Aliases for EIF2AK1 Gene
- Eukaryotic Translation Initiation Factor 2 Alpha Kinase 1 2 3 5
- HRI 2 3 4
- Heme-Regulated Eukaryotic Initiation Factor EIF-2-Alpha Kinase 3 4
- Eukaryotic Translation Initiation Factor 2-Alpha Kinase 1 3 4
- Hemin-Sensitive Initiation Factor 2-Alpha Kinase 3 4
- Heme Regulated Initiation Factor 2 Alpha Kinase 2 3
- Heme-Controlled Repressor 3 4
- Heme-Regulated Inhibitor 3 4
External Ids for EIF2AK1 Gene
Previous GeneCards Identifiers for EIF2AK1 Gene
The protein encoded by this gene acts at the level of translation initiation to downregulate protein synthesis in response to stress. The encoded protein is a kinase that can be inactivated by hemin. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
GeneCards Summary for EIF2AK1 Gene
EIF2AK1 (Eukaryotic Translation Initiation Factor 2 Alpha Kinase 1) is a Protein Coding gene. Diseases associated with EIF2AK1 include Leukoencephalopathy, Motor Delay, Spasticity, And Dysarthria Syndrome and Pyriform Sinus Cancer. Among its related pathways are Toll-like Receptor Signaling Pathway and Regulation of lipid metabolism Insulin signaling-generic cascades. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is EIF2AK4.
UniProtKB/Swiss-Prot Summary for EIF2AK1 Gene
Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress conditions (PubMed:32132706, PubMed:32132707). Key activator of the integrated stress response (ISR) required for adaptation to various stress, such as heme deficiency, oxidative stress, osmotic shock, mitochondrial dysfunction and heat shock (PubMed:32132706, PubMed:32132707). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707). Acts as a key sensor of heme-deficiency: in normal conditions, binds hemin via a cysteine thiolate and histidine nitrogenous coordination, leading to inhibit the protein kinase activity (By similarity). This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell: heme depletion relieves inhibition and stimulates kinase activity, activating the ISR (By similarity). Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions (By similarity). In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties (By similarity). It thereby plays an essential protective role for RBC survival in anemias of iron deficiency (By similarity). Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes (By similarity). May also regulate endoplasmic reticulum (ER) stress during acute heme-deficient conditions (By similarity). Also activates the ISR in response to mitochondrial dysfunction: HRI/EIF2AK1 protein kinase activity is activated upon binding to the processed form of DELE1 (S-DELE1), thereby promoting the ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707).