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Aliases for EIF2AK1 Gene

Aliases for EIF2AK1 Gene

  • Eukaryotic Translation Initiation Factor 2-Alpha Kinase 1 2 3
  • HRI 3 4 6
  • Heme-Regulated Eukaryotic Initiation Factor EIF-2-Alpha Kinase 3 4
  • Hemin-Sensitive Initiation Factor 2-Alpha Kinase 3 4
  • Heme Regulated Initiation Factor 2 Alpha Kinase 2 3
  • Heme-Controlled Repressor 3 4
  • Heme-Regulated Inhibitor 3 4
  • EC 2.7.11.1 4 64
  • HCR 3 4
  • Heme-Regulated Initiation Factor 2-Alpha Kinase 3
  • Heme Sensitive Initiation Factor 2a Kinase 3
  • Heme-Regulated Repressor 3
  • EC 2.7.11 64
  • KIAA1369 4

External Ids for EIF2AK1 Gene

Summaries for EIF2AK1 Gene

Entrez Gene Summary for EIF2AK1 Gene

  • 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]

GeneCards Summary for EIF2AK1 Gene

EIF2AK1 (Eukaryotic Translation Initiation Factor 2-Alpha Kinase 1) is a Protein Coding gene. Among its related pathways are Apoptotic Pathways in Synovial Fibroblasts and Epstein-Barr virus infection. GO annotations related to this gene include protein homodimerization activity and eukaryotic translation initiation factor 2alpha kinase activity. An important paralog of this gene is EIF2AK4.

UniProtKB/Swiss-Prot for EIF2AK1 Gene

  • 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).

Gene Wiki entry for EIF2AK1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for EIF2AK1 Gene

Genomics for EIF2AK1 Gene

Genomic Location for EIF2AK1 Gene

Start:
6,022,244 bp from pter
End:
6,059,230 bp from pter
Size:
36,987 bases
Orientation:
Minus strand

Genomic View for EIF2AK1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for EIF2AK1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EIF2AK1 Gene

Regulatory Elements for EIF2AK1 Gene

Proteins for EIF2AK1 Gene

  • Protein details for EIF2AK1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BQI3-E2AK1_HUMAN
    Recommended name:
    Eukaryotic translation initiation factor 2-alpha kinase 1
    Protein Accession:
    Q9BQI3
    Secondary Accessions:
    • A8K2R2
    • Q549K6
    • Q8NBW3
    • Q9HC02
    • Q9NYE0
    • Q9P0V6
    • Q9P1J5
    • Q9P2H8
    • Q9UHG4

    Protein attributes for EIF2AK1 Gene

    Size:
    630 amino acids
    Molecular mass:
    71106 Da
    Quaternary structure:
    • Synthesized in an inactive form that binds to the N-terminal domain of CDC37. Has to be associated with a multiprotein complex containing Hsp90, CDC37 and PPP5C for maturation and activation by autophosphorylation. The phosphatase PPP5C modulates this activation. Forms oligomers. Has been reported as a non-covalently bound homodimer, as well as a hexamer in the absence of hemin. Converted to an inactive disulfide linked homodimer in the presence of hemin (By similarity).
    Miscellaneous:
    • Can bind 1 molecules of heme per polypeptide chain.
    SequenceCaution:
    • Sequence=AAF70289.1; Type=Frameshift; Positions=24, 26, 33; Evidence={ECO:0000305}; Sequence=AAF71057.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAA92607.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Alternative splice isoforms for EIF2AK1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for EIF2AK1 Gene

Proteomics data for EIF2AK1 Gene at MOPED

Post-translational modifications for EIF2AK1 Gene

  • Activated by autophosphorylation; phosphorylated predominantly on serine and threonine residues, but also on tyrosine residues. Autophosphorylation at Thr-488 is required for kinase activation. The active autophosphorylated form apparently is largely refractory to cellular heme fluctuations (By similarity).
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys472

Other Protein References for EIF2AK1 Gene

Domains for EIF2AK1 Gene

Protein Domains for EIF2AK1 Gene

UniProtKB/Swiss-Prot:

E2AK1_HUMAN
Domain:
  • Contains 1 protein kinase domain.:
    • Q9BQI3
Family:
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.:
    • Q9BQI3
Similarity:
  • Contains 2 HRM (heme regulatory motif) repeats.:
    • Q9BQI3
genes like me logo Genes that share domains with EIF2AK1: view

Function for EIF2AK1 Gene

Molecular function for EIF2AK1 Gene

UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein
UniProtKB/Swiss-Prot EnzymeRegulation: 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).
UniProtKB/Swiss-Prot Function: 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).

