======= EIF2AK3 =======
== Gene Information ==
* **Official Symbol**: EIF2AK3
* **Official Name**: eukaryotic translation initiation factor 2 alpha kinase 3
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=9451|9451]]
* **UniProt**: [[https://www.uniprot.org/uniprot/Q9NZJ5|Q9NZJ5]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=EIF2AK3&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20EIF2AK3|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/604032|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2, leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. This protein is thought to modulate mitochondrial function. It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. Mutations in this gene are associated with Wolcott-Rallison syndrome. [provided by RefSeq, Sep 2015].
* **UniProt Summary**: Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52' during the unfolded protein response (UPR) and in response to low amino acid availability. Converts phosphorylated eIF-2-alpha/EIF2S1 either in a global protein synthesis inhibitor, leading to a reduced overall utilization of amino acids, or to a translation initiation activator of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. Serves as a critical effector of unfolded protein response (UPR)- induced G1 growth arrest due to the loss of cyclin-D1 (CCND1). Involved in control of mitochondrial morphology and function. {ECO:0000250|UniProtKB:Q9Z2B5}.
|Pkinase Tyr|
|Pkinase|
|regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation|
|eiF2alpha phosphorylation in response to endoplasmic reticulum stress|
|response to manganese-induced endoplasmic reticulum stress|
|regulation of translation initiation in response to endoplasmic reticulum stress|
|eukaryotic translation initiation factor 2alpha kinase activity|
|regulation of translational initiation by eIF2 alpha phosphorylation|
|negative regulation of translational initiation in response to stress|
|regulation of translation in response to endoplasmic reticulum stress|
|negative regulation of translation in response to stress|
|cytosolic ribosome|
|negative regulation of myelination|
|cellular response to cold|
|regulation of translational initiation in response to stress|
|cellular response to manganese ion|
|PERK-mediated unfolded protein response|
|ER overload response|
|insulin-like growth factor receptor signaling pathway|
|regulation of translation in response to stress|
|negative regulation of translational initiation|
|response to manganese ion|
|positive regulation of transcription by RNA polymerase I|
|negative regulation of nervous system process|
|positive regulation of vascular endothelial growth factor production|
|regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway|
|regulation of transcription by RNA polymerase I|
|regulation of vascular endothelial growth factor production|
|ER-nucleus signaling pathway|
|endocrine pancreas development|
|Hsp90 protein binding|
|cellular response to glucose starvation|
|regulation of myelination|
|cellular response to amino acid starvation|
|chondrocyte development|
|response to amino acid starvation|
|bone mineralization|
|response to cold|
|endoplasmic reticulum organization|
|pancreas development|
|positive regulation of protein localization to nucleus|
|regulation of translational initiation|
|chondrocyte differentiation|
|regulation of response to endoplasmic reticulum stress|
|protein phosphatase binding|
|activation of cysteine-type endopeptidase activity involved in apoptotic process|
|biomineralization|
|biomineral tissue development|
|endoplasmic reticulum unfolded protein response|
|integral component of endoplasmic reticulum membrane|
|regulation of protein localization to nucleus|
|endocrine system development|
|cellular response to unfolded protein|
|negative regulation of translation|
|positive regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|regulation of nervous system process|
|calcium-mediated signaling|
|negative regulation of cellular amide metabolic process|
|cellular response to topologically incorrect protein|
|positive regulation of cysteine-type endopeptidase activity|
|cellular response to starvation|
|regulation of intrinsic apoptotic signaling pathway|
|response to unfolded protein|
|cartilage development|
|positive regulation of endopeptidase activity|
|peptidyl-serine phosphorylation|
|response to temperature stimulus|
|response to topologically incorrect protein|
|positive regulation of peptidase activity|
