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HRI
Inhibits protein synthesis at the translation initiation level, in response to various stress conditions, including oxidative stress, heme deficiency, osmotic shock and heat shock. Exerts its function through the phosphorylation of EIF2S1 at 'Ser-48' and 'Ser-51', thus preventing its recycling. Binds hemin forming a 1:1 complex through a cysteine thiolate and histidine nitrogenous coordination. This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell. Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions. In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties. Thus plays an essential protective role for RBC survival in anemias of iron deficiency. Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes. May also contain ER stress during acute heme-deficient conditions. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily. Expressed predominantly in erythroid cells. At much lower levels, expressed in hepatocytes (at protein level). 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
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| Protein type: EC 2.7.11.1; HRI subfamily; Kinase, protein; Other group; PEK family; Protein kinase, Other; Protein kinase, Ser/Thr (non-receptor); Translation |
| Chromosomal Location of mouse Ortholog: 5|5 G2 |
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Cellular Component:
cytoplasm; cytosol; nucleus
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Molecular Function:
ATP binding; eukaryotic translation initiation factor 2alpha kinase activity; heme binding; kinase activity; nucleotide binding; protein binding; protein homodimerization activity; protein kinase activity; protein serine/threonine kinase activity; transferase activity
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Biological Process:
acute inflammatory response; establishment of localization in cell; HRI-mediated signaling; integrated stress response signaling; macrophage differentiation; multicellular organismal-level iron ion homeostasis; negative regulation of cell population proliferation; negative regulation of hemoglobin biosynthetic process; negative regulation of translation; phagocytosis; phosphorylation; protein autophosphorylation; protein phosphorylation; protoporphyrinogen IX metabolic process; regulation of eIF2 alpha phosphorylation by heme; regulation of hemoglobin biosynthetic process; regulation of translation; response to iron ion starvation
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Reference #:
Q9Z2R9
(UniProtKB)
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Alt. Names/Synonyms: E2AK1; Eif2ak1; eukaryotic translation initiation factor 2 alpha kinase 1; Eukaryotic translation initiation factor 2-alpha kinase 1; HCR; Heme-controlled repressor; Heme-regulated eukaryotic initiation factor eIF-2-alpha kinase; Heme-regulated inhibitor; Hemin-sensitive initiation factor 2-alpha kinase; Hri; MGC118066
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Gene Symbols: Eif2ak1
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Molecular weight:
69,702 Da
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Basal Isoelectric point:
5.68
Predict pI for various phosphorylation states
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CST Pathways:
Translation: eIF2
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