity|
|peptidyl-serine phosphorylation|
|protein autophosphorylation|
|peptidyl-serine modification|
|calmodulin binding|
|innate immune response-activating signal transduction|
|activation of innate immune response|
|positive regulation of MAP kinase activity|
|response to lipopolysaccharide|
|response to molecule of bacterial origin|
|activation of protein kinase activity|
|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|
|regulation of innate immune response|
|positive regulation of defense response|
|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|
|positive regulation of protein kinase activity|
|positive regulation of MAPK cascade|
|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|
|enzyme linked receptor protein signaling pathway|
|regulation of MAPK cascade|
|regulation of defense response|
|regulation of multi-organism process|
|regulation of protein kinase activity|
|response to lipid|
|positive regulation of immune response|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|protein phosphorylation|
|regulation of transferase activity|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|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|
|regulation of immune response|
|positive regulation of immune system process|
|positive regulation of protein modification process|
|phosphorylation|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|positive regulation of catalytic activity|
|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|
|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|
|vesicle-mediated transport|
</modal>
\\

 === CRISPR Data ===
<button type='default' 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'>
No hits were found.
</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: 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>**: 18361
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.39 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='MAPKAPK3 Expression in NALM6 Cells: 5.39'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>