Browse EIF2AK2

Summary
SymbolEIF2AK2
Nameeukaryotic translation initiation factor 2-alpha kinase 2
Aliases PPP1R83; protein phosphatase 1, regulatory subunit 83; PRKR; protein kinase, interferon-inducible double str ......
Chromosomal Location2p22-p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm. Nucleus. Cytoplasm, perinuclear region. Note=Nuclear localization is elevated in acute leukemia, myelodysplastic syndrome (MDS), melanoma, breast, colon, prostate and lung cancer patient samples or cell lines as well as neurocytes from advanced Creutzfeldt-Jakob disease patients.
Domain PF00035 Double-stranded RNA binding motif
PF00069 Protein kinase domain
Function

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.

> Gene Ontology
 
Biological Process GO:0000186 activation of MAPKK activity
GO:0001819 positive regulation of cytokine production
GO:0002244 hematopoietic progenitor cell differentiation
GO:0002683 negative regulation of immune system process
GO:0002697 regulation of immune effector process
GO:0002698 negative regulation of immune effector process
GO:0002831 regulation of response to biotic stimulus
GO:0002832 negative regulation of response to biotic stimulus
GO:0006413 translational initiation
GO:0006417 regulation of translation
GO:0006446 regulation of translational initiation
GO:0006470 protein dephosphorylation
GO:0006986 response to unfolded protein
GO:0009267 cellular response to starvation
GO:0009615 response to virus
GO:0009636 response to toxic substance
GO:0009991 response to extracellular stimulus
GO:0010608 posttranscriptional regulation of gene expression
GO:0010921 regulation of phosphatase activity
GO:0010998 regulation of translational initiation by eIF2 alpha phosphorylation
GO:0016311 dephosphorylation
GO:0017148 negative regulation of translation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0019048 modulation by virus of host morphology or physiology
GO:0019049 evasion or tolerance of host defenses by virus
GO:0019058 viral life cycle
GO:0019079 viral genome replication
GO:0020012 evasion or tolerance of host immune response
GO:0030682 evasion or tolerance of host defense response
GO:0030683 evasion or tolerance by virus of host immune response
GO:0030968 endoplasmic reticulum unfolded protein response
GO:0031098 stress-activated protein kinase signaling cascade
GO:0031348 negative regulation of defense response
GO:0031667 response to nutrient levels
GO:0031668 cellular response to extracellular stimulus
GO:0031669 cellular response to nutrient levels
GO:0032102 negative regulation of response to external stimulus
GO:0032147 activation of protein kinase activity
GO:0032602 chemokine production
GO:0032642 regulation of chemokine production
GO:0032722 positive regulation of chemokine production
GO:0032872 regulation of stress-activated MAPK cascade
GO:0032874 positive regulation of stress-activated MAPK cascade
GO:0033674 positive regulation of kinase activity
GO:0033687 osteoblast proliferation
GO:0033688 regulation of osteoblast proliferation
GO:0033689 negative regulation of osteoblast proliferation
GO:0034047 regulation of protein phosphatase type 2A activity
GO:0034198 cellular response to amino acid starvation
GO:0034248 regulation of cellular amide metabolic process
GO:0034249 negative regulation of cellular amide metabolic process
GO:0034620 cellular response to unfolded protein
GO:0034976 response to endoplasmic reticulum stress
GO:0035303 regulation of dephosphorylation
GO:0035304 regulation of protein dephosphorylation
GO:0035455 response to interferon-alpha
GO:0035821 modification of morphology or physiology of other organism
GO:0035966 response to topologically incorrect protein
GO:0035967 cellular response to topologically incorrect protein
GO:0038061 NIK/NF-kappaB signaling
GO:0042594 response to starvation
GO:0043254 regulation of protein complex assembly
GO:0043405 regulation of MAP kinase activity
GO:0043410 positive regulation of MAPK cascade
GO:0043555 regulation of translation in response to stress
GO:0043558 regulation of translational initiation in response to stress
GO:0043666 regulation of phosphoprotein phosphatase activity
GO:0043900 regulation of multi-organism process
GO:0043901 negative regulation of multi-organism process
GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism
GO:0044003 modification by symbiont of host morphology or physiology
GO:0044413 avoidance of host defenses
GO:0044415 evasion or tolerance of host defenses
GO:0044546 NLRP3 inflammasome complex assembly
GO:0045069 regulation of viral genome replication
GO:0045071 negative regulation of viral genome replication
GO:0045860 positive regulation of protein kinase activity
GO:0046777 protein autophosphorylation
GO:0048525 negative regulation of viral process
GO:0048863 stem cell differentiation
GO:0050687 negative regulation of defense response to virus
GO:0050688 regulation of defense response to virus
GO:0050690 regulation of defense response to virus by virus
GO:0050792 regulation of viral process
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051403 stress-activated MAPK cascade
GO:0051607 defense response to virus
GO:0051701 interaction with host
GO:0051805 evasion or tolerance of immune response of other organism involved in symbiotic interaction
GO:0051807 evasion or tolerance of defense response of other organism involved in symbiotic interaction
GO:0051817 modification of morphology or physiology of other organism involved in symbiotic interaction
GO:0051832 avoidance of defenses of other organism involved in symbiotic interaction
GO:0051834 evasion or tolerance of defenses of other organism involved in symbiotic interaction
GO:0052173 response to defenses of other organism involved in symbiotic interaction
GO:0052200 response to host defenses
GO:0052564 response to immune response of other organism involved in symbiotic interaction
GO:0052572 response to host immune response
GO:0060218 hematopoietic stem cell differentiation
GO:0070302 regulation of stress-activated protein kinase signaling cascade
GO:0070304 positive regulation of stress-activated protein kinase signaling cascade
GO:0071425 hematopoietic stem cell proliferation
GO:0071496 cellular response to external stimulus
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0072089 stem cell proliferation
GO:0072091 regulation of stem cell proliferation
GO:0075136 response to host
GO:0098542 defense response to other organism
GO:1900225 regulation of NLRP3 inflammasome complex assembly
GO:1901222 regulation of NIK/NF-kappaB signaling
GO:1901224 positive regulation of NIK/NF-kappaB signaling
GO:1901532 regulation of hematopoietic progenitor cell differentiation
GO:1902033 regulation of hematopoietic stem cell proliferation
GO:1902036 regulation of hematopoietic stem cell differentiation
GO:1903706 regulation of hemopoiesis
GO:1903900 regulation of viral life cycle
GO:1903901 negative regulation of viral life cycle
GO:2000736 regulation of stem cell differentiation
Molecular Function GO:0003725 double-stranded RNA binding
GO:0004674 protein serine/threonine kinase activity
GO:0004694 eukaryotic translation initiation factor 2alpha kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004715 non-membrane spanning protein tyrosine kinase activity
GO:0008601 protein phosphatase type 2A regulator activity
GO:0019208 phosphatase regulator activity
GO:0019888 protein phosphatase regulator activity
Cellular Component GO:0005840 ribosome
> KEGG and Reactome Pathway
 
