EIF2AK1

EIF2AK1
Identifiers
Aliases	EIF2AK1, HCR, HRI, eukaryotic translation initiation factor 2 alpha kinase 1
External IDs	MGI: 1353448 HomoloGene: 8290 GeneCards: EIF2AK1
Gene ontology Molecular function • transferase activity • nucleotide binding • protein kinase activity • kinase activity • protein serine/threonine kinase activity • ATP binding • heme binding • protein homodimerization activity • eukaryotic translation initiation factor 2alpha kinase activity • translation initiation factor activity Cellular component • cytoplasm Biological process • negative regulation of translation • phosphorylation • regulation of hemoglobin biosynthetic process • response to stress • iron ion homeostasis • macrophage differentiation • protein phosphorylation • regulation of translational initiation by eIF2 alpha phosphorylation • acute inflammatory response • protoporphyrinogen IX metabolic process • regulation of eIF2 alpha phosphorylation by heme • response to external stimulus • phagocytosis • negative regulation of translational initiation by iron • regulation of translation • negative regulation of cell proliferation • protein autophosphorylation • negative regulation of hemoglobin biosynthetic process • translational initiation Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	27102	15467
Ensembl	ENSG00000086232	ENSMUSG00000029613
UniProt	Q9BQI3	Q9Z2R9
RefSeq (mRNA)	NM_014413 NM_001134335	NM_013557
RefSeq (protein)	NP_001127807 NP_055228 NP_055228.2	NP_038585
Location (UCSC)	Chr 7: 6.02 – 6.06 Mb	Chr 5: 143.82 – 143.9 Mb
PubMed search	[1]	[2]
Wikidata
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Eukaryotic translation initiation factor 2-alpha kinase 1 is an enzyme that in humans is encoded by the EIF2AK1 gene.^[3][4][5]

FUNCTION: It 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.

Catalytic activity: ATP + a protein = ADP + a phosphoprotein

Enzyme regulation: Induced by acute heme depletion, that not only increases EIF2AK1 protein levels, but also stimulates kinase activity by autophosphorylation. Inhibited by the heme-degradation products biliverdin and bilirubin. Induced by oxidative stress generated by arsenite treatment. 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.

cite:http://www.uniprot.org/uniprot/Q9BQI3 The HRI gene is localized to 7p22 where its 3' end slightly overlaps the 3' end of the gene JTV1. The two genes are transcribed from opposite strands. Studies in rat and rabbit suggest that the HRI gene product phosphorylates the alpha subunit of eukaryotic initiation factor 2. Its kinase activity is induced by low levels of heme and inhibited by the presence of heme.^[5]

References

Further reading