======= MAP3K5 =======
== Gene Information ==
* **Official Symbol**: MAP3K5
* **Official Name**: mitogen-activated protein kinase kinase kinase 5
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=4217|4217]]
* **UniProt**: [[https://www.uniprot.org/uniprot/Q99683|Q99683]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=MAP3K5&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20MAP3K5|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/602448|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. MAPKKK5 contains 1,374 amino acids with all 11 kinase subdomains. Northern blot analysis shows that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. The MAPKKK5 protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) during transient expression in COS and 293 cells; MAPKKK5 does not activate MAPK/ERK. [provided by RefSeq, Jul 2008].
* **UniProt Summary**: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1). {ECO:0000269|PubMed:10411906, ECO:0000269|PubMed:10688666, ECO:0000269|PubMed:10849426, ECO:0000269|PubMed:11029458, ECO:0000269|PubMed:11154276, ECO:0000269|PubMed:11689443, ECO:0000269|PubMed:11920685, ECO:0000269|PubMed:12697749, ECO:0000269|PubMed:14688258, ECO:0000269|PubMed:14749717, ECO:0000269|PubMed:15023544, ECO:0000269|PubMed:16129676, ECO:0000269|PubMed:17220297, ECO:0000269|PubMed:23102700, ECO:0000269|PubMed:8940179, ECO:0000269|PubMed:8974401, ECO:0000269|PubMed:9564042, ECO:0000269|PubMed:9774977}.
|Pkinase Tyr|
|Pkinase|
|protein kinase complex|
|IRE1-TRAF2-ASK1 complex|
|p38MAPK cascade|
|endothelial cell apoptotic process|
|positive regulation of striated muscle cell apoptotic process|
|positive regulation of cardiac muscle cell apoptotic process|
|intrinsic apoptotic signaling pathway in response to oxidative stress|
|cellular response to reactive nitrogen species|
|MAP kinase kinase kinase activity|
|cell death in response to oxidative stress|
|positive regulation of myoblast differentiation|
|positive regulation of p38MAPK cascade|
|epithelial cell apoptotic process|
|positive regulation of muscle cell apoptotic process|
|programmed necrotic cell death|
|necrotic cell death|
|positive regulation of vascular smooth muscle cell proliferation|
|intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress|
|regulation of cardiac muscle cell apoptotic process|
|activation of JUN kinase activity|
|regulation of striated muscle cell apoptotic process|
|regulation of p38MAPK cascade|
|cellular response to amino acid starvation|
|response to amino acid starvation|
|response to ischemia|
|regulation of vascular smooth muscle cell proliferation|
|regulation of myoblast differentiation|
|activation of MAPKK activity|
|regulation of muscle cell apoptotic process|
|cellular response to hydrogen peroxide|
|positive regulation of JUN kinase activity|
|JNK cascade|
|positive regulation of smooth muscle cell proliferation|
|protein phosphatase binding|
|regulation of JUN kinase activity|
|positive regulation of neuron death|
|stress-activated MAPK cascade|
|cellular response to antibiotic|
|response to hydrogen peroxide|
|cellular response to reactive oxygen species|
|positive regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|regulation of smooth muscle cell proliferation|
|positive regulation of JNK cascade|
|stress-activated protein kinase signaling cascade|
|intrinsic apoptotic signaling pathway|
|cellular response to starvation|
|positive regulation of cysteine-type endopeptidase activity|
|activation of MAPK activity|
|positive regulation of stress-activated MAPK cascade|
|positive regulation of stress-activated protein kinase signaling cascade|
|positive regulation of endopeptidase activity|
|regulation of JNK cascade|
|positive regulation of peptidase activity|
|response to starvation|
|response to reactive oxygen species|
|cellular response to toxic substance|
|regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|magnesium ion binding|
|regulation of stress-activated MAPK cascade|
|cellular response to nutrient levels|
|regulation of stress-activated protein kinase signaling cascade|
|protein kinase activity|
|cellular response to tumor necrosis factor|
|cellular response to oxidative stress|
|regulation of cysteine-type endopeptidase activity|
|protein domain specific binding|
|response to endoplasmic reticulum stress|
|positive regulation of MAP kinase activity|
|response to tumor necrosis factor|
|cellular response to extracellular stimulus|
|apoptotic signaling pathway|
|response to antibiotic|
|regulation of neuron death|
|activation of protein kinase activity|
|cellular response to external stimulus|
|positive regulation of protein serine/threonine kinase activity|
|regulation of MAP kinase activity|
|positive regulation of proteolysis|
|protein serine/threonine kinase activity|
|MAPK cascade|
|response to oxidative stress|
|signal transduction by protein phosphorylation|
|external side of plasma membrane|
|cellular response to drug|
|regulation of endopeptidase activity|
|regulation of peptidase activity|
|protein kinase binding|
|wound healing|
|response to nutrient levels|
|response to toxic substance|
|regulation of protein serine/threonine kinase activity|
|response to extracellular stimulus|
|response to inorganic substance|
|positive regulation of protein kinase activity|
|positive regulation of MAPK cascade|
|response to wounding|
|positive regulation of kinase activity|
|protein-containing complex|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|positive regulation of transferase activity|
|cellular response to nitrogen compound|
|positive regulation of cell death|
|viral process|
|regulation of proteolysis|
|regulation of cellular response to stress|
|regulation of MAPK cascade|
|innate immune response|
|positive regulation of hydrolase activity|
|symbiotic process|
|regulation of protein kinase activity|
|interspecies interaction between organisms|
|regulation of kinase activity|
|protein homodimerization activity|
|positive regulation of cell population proliferation|
|apoptotic process|
|defense response to other organism|
|positive regulation of cell differentiation|
|protein phosphorylation|
|regulation of transferase activity|
|cellular response to cytokine stimulus|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|response to drug|
|programmed cell death|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|identical protein binding|
|response to nitrogen compound|
|cell death|
|response to cytokine|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|positive regulation of protein modification process|
|regulation of hydrolase activity|
|phosphorylation|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|defense response|
|positive regulation of developmental process|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|regulation of response to stress|
|ATP binding|
|regulation of apoptotic process|
|positive regulation of transcription, DNA-templated|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|positive regulation of signal transduction|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|positive regulation of RNA metabolic process|
|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|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic process|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp417|Tubastatin-A 2.5μM R07 exp417]]|-2.1|
|[[:results:exp141|Nifurtimox 1μM R03 exp141]]|-1.9|
|[[:results:exp506|Momordin-Ic 10μM R08 exp506]]|-1.9|
|[[:results:exp510|Nicotine 3000μM R08 exp510]]|-1.8|
|[[:results:exp90|WYE-354 6μM R02 exp90]]|1.74|
|[[:results:exp290|LLY-283 2.6μM R06 exp290]]|1.9|
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|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|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 9224
* **Expression level (log2 read counts)**: 3.78
{{:chemogenomics:nalm6 dist.png?nolink |}}