バックグラウンド: | 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). |
シノニム: | Eukaryotic translation initiation factor 2-α kinase 1 (EC 2.7.11.1) (Heme-controlled repressor) (HCR) (Heme-regulated eukaryotic initiation factor eIF-2-α kinase) (Heme-regulated inhibitor) (Hemin-sensitive initiation factor 2-α kinase), EIF2AK1, HRI KIAA1369 |
UniProt Protein Function: | HRI: a protein kinase of the PEK family. Phosphorylates the alpha subunit of eukaryotic initiation factor 2 in response to various stress conditions, inhibiting protein synthesis at the level of initiation. Its kinase activity is induced by low levels of heme and inhibited by the presence of heme. 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. Requires association with a multiprotein complex containing Hsp90, CDC37 and PPP5C for maturation and activation by autophosporylation. Two alternatively spliced isoforms have been described. |
UniProt Protein Details: | Protein type:Translation; Protein kinase, Ser/Thr (non-receptor); Protein kinase, Other; EC 2.7.11.1; Kinase, protein; Other group; PEK family Chromosomal Location of Human Ortholog: 7p22 Cellular Component: cytoplasm Molecular Function:protein homodimerization activity; heme binding; ATP binding; eukaryotic translation initiation factor 2alpha kinase activity Biological Process: response to external stimulus; negative regulation of cell proliferation; negative regulation of translational initiation by iron; protoporphyrinogen IX metabolic process; protein amino acid autophosphorylation; response to stress; negative regulation of hemoglobin biosynthetic process |
NCBI Summary: | 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] |
UniProt Code: | Q9BQI3 |
NCBI GenInfo Identifier: | 32172458 |
NCBI Gene ID: | 27102 |
NCBI Accession: | Q9BQI3.2 |
UniProt Secondary Accession: | Q9BQI3,Q549K6, Q8NBW3, Q9HC02, Q9NYE0, Q9P0V6, Q9P1J5 Q9P2H8, Q9UHG4, A8K2R2, |
UniProt Related Accession: | Q9BQI3 |
Molecular Weight: | |
NCBI Full Name: | Eukaryotic translation initiation factor 2-alpha kinase 1 |
NCBI Synonym Full Names: | eukaryotic translation initiation factor 2-alpha kinase 1 |
NCBI Official Symbol: | EIF2AK1 |
NCBI Official Synonym Symbols: | HCR; HRI |
NCBI Protein Information: | eukaryotic translation initiation factor 2-alpha kinase 1; heme-regulated inhibitor; heme-regulated repressor; heme-controlled repressor; heme sensitive initiation factor 2a kinase; heme regulated initiation factor 2 alpha kinase; heme-regulated initiation factor 2-alpha kinase; hemin-sensitive initiation factor 2-alpha kinase; heme-regulated eukaryotic initiation factor eIF-2-alpha kinase |
UniProt Protein Name: | Eukaryotic translation initiation factor 2-alpha kinase 1 |
UniProt Synonym Protein Names: | Heme-controlled repressor; HCR; Heme-regulated eukaryotic initiation factor eIF-2-alpha kinase; Heme-regulated inhibitor; Hemin-sensitive initiation factor 2-alpha kinase |
Protein Family: | Eukaryotic translation initiation factor 2-alpha kinase |
UniProt Gene Name: | EIF2AK1 |
UniProt Entry Name: | E2AK1_HUMAN |