KEGG hsa04141 Protein processing in endoplasmic reticulum
Reactome R-HSA-168276: NS1 Mediated Effects on Host Pathways
R-HSA-1169410: Antiviral mechanism by IFN-stimulated genes
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-1643685: Disease
R-HSA-168253: Host Interactions with Influenza Factors
R-HSA-1169408: ISG15 antiviral mechanism
R-HSA-168256: Immune System
R-HSA-5663205: Infectious disease
R-HSA-168254: Influenza Infection
R-HSA-169131: Inhibition of PKR
R-HSA-913531: Interferon Signaling
Summary
SymbolEIF2AK2
Nameeukaryotic translation initiation factor 2-alpha kinase 2
Aliases PPP1R83; protein phosphatase 1, regulatory subunit 83; PRKR; protein kinase, interferon-inducible double str ......
Chromosomal Location2p22-p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between EIF2AK2 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 

There is no record.
Summary
SymbolEIF2AK2
Nameeukaryotic translation initiation factor 2-alpha kinase 2
Aliases PPP1R83; protein phosphatase 1, regulatory subunit 83; PRKR; protein kinase, interferon-inducible double str ......
Chromosomal Location2p22-p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of EIF2AK2 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 STARS Score: 10.46; FDR: 0.000 Sensitive to T cell-mediated killing
28723893CRISPR-Cas9 melanomaB16GVAX STARS Score: 12.37; FDR: 0.000 Sensitive to T cell-mediated killing
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolEIF2AK2
Nameeukaryotic translation initiation factor 2-alpha kinase 2
Aliases PPP1R83; protein phosphatase 1, regulatory subunit 83; PRKR; protein kinase, interferon-inducible double str ......
Chromosomal Location2p22-p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of EIF2AK2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.1950.438
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.0320.981
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.3210.776
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.0210.945
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.0040.999
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.0520.984
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1660.69
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.2040.897
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.1250.943
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.5330.631
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.8060.628
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0770.277
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of EIF2AK2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.71.42.30.469
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.71.720.532
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.55.93.61
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131115.49.16.31
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.63.7-1.11
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 221307.7-7.70.371
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolEIF2AK2
Nameeukaryotic translation initiation factor 2-alpha kinase 2
Aliases PPP1R83; protein phosphatase 1, regulatory subunit 83; PRKR; protein kinase, interferon-inducible double str ......
Chromosomal Location2p22-p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of EIF2AK2. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolEIF2AK2
Nameeukaryotic translation initiation factor 2-alpha kinase 2
Aliases PPP1R83; protein phosphatase 1, regulatory subunit 83; PRKR; protein kinase, interferon-inducible double str ......
Chromosomal Location2p22-p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of EIF2AK2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by EIF2AK2.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolEIF2AK2
Nameeukaryotic translation initiation factor 2-alpha kinase 2
Aliases PPP1R83; protein phosphatase 1, regulatory subunit 83; PRKR; protein kinase, interferon-inducible double str ......
Chromosomal Location2p22-p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of EIF2AK2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolEIF2AK2
Nameeukaryotic translation initiation factor 2-alpha kinase 2
Aliases PPP1R83; protein phosphatase 1, regulatory subunit 83; PRKR; protein kinase, interferon-inducible double str ......
Chromosomal Location2p22-p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of EIF2AK2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolEIF2AK2
Nameeukaryotic translation initiation factor 2-alpha kinase 2
Aliases PPP1R83; protein phosphatase 1, regulatory subunit 83; PRKR; protein kinase, interferon-inducible double str ......
Chromosomal Location2p22-p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between EIF2AK2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolEIF2AK2
Nameeukaryotic translation initiation factor 2-alpha kinase 2
Aliases PPP1R83; protein phosphatase 1, regulatory subunit 83; PRKR; protein kinase, interferon-inducible double str ......
Chromosomal Location2p22-p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting EIF2AK2 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.