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- Table of Contents
Facts about Interferon-induced, double-stranded RNA-activated protein kinase.
Inhibits viral replication through phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (EIF2S1), this phosphorylation interrupts the recycling of EIF2S1 between successive rounds of initiation leading to inhibition of translation that 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.
Human | |
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Gene Name: | EIF2AK2 |
Uniprot: | P19525 |
Entrez: | 5610 |
Belongs to: |
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protein kinase superfamily |
double stranded RNA activated protein kinase; EC 2.7.11.1; eIF-2A protein kinase 2; EIF2AK1; EIF2AK2; eukaryotic translation initiation factor 2-alpha kinase 2P1/eIF-2A protein kinase; interferon-induced, double-stranded RNA-activated protein kinase; interferon-inducible double stranded RNA dependent; interferon-inducible elF2alpha kinase; Interferon-inducible RNA-dependent protein kinase; P68 Kinase; PKR; PKRp68 kinase; PPP1R83; PRKR; PRKRMGC126524; Protein Kinase R; Protein kinase RNA-activated
Mass (kDA):
62.094 kDA
Human | |
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Location: | 2p22.2 |
Sequence: | 2; NC_000002.12 (37099210..37157065, complement) |
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.
Cytoplasm. Nucleus. Cytoplasm, perinuclear region. 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.
The EIF2AK2 marker is used in a variety of biological tests. Boster Bio uses mouse and rabbit blood samples to make antibodies against the protein. Numerous animal cancers have elevated levels. These levels are usually associated with the progression and growth of cancerous tumors. This marker can help distinguish between cancers depending on their stage, and those with lower levels.
Gene infographics inspired by the Eif2AK2 marker provide basic information about each gene. This gene infographic series includes all genes that are found in both animals and humans. You can use the gene search bar to find the gene you are looking for. Below are some infographics about genes that use the EIF2AK2 marker.
Two-way analysis of variance (ANOVA), was performed to determine the expression of EIF2AK2 on skin biopsy samples taken from patients suffering from the mutation. We also collected fibroblast cell cultures from three donors with normal neurological functioning. Our results indicated that the mutation persists for more than 16 hours in patients' fibroblasts. The cells' response to IFN b was determined using biochemical tests.
We studied the cosegregation of the gene and found that one variant of this gene was homozygous in both females and males. The heterozygous variant, c.388G>A or p.Gly130Arg, is not found in any of the population databases and was predicted to be benign by the majority of in silico tools. The variant is located just 2 nucleotides from the exon-intron boundary. Our samples also didn't show evidence of mRNA-splicing errors.
Patients with this variant of the gene showed a very varied clinical phenotype. Nine patients had generalized dystonia , and six patients had isolated dystonia, with three developing mild intellectual disability. Seven patients were affected by axial involvement. Two patients also had neurological problems and spasticity as a result of their illness. Dystonia is a disorder that is monogenetic that is associated with the abnormalities of eIF2a signaling.
The Besta Institute cohort included E-II-3 the Italian patient, as well as 96 dystonia patients from Lubeck (Germany). The variant was confirmed via Sanger sequencing. To confirm the variant it was necessary to conduct a parent study done on the offspring of the patients. This case study is the first to establish the existence of a single variant in the EIF2AK2 gene , which is associated with generalized dystonia.
The EIF2AK2 gene is linked to early onset generalized dystonia, which is isolated. In a study of five patients from a Taiwanese family, a missense variant in the gene was associated with the onset of dystonia for three cases. The study also identified three missense variants within the gene, all located within the functional domains of encoded protein.
It is not clear what role EIF2AK2 plays in progression of the condition. However the gene has been implicated in neurodegeneration induced by HIV/gp120. It is a substrate of autophosphorylation and protein kinases. It is also involved in cell expansion, mRNA translation and apoptosis. Further research is needed to understand the role of EIF2AK2 in the development of this disease.
IBD is a popular term for a variety of relapsing inflammatory disorders. The disease is characterized by activation of the inflammasome however the mechanisms behind this remain unclear. Double-stranded, non-RNA-dependent proteinkinase (EIF2AK2) is the name given to the gene that encodes EIF2AK2. This gene has been associated with Alzheimer's disease by studies on genetics. More research is needed to determine its function in this condition.
The EIF2AK2 gene was first discovered by Barber et al. Barber and co. determined the EIF2AK2 gene's EIF2AK2 region to chromosome 21. Similar techniques were employed to map the mouse EIF2AK2 gene to chromosome 17 (band E2), but Squire and colleagues. The EIF2AK2 gene was assigned to the boundary between 2p22 and 21p21.
The spleen is home to large amounts of PrPres the molecule responsible for inflammation in the brain. These tissues were used to extract total RNA , and were examined in the same way as brain samples. There was no significant change in the levels of mRNA in the spleens. The results of the Alzheimer's disease research weren't applicable to human beings. This study can help future studies on this protein.
The EIF2AK2 gene's product is a human protein recombinant enzyme, connects to the DNA sequence. Its molecular weight (MW) is 64 kDa and it has a 252-amino tail. The protein was previously identified as a native meelin from swine. The EIF2AK2 marker's applications include cell proliferation and tumorigenesis.
The expression of the EIF2AK2 marker in pancreatic cancer correlates with the expression of STAT1 and interferon-stimulated genes. It also indicates a negative correlation between them, which is linked with a poor prognosis. The UCSC Xena browser summarizes studies that utilized the EIF2AK2 marker. These results require further validation.
PMID: 1695551 by Meurs E., et al. Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon.
PMID: 1373553 by Thomis D.C., et al. Mechanism of interferon action: cDNA structure, expression, and regulation of the interferon-induced, RNA-dependent P1/eIF-2 alpha protein kinase from human cells.