EIF2AK1(HRI);

Eukaryotic translation initiation factor 2-alpha kinase 1;

Heme-regulated eukaryotic initiation factor eIF-2-alpha kinase;Heme-controlled repressor(HCR);Hemin-sensitive initiation factor 2-alpha kinase;Heme-regulated inhibitor;

Rabbit (Oryctolagus cuniculus). 

Synthesized in an inactive form that binds to the N-terminal domain of CDC37. Has to be associated with a multiprotein complex containing Hsp90, CDC37 and PPP5C for maturation and activation by autophosphorylation. The phosphatase PPP5C modulates this activation (By similarity). Forms oligomers. Has been reported as a homodimer, as well as a hexamer in the absence of hemin (By similarity). Converted to an inactive disulfide linked homodimer in the presence of hemin.

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 (By similarity). May also contain ER stress during acute heme-deficient conditions.

Cytoplasm

626

N/A

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9986.ENSOCUP00000010856

Ocu.1869

P33279

PF00069