EIF2AK2 — Eukaryotic translation initiation factor 2 alpha kinase 2
EIF2AK2 belongs to a gene co-expression module in 7 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
EIF2AK2's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| CD4⁺ T cells | Interferon response Anti-viral | ACBD5, AQP3, BTN2A1, BTN3A2, BTN3A3, CISH, ERAP2, GBP1 +23 more | View in SCUBA |
| CD8⁺ T cells | Type I Interferon Inflammation | BST2, CHMP5, LAP3, NAPA, NMI, OASL, PLSCR1, SPATS2L +1 more | View in SCUBA |
| Gamma-delta T cells | Translation & Proteostasis RNA processing & translation | ARAP2, ATG13, BRPF1, CLINT1, CRKL, E2F3, EEF2, EIF2S3 +15 more | |
| Innate lymphoid cells | Pyruvate Metabolism Metabolism | ABCB1, ADI1, ARID1B, ATF7IP2, CFAP298, HNRNPH3, MINDY2, MPC2 +10 more | View in SCUBA |
| Lymphatic endothelial | Innate Immune Activation Immune regulation | CD46, CLTC, CRIM1, ENSA, FEZ2, GSN, PDLIM3, PON2 +9 more | View in SCUBA |
| Macrophages | Antiviral ISG Response Antiviral | ADAR, APOL6, ARID5A, CLEC7A, DDX60, DTX3L, ERICH1, IFIH1 +29 more | View in SCUBA |
| Mucosal-associated invariant T cell | Type I Interferon Inflammation | DDX60, DDX60L, DTX3L, EPSTI1, GBP2, GBP4, HERC5, IFI16 +18 more |
About the gene
| Synonyms | PKR, PPP1R83, PRKR |
|---|---|
| Chromosome | 2: 37099210-37157522 |
| Predicted location | Intracellular |
| Essential gene | No |
| Protein class | Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins |
| Molecular function | Kinase, RNA-binding, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase |
| Biological process | Antiviral defense, Host-virus interaction, Immunity, Innate immunity, Transcription, Transcription regulation |
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. 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. 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). 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. 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 proteasomal 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 pro-inflammatory 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. 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).
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.