======= MAP2K4 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: MAP2K4
  * **<color #00a2e8>Official Name</color>**: mitogen-activated protein kinase kinase 4
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=6416|6416]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P45985|P45985]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=MAP2K4&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20MAP2K4|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/601335|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a member of the mitogen-activated protein kinase (MAPK) family. Members of this family 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. They form a three-tiered signaling module composed of MAPKKKs, MAPKKs, and MAPKs. This protein is phosphorylated at serine and threonine residues by MAPKKKs and subsequently phosphorylates downstream MAPK targets at threonine and tyrosine residues. A similar protein in mouse has been reported to play a role in liver organogenesis. A pseudogene of this gene is located on the long arm of chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14. {ECO:0000269|PubMed:7716521}.

<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'>
|JUN kinase kinase activity|
|cellular response to sorbitol|
|negative regulation of motor neuron apoptotic process|
|regulation of motor neuron apoptotic process|
|response to sorbitol|
|physiological muscle hypertrophy|
|physiological cardiac muscle hypertrophy|
|cell growth involved in cardiac muscle cell development|
|positive regulation of smooth muscle cell apoptotic process|
|positive regulation of nitric-oxide synthase biosynthetic process|
|MAP kinase kinase activity|
|mitogen-activated protein kinase kinase kinase binding|
|regulation of nitric-oxide synthase biosynthetic process|
|regulation of smooth muscle cell apoptotic process|
|cardiac muscle tissue growth|
|heart growth|
|positive regulation of muscle cell apoptotic process|
|cardiac muscle hypertrophy|
|striated muscle hypertrophy|
|dendrite cytoplasm|
|muscle hypertrophy|
|positive regulation of DNA replication|
|activation of JUN kinase activity|
|positive regulation of neuron apoptotic process|
|cardiac muscle cell development|
|cardiac cell development|
|regulation of muscle cell apoptotic process|
|positive regulation of JUN kinase activity|
|cellular response to mechanical stimulus|
|cellular response to carbohydrate stimulus|
|JNK cascade|
|regulation of JUN kinase activity|
|developmental cell growth|
|cardiac muscle cell differentiation|
|protein tyrosine kinase activity|
|cell growth|
|positive regulation of neuron death|
|organ growth|
|stress-activated MAPK cascade|
|regulation of DNA replication|
|cardiocyte differentiation|
|perikaryon|
|striated muscle cell development|
|positive regulation of JNK cascade|
|stress-activated protein kinase signaling cascade|
|peptidyl-tyrosine phosphorylation|
|negative regulation of neuron apoptotic process|
|peptidyl-tyrosine modification|
|muscle cell development|
|activation of MAPK activity|
|cardiac muscle tissue development|
|positive regulation of stress-activated MAPK cascade|
|positive regulation of stress-activated protein kinase signaling cascade|
|response to carbohydrate|
|Fc-epsilon receptor signaling pathway|
|regulation of JNK cascade|
|striated muscle cell differentiation|
|regulation of neuron apoptotic process|
|negative regulation of neuron death|
|response to mechanical stimulus|
|regulation of stress-activated MAPK cascade|
|regulation of stress-activated protein kinase signaling cascade|
|protein kinase activity|
|Fc receptor signaling pathway|
|muscle cell differentiation|
|positive regulation of MAP kinase activity|
|striated muscle tissue development|
|axon|
|muscle tissue development|
|muscle system process|
|regulation of neuron death|
|cellular response to environmental stimulus|
|cellular response to abiotic stimulus|
|activation of protein kinase activity|
|cellular response to external stimulus|
|positive regulation of protein serine/threonine kinase activity|
|regulation of MAP kinase activity|
|protein serine/threonine kinase activity|
|MAPK cascade|
|developmental growth|
|growth|
|signal transduction by protein phosphorylation|
|muscle structure development|
|immune response-regulating cell surface receptor signaling pathway|
|regulation of protein serine/threonine kinase activity|
|heart development|
|positive regulation of protein kinase activity|
|positive regulation of MAPK cascade|
|response to wounding|
|positive regulation of kinase activity|
|immune response-regulating signaling pathway|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|positive regulation of transferase activity|
|positive regulation of cell death|
|regulation of cellular response to stress|
|regulation of MAPK cascade|
|regulation of protein kinase activity|
|circulatory system development|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|apoptotic process|
|protein phosphorylation|
|regulation of transferase activity|
|negative regulation of cell death|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|programmed cell death|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|cell death|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|regulation of immune response|
|response to abiotic stimulus|
|positive regulation of protein modification process|
|phosphorylation|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|regulation of response to stress|
|ATP binding|
|regulation of apoptotic process|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|cell development|
|regulation of immune system process|
|positive regulation of signal transduction|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|tissue development|
|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|
|positive regulation of macromolecule biosynthetic process|
|system process|
|positive regulation of cellular biosynthetic process|
|positive regulation of biosynthetic process|
</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: 0/739
^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>**: 12034
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.03 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='MAP2K4 Expression in NALM6 Cells: 5.03'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>