======= MAPK1 =======
== Gene Information ==
* **Official Symbol**: MAPK1
* **Official Name**: mitogen-activated protein kinase 1
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5594|5594]]
* **UniProt**: [[https://www.uniprot.org/uniprot/P28482|P28482]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=MAPK1&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20MAPK1|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/176948|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: This gene encodes a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. One study also suggests that this protein acts as a transcriptional repressor independent of its kinase activity. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene. [provided by RefSeq, Jan 2014].
* **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, DCC, 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. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity). {ECO:0000250|UniProtKB:P63086, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:10637505, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12792650, ECO:0000269|PubMed:12794087, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15184391, ECO:0000269|PubMed:15241487, ECO:0000269|PubMed:15616583, ECO:0000269|PubMed:15664191, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:19879846, ECO:0000269|PubMed:22033920, ECO:0000269|PubMed:7588608, ECO:0000269|PubMed:8622688, ECO:0000269|PubMed:9480836, ECO:0000269|PubMed:9596579, ECO:0000269|PubMed:9649500, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:15526160, ECO:0000303|PubMed:16393692, ECO:0000303|PubMed:19565474, ECO:0000303|PubMed:21779493}.
|Pkinase Tyr|
|Pkinase|
|cytosine metabolic process|
|diadenosine tetraphosphate metabolic process|
|diadenosine tetraphosphate biosynthetic process|
|diadenosine polyphosphate biosynthetic process|
|regulation of Golgi inheritance|
|caveolin-mediated endocytosis|
|trachea formation|
|Bergmann glial cell differentiation|
|diadenosine polyphosphate metabolic process|
|cardiac neural crest cell differentiation involved in heart development|
|cardiac neural crest cell development involved in heart development|
|cellular response to granulocyte macrophage colony-stimulating factor stimulus|
|response to granulocyte macrophage colony-stimulating factor|
|outer ear morphogenesis|
|trachea morphogenesis|
|mammary gland epithelial cell proliferation|
|MAP kinase activity|
|regulation of Golgi organization|
|regulation of early endosome to late endosome transport|
|pseudopodium|
|MAP kinase kinase activity|
|positive regulation of telomere capping|
|mitogen-activated protein kinase kinase kinase binding|
|RNA polymerase II CTD heptapeptide repeat kinase activity|
|trachea development|
|labyrinthine layer blood vessel development|
|pyrimidine nucleobase metabolic process|
|thyroid gland development|
|decidualization|
|regulation of cytoplasmic transport|
|positive regulation of cardiac muscle cell proliferation|
|regulation of telomere capping|
|ERK1 and ERK2 cascade|
|positive regulation of peptidyl-threonine phosphorylation|
|placenta blood vessel development|
|dendrite cytoplasm|
|positive regulation of cardiac muscle tissue growth|
|positive regulation of telomere maintenance via telomerase|
|animal organ formation|
|lipopolysaccharide-mediated signaling pathway|
|maternal placenta development|
|positive regulation of telomerase activity|
|positive regulation of protein import into nucleus|
|positive regulation of telomere maintenance via telomere lengthening|
|positive regulation of heart growth|
|cellular response to cadmium ion|
|positive regulation of protein import|
|regulation of cardiac muscle cell proliferation|
|phosphotyrosine residue binding|
|nucleobase metabolic process|
|lung morphogenesis|
|cellular response to amino acid starvation|
|regulation of peptidyl-threonine phosphorylation|
|positive regulation of cardiac muscle tissue development|
|response to exogenous dsRNA|
|thymus development|
|response to amino acid starvation|
|labyrinthine layer development|
|long-term synaptic potentiation|
|response to epidermal growth factor|
|positive regulation of organ growth|
|face development|
|response to nicotine|
|phosphatase binding|
|positive regulation of telomere maintenance|
|regulation of telomerase activity|
|response to dsRNA|
|astrocyte differentiation|
|activation of MAPKK activity|
|regulation of telomere maintenance via telomerase|
|regulation of protein import into nucleus|
|regulation of protein import|
|regulation of cardiac muscle tissue growth|
|mammary gland epithelium development|
|regulation of telomere maintenance via telomere lengthening|
|positive regulation of nucleocytoplasmic transport|
|response to cadmium ion|
|regulation of heart growth|
|maternal process involved in female pregnancy|
|positive regulation of DNA biosynthetic process|
|positive regulation of muscle organ development|
|positive regulation of striated muscle tissue development|
|positive regulation of muscle tissue development|
|ERBB signaling pathway|
|positive regulation of protein localization to nucleus|
|caveola|
|sensory perception of pain|
|response to estrogen|
|mitotic spindle|
|regulation of cardiac muscle tissue development|
|regulation of cellular response to heat|
|neural crest cell development|
|fibroblast growth factor receptor signaling pathway|
|kinase activity|
|regulation of telomere maintenance|
|peptidyl-threonine phosphorylation|
|stem cell development|
|mesenchymal cell development|
|cellular response to dopamine|
|embryonic placenta development|
|response to dopamine|
|epithelial cell proliferation|
|neural crest cell differentiation|
|peptidyl-threonine modification|
|azurophil granule lumen|
|regulation of cellular pH|
|regulation of organ growth|
