EIF2AK2
Entrez ID: 5610
Full name: eukaryotic translation initiation factor 2 alpha kinase 2
External links: HGNC UniprotKB Ensembl RefSeq COSMIC
Family: Other: PEK: PKR
Chromosomal location: 2p22.2
Substructure location: Gatekeeper: 366 A-loop: 431...440, 442...453 G-loop: [N/A] αC-helix: 303...305
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EIF2AK2
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 a...
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.
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GO - Biological processes (BP):
activation of MAPKK activity, cellular response to amino acid starvation, defense response to virus, endoplasmic reticulum unfolded protein response, innate immune response, mitigation of host immune response by virus, negative regulation of apoptotic process, negative regulation of cell population ...
activation of MAPKK activity, cellular response to amino acid starvation, defense response to virus, endoplasmic reticulum unfolded protein response, innate immune response, mitigation of host immune response by virus, negative regulation of apoptotic process, negative regulation of cell population proliferation, negative regulation of osteoblast proliferation, negative regulation of translation, negative regulation of viral genome replication, positive regulation of chemokine production, positive regulation of cytokine production, positive regulation of NF-kappaB transcription factor activity, positive regulation of NIK/NF-kappaB signaling, positive regulation of stress-activated MAPK cascade, protein autophosphorylation, protein phosphorylation, regulation of hematopoietic progenitor cell differentiation, regulation of hematopoietic stem cell differentiation, regulation of hematopoietic stem cell proliferation, regulation of NLRP3 inflammasome complex assembly, response to interferon-alpha, response to virus, translation
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GO - Molecular function (MF):
ATP binding, double-stranded RNA binding, eukaryotic translation initiation factor 2alpha kinase activity, identical protein binding, non-membrane spanning protein tyrosine kinase activity, protein kinase activity, protein phosphatase regulator activity, protein serine/threonine kinase activity, RNA...
ATP binding, double-stranded RNA binding, eukaryotic translation initiation factor 2alpha kinase activity, identical protein binding, non-membrane spanning protein tyrosine kinase activity, protein kinase activity, protein phosphatase regulator activity, protein serine/threonine kinase activity, RNA binding
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GO - Cellular component (CC):
cytosol, nucleus, cytoplasm, membrane, perinuclear region of cytoplasm, ribosome...
cytosol, nucleus, cytoplasm, membrane, perinuclear region of cytoplasm, ribosome
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eukaryotic translation initiation factor 2 alpha kinase 2
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Kaplan plot for EIF2AK2 in
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*NOTE: the Kaplan plots were collected from OncoLnc