|Other Names||Eukaryotic translation initiation factor 2-alpha kinase 1, Heme-controlled repressor, HCR, Heme-regulated eukaryotic initiation factor eIF-2-alpha kinase, Heme-regulated inhibitor, Hemin-sensitive initiation factor 2-alpha kinase, EIF2AK1, HRI, KIAA1369|
|Target/Specificity||The synthetic peptide sequence used to generate the antibody AP8114b was selected from the C-term region of human EIF2AK1. A 10 to 100 fold molar excess to antibody is recommended. Precise conditions should be optimized for a particular assay.|
|Format||Synthetic peptide was lyophilized with 100% acetonitrile and is supplied as a powder. Reconstitute with 0.1 ml DI water for a final concentration of 1 mg/ml.|
|Storage||Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C.|
|Precautions||This product is for research use only. Not for use in diagnostic or therapeutic procedures.|
|Function||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 (By similarity).|
|Tissue Location||Expressed predominantly in erythroid cells. At much lower levels, expressed in hepatocytes (at protein level)|
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Provided below are standard protocols that you may find useful for product applications.
Eukaryotic translation initiation factor 2-alpha kinase 1 (EIF2AK1) belongs to the protein kinase superfamily, Ser/Thr protein kinase family, GCN2 subfamily. It mediates down-regulation of protein synthesis in response to various stress conditions by the phosphorylation of EIF2S1 at Ser-48 and Ser-51. Hemin inactivates EIF2AK1 by promoting the formation of a disulfide-linked homodimer. The homodimer is non-covalently bound in the absence of hemin, and converted to an inactive disulfide linked homodimer in the presence of hemin. Binding of nitric oxide (NO) to the heme iron in the N-terminal heme-binding domain activates the kinase activity, while binding of carbon monoxide (CO) suppresses kinase activity. EIF2AK1 is activated by autophosphorylation; phosphorylated predominantly on serine and threonine residues, but also on tyrosine residues.
Hwang S.-Y., Mol. Cells 10:584-591(2000).Omasa T., DNA Seq. 13:133-137(2002).
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