|regulation of pH|
|cellular response to catecholamine stimulus|
|cellular response to monoamine stimulus|
|double-stranded DNA binding|
|stress-activated MAPK cascade|
|response to catecholamine|
|pyrimidine-containing compound metabolic process|
|regulation of nucleocytoplasmic transport|
|response to monoamine|
|cellular monovalent inorganic cation homeostasis|
|cellular response to fibroblast growth factor stimulus|
|regulation of DNA biosynthetic process|
|cardiocyte differentiation|
|response to fibroblast growth factor|
|regulation of protein localization to nucleus|
|ear morphogenesis|
|regulation of phosphatidylinositol 3-kinase signaling|
|endocrine system development|
|ficolin-1-rich granule lumen|
|positive regulation of translation|
|late endosome|
|mammary gland development|
|B cell receptor signaling pathway|
|cellular response to ammonium ion|
|cellular response to reactive oxygen species|
|regulation of striated muscle tissue development|
|perikaryon|
|regulation of muscle tissue development|
|Fc-gamma receptor signaling pathway involved in phagocytosis|
|regulation of muscle organ development|
|immune response-regulating cell surface receptor signaling pathway involved in phagocytosis|
|platelet activation|
|Fc receptor mediated stimulatory signaling pathway|
|Fc-gamma receptor signaling pathway|
|monovalent inorganic cation homeostasis|
|stress-activated protein kinase signaling cascade|
|cellular response to starvation|
|positive regulation of cellular amide metabolic process|
|positive regulation of synaptic transmission|
|placenta development|
|positive regulation of intracellular protein transport|
|activation of MAPK activity|
|mesenchymal cell differentiation|
|microtubule organizing center|
|stem cell differentiation|
|lung development|
|glial cell differentiation|
|positive regulation of developmental growth|
|respiratory tube development|
|Fc-epsilon receptor signaling pathway|
|positive regulation of chromosome organization|
|peptidyl-serine phosphorylation|
|T cell receptor signaling pathway|
|female pregnancy|
|response to ammonium ion|
|cellular response to lipopolysaccharide|
|regulation of synaptic plasticity|
|regulation of ossification|
|cellular response to metal ion|
|cellular response to molecule of bacterial origin|
|response to starvation|
|positive regulation of DNA metabolic process|
|response to reactive oxygen species|
|respiratory system development|
|peptidyl-serine modification|
|positive regulation of intracellular transport|
|multi-multicellular organism process|
|gliogenesis|
|cellular response to biotic stimulus|
|cellular response to inorganic substance|
|mesenchyme development|
|ear development|
|regulation of intracellular protein transport|
|regulation of stress-activated MAPK cascade|
|cellular response to nutrient levels|
|regulation of stress-activated protein kinase signaling cascade|
|cellular response to tumor necrosis factor|
|cellular response to oxidative stress|
|Fc receptor signaling pathway|
|nucleotide biosynthetic process|
|nucleoside phosphate biosynthetic process|
|postsynaptic density|
|sensory organ morphogenesis|
|early endosome|
|learning or memory|
|positive regulation of growth|
|axon guidance|
|positive regulation of MAP kinase activity|
|neuron projection guidance|
|response to tumor necrosis factor|
|cellular response to extracellular stimulus|
|aging|
|regulation of protein stability|
|embryonic organ morphogenesis|
|blood coagulation|
|antigen receptor-mediated signaling pathway|
|coagulation|
|axon|
|hemostasis|
|cognition|
|response to lipopolysaccharide|
|positive regulation of cellular protein localization|
|response to molecule of bacterial origin|
|activation of protein kinase activity|
|regulation of developmental growth|
|phagocytosis|
|transcription factor binding|
|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|
|protein serine/threonine kinase activity|
|cytoskeleton|
|response to metal ion|
|axonogenesis|
|MAPK cascade|
|in utero embryonic development|
|response to oxidative stress|
|signal transduction by protein phosphorylation|
|regulation of cellular amide metabolic process|
|cellular response to drug|
|axon development|
|gland development|
|focal adhesion|
|anterograde trans-synaptic signaling|
|chemical synaptic transmission|
|positive regulation of protein transport|
|reproductive structure development|
|regulation of DNA-binding transcription factor activity|
|reproductive system development|
|cell morphogenesis involved in neuron differentiation|
|embryonic organ development|
|trans-synaptic signaling|
|modulation of chemical synaptic transmission|
|regulation of trans-synaptic signaling|
|nucleotide metabolic process|
|immune response-activating cell surface receptor signaling pathway|
|nucleoside phosphate metabolic process|
|positive regulation of establishment of protein localization|
|synaptic signaling|
|wound healing|
|neuron projection morphogenesis|
|immune response-regulating cell surface receptor signaling pathway|
|plasma membrane bounded cell projection morphogenesis|
|blood vessel development|
|neutrophil degranulation|
|cell projection morphogenesis|
|neutrophil activation involved in immune response|
|regulation of body fluid levels|
|response to nutrient levels|
|neutrophil mediated immunity|
|cellular response to growth factor stimulus|
|positive regulation of cell migration|
|neutrophil activation|
|granulocyte activation|
|response to toxic substance|
|vasculature development|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|leukocyte degranulation|
|cell part morphogenesis|
|regulation of protein serine/threonine kinase activity|
|myeloid leukocyte mediated immunity|
|cardiovascular system development|
|cellular response to lipid|
|positive regulation of cell motility|
