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.
Protein type: EC; Kinase, protein; Other group; PEK family; Protein kinase, Other; Protein kinase, Ser/Thr (non-receptor); Translation
Chromosomal Location of Human Ortholog: 12p11
Cellular Component:  cytoplasm
Molecular Function:  ATP binding; eukaryotic translation initiation factor 2alpha kinase activity; heme binding; protein homodimerization activity; protein kinase activity
Biological Process:  acute inflammatory response; iron ion homeostasis; macrophage differentiation; negative regulation of cell proliferation; negative regulation of hemoglobin biosynthetic process; negative regulation of translation; phagocytosis; protein autophosphorylation; protein phosphorylation; protoporphyrinogen IX metabolic process; regulation of eIF2 alpha phosphorylation by heme; regulation of hemoglobin biosynthetic process; regulation of translation; regulation of translational initiation by eIF2 alpha phosphorylation; response to iron ion starvation
Reference #:  Q63185 (UniProtKB)
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; hemin-sensitive initiation factor 2a kinase; Hri
Gene Symbols: Eif2ak1
Molecular weight: 69,586 Da
Basal Isoelectric point: 5.61  Predict pI for various phosphorylation states
CST Pathways:  Translation: eIF2
Select Structure to View Below


Protein Structure Not Found.

Cross-references to other databases:  STRING  |  BioGPS  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene