======= MAPK3 =======
== Gene Information ==
* **Official Symbol**: MAPK3
* **Official Name**: mitogen-activated protein kinase 3
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5595|5595]]
* **UniProt**: [[https://www.uniprot.org/uniprot/P27361|P27361]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=MAPK3&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20MAPK3|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/601795|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described. [provided by RefSeq, Jul 2008].
* **UniProt Summary**: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. {ECO:0000269|PubMed:10393181, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:8325880, ECO:0000269|PubMed:9155018, ECO:0000269|PubMed:9480836}.
|Pkinase Tyr|
|Pkinase|
|negative regulation of apolipoprotein binding|
|regulation of apolipoprotein binding|
|regulation of Golgi inheritance|
|caveolin-mediated endocytosis|
|positive regulation of xenophagy|
|regulation of xenophagy|
|trachea formation|
|positive regulation of metallopeptidase activity|
|Bergmann glial cell differentiation|
|positive regulation of histone phosphorylation|
|cardiac neural crest cell development involved in heart development|
|DNA damage induced protein phosphorylation|
|positive regulation of cytokine secretion involved in immune response|
|cardiac neural crest cell differentiation involved in heart development|
|outer ear morphogenesis|
|trachea morphogenesis|
|regulation of histone phosphorylation|
|regulation of metallopeptidase activity|
|MAP kinase activity|
|positive regulation of macrophage chemotaxis|
|regulation of Golgi organization|
|regulation of cytokine secretion involved in immune response|
|positive regulation of telomere capping|
|regulation of early endosome to late endosome transport|
|pseudopodium|
|MAP kinase kinase activity|
|trachea development|
|positive regulation of macrophage migration|
|positive regulation of cyclase activity|
|thyroid gland development|
|regulation of cytoplasmic transport|
|decidualization|
|regulation of telomere capping|
|regulation of macrophage chemotaxis|
|ERK1 and ERK2 cascade|
|positive regulation of histone acetylation|
|peptidyl-tyrosine autophosphorylation|
|positive regulation of peptidyl-lysine acetylation|
|animal organ formation|
|lipopolysaccharide-mediated signaling pathway|
|positive regulation of telomere maintenance via telomerase|
|maternal placenta development|
|transcription initiation from RNA polymerase I promoter|
|positive regulation of telomerase activity|
|regulation of macrophage migration|
|positive regulation of telomere maintenance via telomere lengthening|
|cellular response to cadmium ion|
|transcription by RNA polymerase I|
|phosphotyrosine residue binding|
|positive regulation of protein acetylation|
|regulation of granulocyte chemotaxis|
|lung morphogenesis|
|cellular response to amino acid starvation|
|regulation of cyclase activity|
|response to exogenous dsRNA|
|thymus development|
|regulation of mononuclear cell migration|
|response to amino acid starvation|
|response to epidermal growth factor|
|face development|
|phosphatase binding|
|positive regulation of telomere maintenance|
|regulation of telomerase activity|
|response to dsRNA|
|astrocyte differentiation|
|activation of MAPKK activity|
|positive regulation of cytokine production involved in immune response|
|regulation of telomere maintenance via telomerase|
|regulation of histone acetylation|
|arachidonic acid metabolic process|
|scaffold protein binding|
|regulation of telomere maintenance via telomere lengthening|
|regulation of peptidyl-lysine acetylation|
|response to cadmium ion|
|maternal process involved in female pregnancy|
|positive regulation of DNA biosynthetic process|
|positive regulation of macroautophagy|
|regulation of protein acetylation|
|sensory perception of pain|
|caveola|
|neural crest cell development|
|cellular response to mechanical stimulus|
|regulation of cellular response to heat|
|fibroblast growth factor receptor signaling pathway|
|regulation of telomere maintenance|
|mesenchymal cell development|
|stem cell development|
|regulation of cytokine production involved in immune response|
|cellular response to dopamine|
|response to dopamine|
|positive regulation of leukocyte chemotaxis|
|neural crest cell differentiation|
|BMP signaling pathway|
|regulation of cellular pH|
|positive regulation of histone modification|
|interleukin-1-mediated signaling pathway|
|positive regulation of production of molecular mediator of immune response|
|regulation of pH|
|cellular response to monoamine stimulus|
|cellular response to catecholamine stimulus|
|negative regulation of protein binding|
|positive regulation of chromatin organization|
|cellular response to BMP stimulus|
|stress-activated MAPK cascade|
|response to BMP|
|response to monoamine|
|response to catecholamine|
|unsaturated fatty acid metabolic process|
|cellular response to fibroblast growth factor stimulus|
|cellular monovalent inorganic cation homeostasis|
|icosanoid metabolic process|
|regulation of DNA biosynthetic process|
|regulation of leukocyte chemotaxis|
|response to fibroblast growth factor|
|cardiocyte differentiation|
|long-chain fatty acid metabolic process|
|ear morphogenesis|
|regulation of phosphatidylinositol 3-kinase signaling|
|positive regulation of autophagy|
|endocrine system development|
|positive regulation of translation|
|late endosome|
|positive regulation of leukocyte migration|
|cellular response to ammonium ion|
|cellular response to reactive oxygen species|
|immune response-regulating cell surface receptor signaling pathway involved in phagocytosis|
|positive regulation of chemotaxis|
|Fc-gamma receptor signaling pathway involved in phagocytosis|
|platelet activation|
|Fc receptor mediated stimulatory signaling pathway|
|positive regulation of cytokine secretion|
|Fc-gamma receptor signaling pathway|
|monovalent inorganic cation homeostasis|
|regulation of production of molecular mediator of immune response|
|stress-activated protein kinase signaling cascade|
|peptidyl-tyrosine phosphorylation|
|regulation of histone modification|
|peptidyl-tyrosine modification|
|cellular response to starvation|
|positive regulation of cellular amide metabolic process|
|placenta development|
|activation of MAPK activity|
|mesenchymal cell differentiation|
|stem cell differentiation|
|fatty acid derivative metabolic process|
|lung development|
|negative regulation of binding|
|glial cell differentiation|
|cartilage development|
|respiratory tube development|
|regulation of macroautophagy|
|Fc-epsilon receptor signaling pathway|
|cellular response to interleukin-1|
|positive regulation of chromosome organization|
|peptidyl-serine phosphorylation|
|nuclear envelope|
|female pregnancy|
|cellular response to lipopolysaccharide|
|response to ammonium ion|
|regulation of chromatin organization|
|regulation of ossification|
|cellular response to molecule of bacterial origin|
|cellular response to metal ion|
|positive regulation of peptidase activity|
|protein autophosphorylation|
|response to starvation|
|positive regulation of DNA metabolic process|
|response to reactive oxygen species|
|regulation of leukocyte migration|
|respiratory system development|
|response to interleukin-1|
|transmembrane receptor protein serine/threonine kinase signaling pathway|
|peptidyl-serine modification|
|regulation of cytokine secretion|
|multi-multicellular organism process|
|positive regulation of ERK1 and ERK2 cascade|
|response to mechanical stimulus|
|regulation of chemotaxis|
|gliogenesis|
|cellular response to biotic stimulus|
|DNA-templated transcription, initiation|
|positive regulation of immune effector process|
|regulation of protein binding|
|cellular response to inorganic substance|
|ear development|
|mesenchyme development|
|connective tissue development|
|cellular response to nutrient levels|
|regulation of stress-activated MAPK cascade|
|regulation of stress-activated protein kinase signaling cascade|
|cellular response to oxidative stress|
|cellular response to tumor necrosis factor|
|Fc receptor signaling pathway|
|early endosome|
|sensory organ morphogenesis|
|axon guidance|
|neuron projection guidance|
|positive regulation of MAP kinase activity|
|response to tumor necrosis factor|
|cellular response to extracellular stimulus|
|positive regulation of protein secretion|
|aging|
|embryonic organ morphogenesis|
|positive regulation of peptide secretion|
|blood coagulation|
|regulation of ERK1 and ERK2 cascade|
|coagulation|
|hemostasis|
|response to lipopolysaccharide|
|cellular response to abiotic stimulus|
|cellular response to environmental stimulus|
|fatty acid metabolic process|
|response to molecule of bacterial origin|
|activation of protein kinase activity|
|phagocytosis|
|regulation of autophagy|
|cellular response to external stimulus|
|positive regulation of protein serine/threonine kinase activity|
|regulation of MAP kinase activity|
|regulation of chromosome organization|
|regulation of intracellular transport|
|regulation of translation|
|regulation of DNA metabolic process|
|positive regulation of proteolysis|
|positive regulation of response to biotic stimulus|
|positive regulation of cellular catabolic process|
|cytoskeleton|
|response to metal ion|
|axonogenesis|
|MAPK cascade|
|regulation of binding|
|response to oxidative stress|
|signal transduction by protein phosphorylation|
|cellular response to drug|
|regulation of cellular amide metabolic process|
|positive regulation of secretion by cell|
|axon development|
|gland development|
|focal adhesion|
|reproductive structure development|
|positive regulation of protein transport|
|regulation of DNA-binding transcription factor activity|
|reproductive system development|
|positive regulation of catabolic process|
|cell morphogenesis involved in neuron differentiation|
|embryonic organ development|
|positive regulation of secretion|
|regulation of peptidase activity|
|positive regulation of cytokine production|
|immune response-activating cell surface receptor signaling pathway|
|positive regulation of establishment of protein localization|
|regulation of protein secretion|
|regulation of immune effector process|
|positive regulation of defense response|
|wound healing|
|neuron projection morphogenesis|
|immune response-regulating cell surface receptor signaling pathway|
|plasma membrane bounded cell projection morphogenesis|
|cell projection morphogenesis|
|regulation of peptide secretion|
|skeletal system development|
|regulation of body fluid levels|
|response to nutrient levels|
|positive regulation of cell migration|
|cellular response to growth factor stimulus|
|response to toxic substance|
|positive regulation of multi-organism process|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|cell part morphogenesis|
|regulation of protein serine/threonine kinase activity|
|cellular response to lipid|
|regulation of response to biotic stimulus|
|positive regulation of cell motility|
|posttranscriptional regulation of gene expression|
|heart development|
|monocarboxylic acid metabolic process|
|response to growth factor|
|response to extracellular stimulus|
|response to inorganic substance|
|positive regulation of protein kinase activity|
|positive regulation of cellular component movement|
|regulation of cytoskeleton organization|
|cellular response to organic cyclic compound|
|positive regulation of MAPK cascade|
|sensory organ development|
|chemotaxis|
|regulation of vesicle-mediated transport|
|taxis|
|positive regulation of locomotion|
|endocytosis|
|cell morphogenesis involved in differentiation|
|immune response-activating signal transduction|
|embryonic morphogenesis|
|response to wounding|
|positive regulation of kinase activity|
|immune response-regulating signaling pathway|
|protein-containing complex|
|cellular response to organonitrogen compound|
|positive regulation of response to external stimulus|
|hematopoietic or lymphoid organ development|
|positive regulation of organelle organization|
|activation of immune response|
|cellular cation homeostasis|
|transcription, DNA-templated|
|nucleic acid-templated transcription|
|cellular ion homeostasis|
|immune system development|
|RNA biosynthetic process|
|positive regulation of transferase activity|
|cellular response to nitrogen compound|
|neuron projection development|
|developmental process involved in reproduction|
|cytokine-mediated signaling pathway|
|import into cell|
|response to bacterium|
|regulation of cytokine production|
|viral process|
|cation homeostasis|
|regulation of protein transport|
|enzyme linked receptor protein signaling pathway|
|inorganic ion homeostasis|
|cell morphogenesis|
|regulation of proteolysis|
|regulation of cellular response to stress|
|regulation of peptide transport|
|cellular chemical homeostasis|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|regulation of MAPK cascade|
|regulation of defense response|
|positive regulation of hydrolase activity|
|cellular response to DNA damage stimulus|
|regulation of multi-organism process|
|head development|
|symbiotic process|
|ion homeostasis|
|regulation of protein kinase activity|
|regulation of secretion|
|neuron development|
|interspecies interaction between organisms|
|cellular component morphogenesis|
|multicellular organismal reproductive process|
|regulation of cellular catabolic process|
|multicellular organism reproduction|
|tube development|
|regulation of cell migration|
|response to lipid|
|positive regulation of immune response|
|circulatory system development|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|anatomical structure formation involved in morphogenesis|
|cellular homeostasis|
|carboxylic acid metabolic process|
|regulation of cell motility|
|regulation of cellular localization|
|response to organic cyclic compound|
|apoptotic process|
|animal organ morphogenesis|
|cellular lipid metabolic process|
|sensory perception|
|protein phosphorylation|
|regulation of transferase activity|
|embryo development|
|central nervous system development|
|regulation of locomotion|
|Golgi apparatus|
|positive regulation of transport|
|regulation of cellular component movement|
|regulation of catabolic process|
|multi-organism reproductive process|
|response to organonitrogen compound|
|oxoacid metabolic process|
|cellular response to cytokine stimulus|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|response to drug|
|organic acid metabolic process|
|regulation of protein localization|
|programmed cell death|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|identical protein binding|
|cell activation|
|response to nitrogen compound|
|cell death|
|immune effector process|
|regulation of response to external stimulus|
|nucleobase-containing compound biosynthetic process|
|response to cytokine|
|chemical homeostasis|
|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|
|response to abiotic stimulus|
|cell projection organization|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|positive regulation of cellular component organization|
|lipid metabolic process|
|positive regulation of transcription by RNA polymerase II|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|mitochondrion|
|regulation of hydrolase activity|
|phosphorylation|
|regulation of organelle organization|
|response to other organism|
|organic cyclic compound biosynthetic process|
|response to external biotic stimulus|
|locomotion|
|response to biotic stimulus|
|cell cycle|
|nervous system process|
|reproductive process|
|reproduction|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|regulation of response to stress|
|ATP binding|
|generation of neurons|
|positive regulation of transcription, DNA-templated|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|neurogenesis|
|cellular nitrogen compound biosynthetic process|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|homeostatic process|
|cell development|
|positive regulation of signal transduction|
|regulation of immune system process|
|RNA metabolic process|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|cellular macromolecule biosynthetic process|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|small molecule metabolic process|
|tissue development|
|macromolecule biosynthetic 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|
|protein-containing complex subunit organization|
|regulation of transport|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|vesicle-mediated transport|
|system process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|gene expression|
|positive regulation of biosynthetic process|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp42|BI-6727 0.001μM R01 exp42]]|1.86|
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 1/726
^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|1/33|
|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|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 4361
* **Expression level (log2 read counts)**: 4.42
{{:chemogenomics:nalm6 dist.png?nolink |}}