EIF2AK1

Eukaryotic translation initiation factor 2-alpha kinase 1
Identifiers
Symbols	EIF2AK1 ; HCR; HRI
External IDs	OMIM: 613635 MGI: 1353448 HomoloGene: 8290 IUPHAR: 2015 ChEMBL: 6029 GeneCards: EIF2AK1 Gene
EC number	2.7.11.1
Gene ontology Molecular function • eukaryotic translation initiation factor 2alpha kinase activity • ATP binding • heme binding • protein homodimerization activity Cellular component • cytoplasm Biological process • acute inflammatory response • phagocytosis • response to stress • negative regulation of cell proliferation • response to external stimulus • regulation of translational initiation by eIF2 alpha phosphorylation • regulation of eIF2 alpha phosphorylation by heme • macrophage differentiation • negative regulation of translational initiation by iron • protoporphyrinogen IX metabolic process • protein autophosphorylation • negative regulation of hemoglobin biosynthetic process • iron ion homeostasis 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_001134335	NM_013557
RefSeq (protein)	NP_001127807	NP_038585
Location (UCSC)	Chr 7: 6.02 – 6.06 Mb	Chr 5: 143.82 – 143.9 Mb
PubMed search

Eukaryotic translation initiation factor 2-alpha kinase 1 is an enzyme that in humans is encoded by the EIF2AK1 gene.^[1][2][3]

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.^[3]

References

1. 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.
2. 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.
3. "Entrez Gene: EIF2AK1 eukaryotic translation initiation factor 2-alpha kinase 1".

Further reading

• Hu RM, Han ZG, Song HD; et al. (2000). "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning.". Proc. Natl. Acad. Sci. U.S.A. 97 (17): 9543–8. doi:10.1073/pnas.160270997. PMC 16901. PMID 10931946.
• Shao J, Grammatikakis N, Scroggins BT; et al. (2001). "Hsp90 regulates p50(cdc37) function during the biogenesis of the activeconformation of the heme-regulated eIF2 alpha kinase.". J. Biol. Chem. 276 (1): 206–14. doi:10.1074/jbc.M007583200. PMID 11036079.
• Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination.". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Hwang SY, Kim MK, Kim JC (2001). "Cloning of hHRI, human heme-regulated eukaryotic initiation factor 2alpha kinase: down-regulated in epithelial ovarian cancers.". Mol. Cells 10 (5): 584–91. doi:10.1007/s10059-000-0584-5. PMID 11101152.
• Wiemann S, Weil B, Wellenreuther R; et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
• Simpson JC, Wellenreuther R, Poustka A; et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing.". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
• Anand S, Pal JK (2003). "The haem-regulated eukaryotic initiation factor 2alpha kinase: a molecular indicator of lead-toxicity anaemia in rabbits.". Biotechnol. Appl. Biochem. 36 (Pt 1): 57–62. doi:10.1042/BA20020009. PMID 12149123.
• Omasa T, Chen YG, Mantalaris A; et al. (2003). "Molecular cloning and sequencing of the human heme-regulated eukaryotic initiation factor 2 alpha (eIF-2 alpha) kinase from bone marrow culture.". DNA Seq. 13 (3): 133–7. doi:10.1080/10425170290023428. PMID 12391722.
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Scherer SW, Cheung J, MacDonald JR; et al. (2003). "Human chromosome 7: DNA sequence and biology.". Science 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205.
• Rafie-Kolpin M, Han AP, Chen JJ (2003). "Autophosphorylation of threonine 485 in the activation loop is essential for attaining eIF2alpha kinase activity of HRI.". Biochemistry 42 (21): 6536–44. doi:10.1021/bi034005v. PMID 12767237.
• Hillier LW, Fulton RS, Fulton LA; et al. (2003). "The DNA sequence of human chromosome 7.". Nature 424 (6945): 157–64. doi:10.1038/nature01782. PMID 12853948.
• Ota T, Suzuki Y, Nishikawa T; et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Wiemann S, Arlt D, Huber W; et al. (2004). "From ORFeome to biology: a functional genomics pipeline.". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
• Mehrle A, Rosenfelder H, Schupp I; et al. (2006). "The LIFEdb database in 2006.". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
• Olsen JV, Blagoev B, Gnad F; et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.". Cell 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.