|myeloid cell activation involved in immune response|
|posttranscriptional regulation of gene expression|
|heart development|
|response to extracellular stimulus|
|response to growth factor|
|positive regulation of protein kinase activity|
|response to inorganic substance|
|organophosphate biosynthetic process|
|positive regulation of cellular component movement|
|regulation of cellular protein localization|
|regulation of cytoskeleton organization|
|nucleobase-containing small molecule metabolic process|
|cellular response to organic cyclic compound|
|positive regulation of MAPK cascade|
|sensory organ development|
|chemotaxis|
|regulation of vesicle-mediated transport|
|positive regulation of locomotion|
|taxis|
|cell population proliferation|
|endocytosis|
|cell morphogenesis involved in differentiation|
|immune response-activating signal transduction|
|embryonic morphogenesis|
|response to wounding|
|behavior|
|positive regulation of kinase activity|
|myeloid leukocyte activation|
|immune response-regulating signaling pathway|
|protein-containing complex|
|cellular response to organonitrogen compound|
|hematopoietic or lymphoid organ development|
|positive regulation of organelle organization|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|activation of immune response|
|cellular cation homeostasis|
|chordate embryonic development|
|cellular ion homeostasis|
|immune system development|
|embryo development ending in birth or egg hatching|
|positive regulation of transferase activity|
|cellular response to nitrogen compound|
|neuron projection development|
|developmental process involved in reproduction|
|regulation of growth|
|import into cell|
|response to bacterium|
|viral process|
|regulated exocytosis|
|regulation of protein transport|
|cation homeostasis|
|negative regulation of cell differentiation|
|enzyme linked receptor protein signaling pathway|
|inorganic ion homeostasis|
|cell morphogenesis|
|regulation of cellular response to stress|
|regulation of peptide transport|
|cellular chemical homeostasis|
|regulation of establishment of protein localization|
|regulation of MAPK cascade|
|leukocyte mediated immunity|
|cellular response to DNA damage stimulus|
|head development|
|symbiotic process|
|ion homeostasis|
|exocytosis|
|regulation of protein kinase activity|
|neuron development|
|interspecies interaction between organisms|
|cellular component morphogenesis|
|multicellular organismal reproductive 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|
|organophosphate metabolic process|
|anatomical structure formation involved in morphogenesis|
|cellular homeostasis|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|regulation of cellular localization|
|response to organic cyclic compound|
|apoptotic process|
|leukocyte activation|
|negative regulation of developmental process|
|animal organ morphogenesis|
|sensory perception|
|protein phosphorylation|
|embryo development|
|regulation of transferase activity|
|central nervous system development|
|regulation of locomotion|
|Golgi apparatus|
|positive regulation of transport|
|multi-organism reproductive process|
|regulation of cellular component movement|
|response to organonitrogen compound|
|secretion by cell|
|cellular response to cytokine stimulus|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|response to drug|
|regulation of protein localization|
|export from cell|
|programmed cell death|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|identical protein binding|
|cell activation|
|response to nitrogen compound|
|immune effector process|
|cell death|
|nucleobase-containing compound biosynthetic process|
|response to cytokine|
|chemical homeostasis|
|epithelium development|
|cell-cell signaling|
|plasma membrane bounded cell projection organization|
|secretion|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|positive regulation of immune system process|
|regulation of immune response|
|cell projection organization|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|positive regulation of cellular component organization|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|mitochondrion|
|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|
|positive regulation of developmental process|
|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|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|neurogenesis|
|cellular nitrogen compound biosynthetic process|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|homeostatic process|
|cell development|
|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 RNA metabolic process|
|positive regulation of multicellular organismal process|
|small molecule metabolic 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|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|extracellular region|
|vesicle-mediated transport|
|system process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic process|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp365|I-BRD9 4μM R07 exp365]]|-1.94|
|[[:results:exp22|MLN-4924 2μM R00 exp22]]|1.77|
|[[:results:exp82|Torin1 0.08μM R02 exp82]]|1.86|
|[[:results:exp147|Resveratrol 16μM R03 exp147]]|1.98|
|[[:results:exp148|SB202190 10μM R03 exp148]]|2.49|
|[[:results:exp514|Phorbol-12-myristate-13-acetate 0.57μM R08 exp514]]|4.42|
^Gene^Correlation^
|[[:human genes:n:nras|NRAS]]|0.551|
|[[:human genes:r:raf1|RAF1]]|0.461|
|[[:human genes:s:shoc2|SHOC2]]|0.445|
Global Fraction of Cell Lines Where Essential: 16/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|1/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|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|9/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 3592
* **Expression level (log2 read counts)**: 7.49
{{:chemogenomics:nalm6 dist.png?nolink |}}