EIF2AK1 - Eukaryotic translation initiation factor 2-alpha kinase 1 - human protein (Function)
 
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EIF2AK1 »  Eukaryotic translation initiation factor 2-alpha kinase 1   [ EC 2.7.11.1 ]
 
Protein also known as:  Heme-regulated eukaryotic initiation factor eIF-2-alpha kinase.
Gene name:  EIF2AK1
Entry whose protein(s) existence is based on evidence at protein level
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1 34 2
GENE REF ISO

Function

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Overview 
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).  
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Eukaryotic translation initiation factor 2alpha kinase activitydefinition[GO:0004694]  
1
  • IDAUniProtKB
Heme bindingdefinition[GO:0020037]  
  • ISSOrtholog Curator
Protein homodimerization activitydefinition[GO:0042803]  
  • ISSOrtholog Curator
GO biological process 
Negative regulation of cell proliferationdefinition[GO:0008285] silver  
  • IEAOrtholog Compara
Negative regulation of hemoglobin biosynthetic processdefinition[GO:0046986]  
  • ISSOrtholog Curator
Negative regulation of translational initiation by irondefinition[GO:0045993]  
1
  • NASUniProtKB
Protein autophosphorylationdefinition[GO:0046777]  
  • ISSOrtholog Curator
Protoporphyrinogen IX metabolic processdefinition[GO:0046501] silver  
  • IEAOrtholog Compara
Regulation of eIF2 alpha phosphorylation by hemedefinition[GO:0010999] silver  
  • IEAOrtholog Compara
Response to external stimulusdefinition[GO:0009605]  
1
  • IEPUniProtKB
Response to stressdefinition[GO:0006950]  
1
  • IEPUniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It is regulated in the following manner
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 (By similarity).  
  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Hepatitis C  hsa05160+27102  
Herpes simplex infection  hsa05168+27102  
Influenza A  hsa05164+27102  
Measles  hsa05162+27102  
Protein processing in endoplasmic reticulum  hsa04141+27102  
 

Keywords

Molecular function 
Kinase  definition   [KW-0418]
Protein synthesis inhibitor  definition   [KW-0652]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: EIF2AK1
GenomeRNAi: 27102
PRO: PR:Q9BQI3
Chemistry
GuidetoPHARMACOLOGY: 2015