GeneID: 264



Names

Common Name: EIF2AK1 Type: Gene
Chromosome: 7 (NC_000007.14) Locus: NM_014413.4 (EIF2AK1)
HUGO Symbol: EIF2AK1 Full Name: eukaryotic translation initiation factor 2 alpha kinase 1
Exons: 15 Introns: 14

Description:
The protein encoded by this gene acts at the level of translation initiation to downregulate protein synthesis in response to conditions of stress, such as heme deficiency, oxidative stress, heat shock and osmotic shock. It exerts its function through the phosphorylation of EIF2S1, thus preventing its recycling. The encoded protein is a heme-regulated eIF2α kinase (HRI). Two transcript variants encoding different isoforms have been found for this gene. In the setting of heme deficiency, HRI is activated to attenuate globin translation in red blood cell (RBC) precursors in order to ensure no globin is translated in excess of the heme available for the assembly of stable haemoglobin. HRI is essential not only for the translational regulation of globins, but also for the survival of RBC precursors in iron deficiency. Moreover, HRI is activated in the RBCs of β-thalassaemic mice to minimize protein synthesis, including that of unpaired α-globins. In HRI-deficient β-thalassaemic mice, protein synthesis continues and a large excess of α-globin is made, forming inclusions that destroy the RBC precursors. HRI is acts as a modifier of pathologic α-globin production in β-thalassemia, dampening the severity of the disease. Protein domain-focused CRISPR-Cas screening in HUDEP-2 cells identified HRI as a potential HbF repressor. In addition, BCL11A appears to serve as an HRI target in the control of HbF production in human adult erythroid cells. HRI provides a potential therapeutic target for haemoglobinopathies.

Synonyms: HRI , KIAA1369 , HCR

Comments:
N/A

Sequence Viewer

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Publications / Origin

  1. Han AP, Fleming MD, Chen JJ, Heme-regulated eIF2alpha kinase modifies the phenotypic severity of murine models of erythropoietic protoporphyria and beta-thalassemia., J. Clin. Invest., 115(6), 1562-70, 2005 PubMed
  2. Chen JJ, Regulation of protein synthesis by the heme-regulated eIF2alpha kinase: relevance to anemias., Blood, 109(7), 2693-9, 2007 PubMed
  3. Chen JJ, Translational control by heme-regulated eIF2α kinase during erythropoiesis., Curr. Opin. Hematol., 21(3), 172-8, 2014 PubMed
  4. Grevet JD, Lan X, Hamagami N, Edwards CR, Sankaranarayanan L, Ji X, Bhardwaj SK, Face CJ, Posocco DF, Abdulmalik O, Keller CA, Giardine B, Sidoli S, Garcia BA, Chou ST, Liebhaber SA, Hardison RC, Shi J, Blobel GA, Domain-focused CRISPR screen identifies HRI as a fetal hemoglobin regulator in human erythroid cells., Science, 361(6399), 285-290, 2018 PubMed
Created on 2019-07-02 13:14:11, Last reviewed on (Show full history)


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