EIF2AK2 [The Human Chemical-Genetic Interaction Map Project]

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======= EIF2AK2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: EIF2AK2
  * **<color #00a2e8>Official Name</color>**: eukaryotic translation initiation factor 2 alpha kinase 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5610|5610]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P19525|P19525]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=EIF2AK2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20EIF2AK2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/176871|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene is a serine/threonine protein kinase that is activated by autophosphorylation after binding to dsRNA. The activated form of the encoded protein can phosphorylate translation initiation factor EIF2S1, which in turn inhibits protein synthesis. This protein is also activated by manganese ions and heparin. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]. 
  * **<color #00a2e8>UniProt Summary</color>**:  IFN-induced dsRNA-dependent serine/threonine-protein kinase which plays a key role in the innate immune response to viral infection and is also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation. Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1). Inhibits viral replication via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (EIF2S1), this phosphorylation impairs the recycling of EIF2S1 between successive rounds of initiation leading to inhibition of translation which eventually results in shutdown of cellular and viral protein synthesis. Also phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11. In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteosomal degradation. Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding proinflammatory cytokines and IFNs. Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6. Can act as both a positive and negative regulator of the insulin signaling pathway (ISP). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser- 312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes. Can trigger apoptosis via FADD-mediated activation of CASP8. Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin. {ECO:0000269|PubMed:10848580, ECO:0000269|PubMed:11836380, ECO:0000269|PubMed:15121867, ECO:0000269|PubMed:15229216, ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:19189853, ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:19507191, ECO:0000269|PubMed:19840259, ECO:0000269|PubMed:20171114, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20685959, ECO:0000269|PubMed:21072047, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:21710204, ECO:0000269|PubMed:22214662, ECO:0000269|PubMed:22381929, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:22948139, ECO:0000269|PubMed:23084476, ECO:0000269|PubMed:23115276, ECO:0000269|PubMed:23229543, ECO:0000269|PubMed:23372823, ECO:0000269|PubMed:23399035}.

<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'>
|dsrm|
|Pkinase Tyr|
|Pkinase|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|evasion or tolerance by virus of host immune response|
|evasion or tolerance of immune response of other organism involved in symbiotic interaction|
|evasion or tolerance of defense response of other organism involved in symbiotic interaction|
|evasion or tolerance of host immune response|
|evasion or tolerance of host defense response|
|regulation of translational initiation by eIF2 alpha phosphorylation|
|eukaryotic translation initiation factor 2alpha kinase activity|
|evasion or tolerance of host defenses by virus|
|response to immune response of other organism involved in symbiotic interaction|
|response to host immune response|
|evasion or tolerance of host defenses|
|evasion or tolerance of defenses of other organism involved in symbiotic interaction|
|avoidance of host defenses|
|avoidance of defenses of other organism involved in symbiotic interaction|
|response to host|
|response to defenses of other organism involved in symbiotic interaction|
|response to host defenses|
|regulation of hematopoietic stem cell proliferation|
|cytosolic ribosome|
|negative regulation of osteoblast proliferation|
|regulation of translational initiation in response to stress|
|regulation of NLRP3 inflammasome complex assembly|
|regulation of translation in response to stress|
|response to interferon-alpha|
|regulation of osteoblast proliferation|
|regulation of defense response to virus by virus|
|modulation by virus of host morphology or physiology|
|protein phosphatase regulator activity|
|modification by symbiont of host morphology or physiology|
|cellular response to amino acid starvation|
|ribosome|
|non-membrane spanning protein tyrosine kinase activity|
|response to amino acid starvation|
|activation of MAPKK activity|
|positive regulation of chemokine production|
|negative regulation of viral genome replication|
|regulation of stem cell proliferation|
|double-stranded RNA binding|
|regulation of hematopoietic stem cell differentiation|
|positive regulation of NIK/NF-kappaB signaling|
