EIF2AK1
Identifiers
AliasesEIF2AK1, HCR, HRI, eukaryotic translation initiation factor 2 alpha kinase 1, LEMSPAD, hHRI
External IDsOMIM: 613635 MGI: 1353448 HomoloGene: 8290 GeneCards: EIF2AK1
Orthologs
SpeciesHumanMouse
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 MbChr 5: 143.8 – 143.84 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Eukaryotic translation initiation factor 2-alpha kinase 1 is an enzyme that in humans is encoded by the EIF2AK1 gene.[5][6][7]

Function

EIF2AK1 inhibits protein synthesis at the translation initiation level, in response to various stress conditions, including oxidative stress, heme deficiency, osmotic shock and heat shock. EIF2AK1 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. Owing to this unique heme-sensing capacity, it plays a crucial role in shutting off protein synthesis during acute heme-deficient conditions. In red blood cells (RBCs), it controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of the heme and globin moieties of hemoglobin. Thus plays an essential protective role for RBC survival in anemias of iron deficiency. EIF2AK1 also act to moderate ER stress during acute heme-deficient conditions.

Enzymology

EIF2AK1 is a kinase, thus it catalyses the following reaction:

ATP + a protein = ADP + a phosphoprotein

EIF2AK1 is 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:https://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.[7]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000086232 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000029613 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Chen JJ, London IM (May 1995). "Regulation of protein synthesis by heme-regulated eIF-2 alpha kinase". Trends Biochem Sci. 20 (3): 105–8. doi:10.1016/S0968-0004(00)88975-6. PMID 7709427.
  6. ↑ Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O (Apr 2000). "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (1): 65–73. doi:10.1093/dnares/7.1.65. PMID 10718198.
  7. 1 2 "Entrez Gene: EIF2AK1 eukaryotic translation initiation factor 2-alpha kinase 1".

Further reading


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