EIF2AK2 (PKR) – Interferon-Induced Double-Stranded RNA-Activated Protein Kinase
Key regulator of antiviral innate immunity, translation control, and apoptosis; implicated in cancer and neurodegenerative disorders.
Gene Information Card
| Symbol | EIF2AK2 |
|---|---|
| Full Name | Eukaryotic Translation Initiation Factor 2 Alpha Kinase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 2p22.2 |
| NCBI Gene ID | 5610 ncbi.nlm.nih.gov/gene/5610 |
| Ensembl ID | ENSG00000055332 |
| UniProt ID | P19525 |
| OMIM ID | 176871 |
| HGNC ID | 3255 |
| Aliases | PKR, PRKR, EIF2AK1 |
Description
EIF2AK2 encodes the interferon-induced double-stranded RNA-activated protein kinase (PKR). PKR is a serine/threonine kinase that phosphorylates eukaryotic translation initiation factor 2 subunit alpha (eIF2α) on Ser51, leading to inhibition of global protein synthesis. It plays a central role in antiviral defense, stress responses, apoptosis, and cell proliferation. PKR is activated by double-stranded RNA (dsRNA) produced during viral infection, as well as by cellular stresses such as growth factor deprivation, cytokines, and oxidative stress. The gene is located on chromosome 2p22.2 and spans approximately 50 kb.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | PKR downregulation or loss-of-function mutations impair eIF2α phosphorylation, promoting unchecked translation and tumor growth. | PMID: 23542344; COSMIC |
| Breast cancer | Reduced PKR expression correlates with poor prognosis; gain-of-function mutations may contribute to chemoresistance. | PMID: 19029980; ClinVar |
| Alzheimer disease | PKR activation and increased eIF2α phosphorylation are observed in affected brain regions, linking to synaptic dysfunction and tau pathology. | PMID: 23152622; OMIM 176871 |
| Viral infections (e.g., influenza, HIV) | Viruses encode dsRNA-binding proteins or inhibitors to block PKR activation, enabling viral replication. | PMID: 15567474; UniProt P19525 |
| Inflammatory bowel disease | PKR polymorphisms associated with increased susceptibility; altered PKR signaling may affect intestinal epithelial barrier function. | PMID: 21217753; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Liver | 8.2 | Medium |
| Brain (cortex) | 6.1 | Low |
| Heart | 4.3 | Low |
| Kidney | 7.9 | Medium |
| Pancreas | 5.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 15.2 | High expression; used in PKR activation studies |
| HEK293 (embryonic kidney) | 11.0 | Moderate; common for overexpression |
| HepG2 (hepatocellular carcinoma) | 9.8 | Moderate; relevant for liver cancer models |
| A549 (lung carcinoma) | 13.1 | High; responsive to dsRNA stimulation |
| SH-SY5Y (neuroblastoma) | 7.4 | Low; used in neurodegeneration research |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1070G>A (p.Arg357His) | Missense | 0.02% (gnomAD) | Reduced kinase activity; associated with increased cancer risk (ClinVar) |
| c.1465C>T (p.Arg489Trp) | Missense | 0.01% (gnomAD) | Impaired eIF2α phosphorylation; loss-of-function (COSMIC) |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Likely loss-of-function; reported in hepatocellular carcinoma (COSMIC) |
| c.1642C>T (p.Arg548Cys) | Missense | 0.005% | Gain-of-function? Increased apoptosis in vitro (UniProt) |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish PKR kinase activity (e.g., p.Arg357His, p.Arg489Trp) impair eIF2α phosphorylation, leading to unchecked protein synthesis and potential oncogenic transformation.
Gain of Function (GOF)
Rare variants (e.g., p.Arg548Cys) may enhance PKR activity, promoting excessive eIF2α phosphorylation and apoptosis, possibly contributing to neurodegenerative phenotypes.
Dominant Negative (DN)
Certain missense mutations (e.g., p.Lys296Arg) can form inactive dimers that sequester wild-type PKR, reducing overall cellular PKR activity.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Interferon signaling (Reactome R-HSA-913531)
• PKR-mediated eIF2α phosphorylation (Reactome R-HSA-168927)
• Apoptosis (KEGG hsa04210)
• RIG-I/MDA5 mediated induction of IFN-alpha/beta (Reactome R-HSA-168928)
Protein Summary
PKR is a 551-amino-acid protein (68 kDa) containing an N-terminal double-stranded RNA-binding domain (dsRBD) and a C-terminal kinase domain. Upon binding dsRNA, PKR dimerizes and autophosphorylates, becoming active. Active PKR phosphorylates eIF2α on Ser51, which inhibits the guanine nucleotide exchange factor eIF2B, blocking translation initiation. PKR also interacts with other signaling molecules (e.g., NF-κB, p53) to modulate apoptosis and inflammation. The protein is expressed ubiquitously, with highest levels in lymphoid tissues and lung. Post-translational modifications include phosphorylation at Thr446 and Thr451 in the activation loop.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EIF2AK2 Knockout HEK293 Cell Line | EDJ-KQ2040 | Human | 5610 | Details Get a Quote |
| EIF2AK2 Knockout A-549 Cell Line | EDJ-KQ22083 | Human | 5610 | Details Get a Quote |
| EIF2AK2 Knockout HCT 116 Cell Line | EDJ-KQ22084 | Human | 5610 | Details Get a Quote |
| EIF2AK2 Knockout HeLa Cell Line | EDJ-KQ22085 | Human | 5610 | Details Get a Quote |
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