MAP3K8 [The Human Chemical-Genetic Interaction Map Project]

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======= MAP3K8 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: MAP3K8
  * **<color #00a2e8>Official Name</color>**: mitogen-activated protein kinase kinase kinase 8
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=1326|1326]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P41279|P41279]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=MAP3K8&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20MAP3K8|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/191195|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene is an oncogene that encodes a member of the serine/threonine protein kinase family. The encoded protein localizes to the cytoplasm and can activate both the MAP kinase and JNK kinase pathways. This protein was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This protein was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. This gene may also utilize a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Required for lipopolysaccharide (LPS)-induced, TLR4- mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF- alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B- cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant. {ECO:0000269|PubMed:11342626, ECO:0000269|PubMed:12667451, ECO:0000269|PubMed:15169888, ECO:0000269|PubMed:16371247, ECO:0000269|PubMed:1833717, ECO:0000269|PubMed:19001140, ECO:0000269|PubMed:19754427, ECO:0000269|PubMed:19808894}.

<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'>
|MAP kinase kinase kinase activity|
|activation of MAPKK activity|
|T cell costimulation|
|lymphocyte costimulation|
|interleukin-1-mediated signaling pathway|
|stress-activated MAPK cascade|
|stress-activated protein kinase signaling cascade|
|cellular response to interleukin-1|
|response to interleukin-1|
|positive regulation of T cell activation|
|magnesium ion binding|
|positive regulation of leukocyte cell-cell adhesion|
|positive regulation of cell-cell adhesion|
|positive regulation of MAP kinase activity|
|regulation of leukocyte cell-cell adhesion|
|regulation of T cell activation|
|activation of protein kinase activity|
|positive regulation of protein serine/threonine kinase activity|
|regulation of MAP kinase activity|
|positive regulation of lymphocyte activation|
|protein serine/threonine kinase activity|
|MAPK cascade|
|signal transduction by protein phosphorylation|
|regulation of cell-cell adhesion|
|positive regulation of cell adhesion|
|positive regulation of leukocyte activation|
|positive regulation of cell activation|
|regulation of lymphocyte activation|
|regulation of protein serine/threonine kinase activity|
|positive regulation of protein kinase activity|
|positive regulation of MAPK cascade|
|positive regulation of kinase activity|
|regulation of leukocyte activation|
|regulation of cell activation|
|positive regulation of transferase activity|
|cytokine-mediated signaling pathway|
|regulation of cell adhesion|
|regulation of MAPK cascade|
|regulation of protein kinase activity|
|regulation of kinase activity|
|protein phosphorylation|
|regulation of transferase activity|
|cellular response to cytokine stimulus|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|positive regulation of phosphorylation|
|response to cytokine|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|positive regulation of immune system process|
|positive regulation of protein modification process|
|phosphorylation|
|cell cycle|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|ATP binding|
|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 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|
</modal>
\\

 === CRISPR Data ===
<button type='primary' 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'>
^Screen^Score^
|[[:results:exp6|Bortezomib 0.005μM R00 exp6]]|-1.98|
|[[:results:exp247|UM0130462 0.025 to 0.035μM day4 R05 exp247]]|-1.71|
</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: 1/739
^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|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 9525
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 0.13 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='MAP3K8 Expression in NALM6 Cells: 0.13'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>