|regulation of chemokine production|
|regulation of translational initiation|
|negative regulation of viral life cycle|
|regulation of hematopoietic progenitor cell differentiation|
|regulation of viral genome replication|
|negative regulation of viral process|
|endoplasmic reticulum unfolded protein response|
|regulation of NIK/NF-kappaB signaling|
|modification of morphology or physiology of other organism involved in symbiotic interaction|
|regulation of stem cell differentiation|
|regulation of phosphoprotein phosphatase activity|
|cellular response to unfolded protein|
|negative regulation of translation|
|regulation of protein dephosphorylation|
|peptidyl-tyrosine phosphorylation|
|regulation of viral life cycle|
|negative regulation of cellular amide metabolic process|
|peptidyl-tyrosine modification|
|cellular response to topologically incorrect protein|
|cellular response to starvation|
|positive regulation of NF-kappaB transcription factor activity|
|modification of morphology or physiology of other organism|
|interaction with host|
|response to unfolded protein|
|positive regulation of stress-activated MAPK cascade|
|positive regulation of stress-activated protein kinase signaling cascade|
|regulation of phosphatase activity|
|response to topologically incorrect protein|
|defense response to virus|
|protein autophosphorylation|
|response to starvation|
|regulation of viral process|
|regulation of dephosphorylation|
|negative regulation of multi-organism process|
|regulation of symbiosis, encompassing mutualism through parasitism|
|regulation of stress-activated MAPK cascade|
|cellular response to nutrient levels|
|regulation of stress-activated protein kinase signaling cascade|
|protein kinase activity|
|response to endoplasmic reticulum stress|
|positive regulation of MAP kinase activity|
|positive regulation of DNA-binding transcription factor activity|
|cellular response to extracellular stimulus|
|response to virus|
|activation of protein kinase activity|
|cellular response to external stimulus|
|positive regulation of protein serine/threonine kinase activity|
|regulation of MAP kinase activity|
|regulation of translation|
|protein serine/threonine kinase activity|
|translation|
|regulation of cellular amide metabolic process|
|peptide biosynthetic process|
|regulation of DNA-binding transcription factor activity|
|positive regulation of cytokine production|
|regulation of protein complex assembly|
|regulation of hemopoiesis|
|response to nutrient levels|
|regulation of protein serine/threonine kinase activity|
|posttranscriptional regulation of gene expression|
|amide biosynthetic process|
|peptide metabolic process|
|response to extracellular stimulus|
|positive regulation of protein kinase activity|
|positive regulation of MAPK cascade|
|positive regulation of kinase activity|
|positive regulation of transferase activity|
|negative regulation of cell population proliferation|
|regulation of cytokine production|
|perinuclear region of cytoplasm|
|viral process|
|regulation of cellular response to stress|
|regulation of MAPK cascade|
|innate immune response|
|regulation of multi-organism process|
|symbiotic process|
|cellular amide metabolic process|
|regulation of protein kinase activity|
|interspecies interaction between organisms|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|defense response to other organism|
|regulation of cellular component biogenesis|
|protein phosphorylation|
|regulation of transferase activity|
|negative regulation of cell death|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|negative regulation of cellular protein metabolic process|
|positive regulation of phosphorylation|
|identical protein binding|
|immune effector process|
|response to cytokine|
|negative regulation of protein metabolic process|
|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|
|negative regulation of cellular macromolecule biosynthetic process|
|RNA binding|
|organonitrogen compound biosynthetic process|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|negative regulation of macromolecule biosynthetic process|
|regulation of response to stress|
|ATP binding|
|negative regulation of cellular biosynthetic process|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|cellular nitrogen compound biosynthetic process|
|positive regulation of signal transduction|
|regulation of immune system process|
|regulation of cell death|
|cellular response to stress|
|positive regulation of protein metabolic process|
|cellular macromolecule biosynthetic process|
|negative regulation of gene expression|
|positive regulation of multicellular organismal process|
|macromolecule biosynthetic 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|
|membrane|
|gene expression|
</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:exp52|Ribavirin 10μM R01 exp52]]|-2.08|
</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>**: 16108
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.01 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='EIF2AK2 Expression in NALM6 Cells: 7.01'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>