EIF2AK1 — Eukaryotic translation initiation factor 2 alpha kinase 1
EIF2AK1 belongs to a gene co-expression module in 4 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.
EIF2AK1's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| CD4⁺ T cells | Oxidative phosphorylation Mitochondrial & OxPhos | ACADVL, CHMP1A, COX14, EML2, ETFA, GPR108, NDUFA8, PARP1 +12 more | View in SCUBA |
| Gamma-delta T cells | mRNA Splicing RNA processing & translation | ARHGDIA, DDX27, DDX59, EWSR1, FBXL5, GNL1, GTF2F1, HNRNPM +14 more | |
| Hematopoietic progenitor cells | Replication Stress Response Cell cycle | CENPU, DNAJC9, HLTF, MRPL52, PIP4K2A, POLE2, SLC12A6, TLN1 +2 more | |
| Macrophages | ER Morphology Stress Stress | ARMC1, ARPP19, ATL3, CMPK1, CYB5B, ELAVL1, ERGIC2, HDAC2 +8 more | View in SCUBA |
About the gene
| Synonyms | HCR, hHRI, HRI, KIAA1369 |
|---|---|
| Chromosome | 7: 6022247-6059175 |
| 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, Protein synthesis inhibitor, Serine/threonine-protein kinase, Transferase |
Function
Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress conditions. Key activator of the integrated stress response (ISR) required for adaptation to various stress, such as heme deficiency, oxidative stress, osmotic shock, mitochondrial dysfunction and heat shock. EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming. Acts as a key sensor of heme-deficiency: in normal conditions, binds hemin via a cysteine thiolate and histidine nitrogenous coordination, leading to inhibit the protein kinase activity (By similarity). This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell: heme depletion relieves inhibition and stimulates kinase activity, activating the ISR (By similarity). Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions (By similarity). In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties (By similarity). It thereby plays an essential protective role for RBC survival in anemias of iron deficiency (By similarity). Iron deficiency also triggers activation by full-length DELE1. Also activates the ISR in response to mitochondrial dys HRI/EIF2AK1 protein kinase activity is activated upon binding to the processed form of DELE1 (S-DELE1), thereby promoting the ATF4-mediated reprogramming. Also acts as an activator of mitophagy in response to mitochondrial damage: catalyzes phosphorylation of eIF-2-alpha (EIF2S1) following activation by S-DELE1, thereby promoting mitochondrial localization of EIF2S1, triggering PRKN-independent mitophagy.
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.