|cellular response to metal ion|
|response to starvation|
|protein autophosphorylation|
|peptidyl-serine modification|
|cellular response to biotic stimulus|
|regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|cellular response to inorganic substance|
|connective tissue development|
|cellular response to nutrient levels|
|protein kinase activity|
|regulation of cysteine-type endopeptidase activity|
|response to endoplasmic reticulum stress|
|ossification|
|cellular response to extracellular stimulus|
|negative regulation of nervous system development|
|angiogenesis|
|positive regulation of cellular protein localization|
|cellular response to external stimulus|
|second-messenger-mediated signaling|
|protein homooligomerization|
|enzyme binding|
|regulation of translation|
|positive regulation of proteolysis|
|protein serine/threonine kinase activity|
|response to metal ion|
|regulation of apoptotic signaling pathway|
|regulation of cellular amide metabolic process|
|blood vessel morphogenesis|
|regulation of endopeptidase activity|
|endomembrane system organization|
|regulation of peptidase activity|
|positive regulation of cytokine production|
|blood vessel development|
|skeletal system development|
|response to nutrient levels|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|vasculature development|
|cardiovascular system development|
|protein complex oligomerization|
|posttranscriptional regulation of gene expression|
|response to extracellular stimulus|
|response to inorganic substance|
|regulation of cellular protein localization|
|regulation of system process|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|tube morphogenesis|
|regulation of cytokine production|
|positive regulation of cell death|
|perinuclear region of cytoplasm|
|enzyme linked receptor protein signaling pathway|
|regulation of proteolysis|
|regulation of cellular response to stress|
|positive regulation of hydrolase activity|
|tube development|
|circulatory system development|
|protein homodimerization activity|
|peptidyl-amino acid modification|
|anatomical structure formation involved in morphogenesis|
|regulation of cellular localization|
|regulation of nervous system development|
|endoplasmic reticulum membrane|
|negative regulation of developmental process|
|protein phosphorylation|
|endoplasmic reticulum|
|regulation of protein localization|
|negative regulation of cellular protein metabolic process|
|identical protein binding|
|negative regulation of protein metabolic process|
|response to abiotic stimulus|
|negative regulation of multicellular organismal process|
|regulation of hydrolase activity|
|phosphorylation|
|response to biotic stimulus|
|negative regulation of cellular macromolecule 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|
|positive regulation of transcription, DNA-templated|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|protein-containing complex assembly|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|cell development|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|tissue development|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|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|
|membrane|
|positive regulation of biosynthetic process|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp8|Brefeldin A 0.02μM R00 exp8]]|-3.05|
|[[:results:exp416|Tubacin 1.6μM R07 exp416]]|-2.24|
|[[:results:exp502|Milciclib 2μM R08 exp502]]|1.75|
|[[:results:exp499|LY2090314 0.003μM R08 exp499]]|1.79|
|[[:results:exp436|Dynasore 7μM R08 exp436]]|1.95|
|[[:results:exp504|MK2206 4μM R08 exp504]]|2|
|[[:results:exp234|Ethanol 0.01 R05 exp234]]|2.07|
|[[:results:exp134|MS023 2μM R03 exp134]]|2.09|
|[[:results:exp70|INK128 0.2μM R02 exp70]]|2.12|
|[[:results:exp334|All-trans-Retinoic-Acid 40μM R07 exp334]]|2.13|
|[[:results:exp269|Bisphenol A 100μM R06 exp269]]|2.27|
|[[:results:exp122|Golgicide-A 4μM R03 exp122]]|2.57|
|[[:results:exp498|Lead acetate 2000μM R08 exp498 no dilution day6]]|2.7|
|[[:results:exp497|Lead acetate 2000μM R08 exp497]]|2.77|
|[[:results:exp418|Tunicamycin 0.04μM R07 exp418]]|3.47|
|[[:results:exp420|Tunicamycin 0.04 to 0.125μM on day4 R07 exp420]]|3.71|
|[[:results:exp419|Tunicamycin 0.04 to 0.075μM on day4 R07 exp419]]|4.42|
No correlation found to any other genes in chemogenomics.
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|1/15|
|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**: 9679
* **Expression level (log2 read counts)**: 7.14
{{:chemogenomics:nalm6 dist.png?nolink |}}