Summary of EIF2AK2
This gene encodes a protein that helps inhibits protein synthesis (R).
The Function of 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 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.
Protein names
Recommended name:
Interferon-induced, double-stranded RNA-activated protein kinaseShort name:
PKRAlternative name(s):
Eukaryotic translation initiation factor 2-alpha kinase 2eIF-2A protein kinase 2
Interferon-inducible RNA-dependent protein kinase
P1/eIF-2A protein kinase
Protein kinase RNA-activated
Protein kinase R
Tyrosine-protein kinase EIF2AK2
p68 kinase
- RS2254958 (EIF2AK2) ??
- RS4233921 (EIF2AK2) ??
To see your genotype, you should be logged in and have a file with your genotype uploaded.
Top Gene-Substance Interactions
EIF2AK2 Interacts with These Diseases
| Disease | Score |
Substances That Increase EIF2AK2
| Substances | Interaction | Organism | Category |
Substances That Decrease EIF2AK2
| Substances | Interaction | Organism | Category |
Conditions with Increased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
|---|
Conditions with Decreased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
|---|
Technical
The following transcription factors affect gene expression:
Tissue specificity:
Highly expressed in thymus, spleen and bone marrow compared to non-hematopoietic tissues such as small intestine, liver, or kidney tissues. Colocalizes with GSK3B and TAU in the Alzheimer disease (AD) brain. Elevated levels seen in breast and colon carcinomas,and which correlates with tumor progression and invasiveness or risk of progression.
Gene Pathways:
Induction:
By type I interferons.
Enzyme Regulation:
Initially produced in an inactive form and is activated by binding to viral dsRNA, which causes dimerization and autophosphorylation in the activation loop and stimulation of function. ISGylation can activate it in the absence of viral infection. Can also be activated by heparin, proinflammatory stimuli, growth factors, cytokines, oxidative stress and the cellular protein PRKRA. Activity is markedly stimulated by manganese ions. Activation is blocked by the viral components HIV-1 Tat protein and large amounts of HIV-1 trans-activation response (TAR) RNA element as well as by the cellular proteins TARBP2, DUS2L, NPM1, NCK1 and ADAR. Down-regulated by Toscana virus (TOS) and Rift valley fever virus (RVFV) NSS which promote its proteasomal degradation. Inhibited by vaccinia virus protein E3, probably via dsRNA sequestering.
Molecular Function:
- Atp Binding
- Double-Stranded Rna Binding
- Eukaryotic Translation Initiation Factor 2alpha Kinase Activity
- Non-Membrane Spanning Protein Tyrosine Kinase Activity
- Poly(A) Rna Binding
- Protein Phosphatase Type 2a Regulator Activity
- Protein Serine/Threonine Kinase Activity
Biological Processes:
- Activation Of Mapkk Activity
- Cellular Response To Amino Acid Starvation
- Defense Response To Virus
- Endoplasmic Reticulum Unfolded Protein Response
- Evasion Or Tolerance By Virus Of Host Immune Response
- Innate Immune Response
- Negative Regulation Of Apoptotic Process
- Negative Regulation Of Cell 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 Toxic Substance
- Response To Virus
- Transcription, Dna-Templated
- Translation
- Positive Regulation Of Apoptotic Process
- Response To Exogenous Dsrna
- Response To Lipopolysaccharide
- Response To Mechanical Stimulus
- Response To Vitamin E