EIF2AK2
UniProt ID: P19525
Entrez ID: 5610
Protein name: Interferon-induced, double-stranded RNA-activated protein kinase (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 2) (eIF-2A protein kinase 2) (Interferon-inducible RNA-dependent protein kinase) (P1/eIF-2A protein kinase) (Protein kinase RNA-activated) (PKR) (Protein kinase R) (Tyrosine-protein kinase EIF2AK2) (EC 2.7.10.2) (p68 kinase)
External links: UniprotKB HGNC RefSeq COSMIC
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FUNCTION: IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection (PubMed:18835251, PubMed:19507191, PubMed:19189853, Pub...
FUNCTION: IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection (PubMed:18835251, PubMed:19507191, PubMed:19189853, PubMed:21123651, PubMed:21072047, PubMed:22948139, PubMed:23229543, PubMed:22381929). Inhibits viral replication via the integrated stress response (ISR): EIF2S1/eIF-2-alpha phosphorylation in response to viral infection converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resulting to a shutdown of cellular and viral protein synthesis, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4 (PubMed:19189853, PubMed:21123651, PubMed:22948139, PubMed:23229543). 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) (PubMed:11836380, PubMed:19189853, PubMed:20171114, PubMed:19840259, PubMed:21710204, PubMed:23115276, PubMed:23399035). Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11 (PubMed:11836380, PubMed:22214662, PubMed:19229320). 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 (PubMed:20395957). 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 pro-inflammatory cytokines and IFNs (PubMed:22948139, PubMed:23084476, PubMed:23372823). 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 (PubMed:10848580, PubMed:15121867, PubMed:15229216). Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) (PubMed:20685959). 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) (PubMed:20685959). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes (PubMed:22801494). Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin (By similarity). {ECO:0000250|UniProtKB:Q03963, 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, ECO:0000269|PubMed:32197074}.
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GO - Biological processes (BP):
cellular response to amino acid starvation [GO:0034198]; defense response to virus [GO:0051607]; endoplasmic reticulum unfolded protein response [GO:0030968]; innate immune response [GO:0045087]; negative regulation of apoptotic process [GO:0043066]; negative regulation of cell population proliferat...
cellular response to amino acid starvation [GO:0034198]; defense response to virus [GO:0051607]; endoplasmic reticulum unfolded protein response [GO:0030968]; innate immune response [GO:0045087]; negative regulation of apoptotic process [GO:0043066]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of osteoblast proliferation [GO:0033689]; negative regulation of translation [GO:0017148]; negative regulation of viral genome replication [GO:0045071]; positive regulation of chemokine production [GO:0032722]; positive regulation of cytokine production [GO:0001819]; positive regulation of MAPK cascade [GO:0043410]; positive regulation of NF-kappaB transcription factor activity [GO:0051092]; positive regulation of NIK/NF-kappaB signaling [GO:1901224]; positive regulation of stress-activated MAPK cascade [GO:0032874]; protein autophosphorylation [GO:0046777]; protein phosphorylation [GO:0006468]; regulation of hematopoietic progenitor cell differentiation [GO:1901532]; regulation of hematopoietic stem cell differentiation [GO:1902036]; regulation of hematopoietic stem cell proliferation [GO:1902033]; regulation of NLRP3 inflammasome complex assembly [GO:1900225]; response to interferon-alpha [GO:0035455]; response to virus [GO:0009615]; translation [GO:0006412]
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GO - Molecular function (MF):
ATP binding [GO:0005524]; double-stranded RNA binding [GO:0003725]; eukaryotic translation initiation factor 2alpha kinase activity [GO:0004694]; identical protein binding [GO:0042802]; non-membrane spanning protein tyrosine kinase activity [GO:0004715]; protein kinase activity [GO:0004672]; protein...
ATP binding [GO:0005524]; double-stranded RNA binding [GO:0003725]; eukaryotic translation initiation factor 2alpha kinase activity [GO:0004694]; identical protein binding [GO:0042802]; non-membrane spanning protein tyrosine kinase activity [GO:0004715]; protein kinase activity [GO:0004672]; protein phosphatase regulator activity [GO:0019888]; protein serine/threonine/tyrosine kinase activity [GO:0004712]; protein serine/threonine kinase activity [GO:0004674]; protein serine kinase activity [GO:0106310]; RNA binding [GO:0003723]
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GO - Cellular component (CC):
cytoplasm [GO:0005737]; cytosol [GO:0005829]; membrane [GO:0016020]; nucleus [GO:0005634]; perinuclear region of cytoplasm [GO:0048471]; ribosome [GO:0005840]...
cytoplasm [GO:0005737]; cytosol [GO:0005829]; membrane [GO:0016020]; nucleus [GO:0005634]; perinuclear region of cytoplasm [GO:0048471]; ribosome [GO:0005840]
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EIF2AK2
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Kaplan plot for EIF2AK2 in
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*NOTE: the Kaplan plots were collected from OncoLnc