Enzyme Numbers (IUBMB) for EIF2AK1 Gene

Gene Ontology (GO) - Molecular Function for EIF2AK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity --
GO:0004694 eukaryotic translation initiation factor 2alpha kinase activity IDA 11036079
GO:0004713 protein tyrosine kinase activity --
GO:0005515 protein binding --
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with EIF2AK1: view
genes like me logo Genes that share phenotypes with EIF2AK1: view

Animal Models for EIF2AK1 Gene

MGI Knock Outs for EIF2AK1:

No data available for Transcription Factor Targeting and HOMER Transcription for EIF2AK1 Gene

Localization for EIF2AK1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for EIF2AK1 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for EIF2AK1 Gene COMPARTMENTS Subcellular localization image for EIF2AK1 gene
Compartment Confidence
cytosol 2
endoplasmic reticulum 2
nucleus 2

Gene Ontology (GO) - Cellular Components for EIF2AK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with EIF2AK1: view

Pathways for EIF2AK1 Gene

genes like me logo Genes that share pathways with EIF2AK1: view

Pathways by source for EIF2AK1 Gene

1 GeneGo (Thomson Reuters Life Sciences Research) pathway for EIF2AK1 Gene
1 Qiagen pathway for EIF2AK1 Gene

Gene Ontology (GO) - Biological Process for EIF2AK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006417 regulation of translation --
GO:0006468 protein phosphorylation --
GO:0006950 response to stress IEP 11036079
GO:0008285 negative regulation of cell proliferation IEA --
GO:0009605 response to external stimulus IEP 11036079
genes like me logo Genes that share ontologies with EIF2AK1: view

Compounds for EIF2AK1 Gene

(6) HMDB Compounds for EIF2AK1 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0
Carbon monoxide
  • Carbon monoxide
124-38-9
Heme
  • (protoporphyrinato)iron
14875-96-8
Hemin
  • Chloro(protoporphyrinato)iron
16009-13-5

(5) Novoseek inferred chemical compound relationships for EIF2AK1 Gene

Compound -log(P) Hits PubMed IDs
arsenite 46.5 1
alanine 13.4 2
threonine 11.3 1
nitric oxide 0 7
tyrosine 0 1
genes like me logo Genes that share compounds with EIF2AK1: view

Transcripts for EIF2AK1 Gene

Unigene Clusters for EIF2AK1 Gene

Eukaryotic translation initiation factor 2-alpha kinase 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for EIF2AK1 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3a · 3b ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13a · 13b ^ 14a · 14b ^ 15 ^ 16a · 16b ^
SP1: - -
SP2: - -
SP3: -
SP4: -
SP5: - -
SP6: - - -
SP7: - -
SP8: - - - -
SP9: - -
SP10: - - - -
SP11: -
SP12:
SP13:

ExUns: 17a · 17b ^ 18a · 18b
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:

Relevant External Links for EIF2AK1 Gene

GeneLoc Exon Structure for
EIF2AK1
ECgene alternative splicing isoforms for
EIF2AK1

Expression for EIF2AK1 Gene

mRNA expression in normal human tissues for EIF2AK1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for EIF2AK1 Gene

SOURCE GeneReport for Unigene cluster for EIF2AK1 Gene Hs.520205

mRNA Expression by UniProt/SwissProt for EIF2AK1 Gene

Q9BQI3-E2AK1_HUMAN
Tissue specificity: Expressed predominantly in erythroid cells. At much lower levels, expressed in hepatocytes (at protein level).
genes like me logo Genes that share expressions with EIF2AK1: view

Orthologs for EIF2AK1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for EIF2AK1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia EIF2AK1 36
  • 99.31 (n)
  • 98.89 (a)
EIF2AK1 37
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia EIF2AK1 36
  • 84 (n)
  • 81.5 (a)
EIF2AK1 37
  • 81 (a)
OneToOne
dog
(Canis familiaris)
Mammalia EIF2AK1 36
  • 87.06 (n)
  • 84.19 (a)
EIF2AK1 37
  • 83 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Eif2ak1 36
  • 83.44 (n)
  • 83.33 (a)
Eif2ak1 16
Eif2ak1 37
  • 83 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia EIF2AK1 37
  • 68 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia EIF2AK1 37
  • 59 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Eif2ak1 36
  • 82.18 (n)
  • 82.39 (a)
chicken
(Gallus gallus)
Aves EIF2AK1 36
  • 63.1 (n)
  • 55.96 (a)
EIF2AK1 37
  • 52 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia EIF2AK1 37
  • 48 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia eif2ak1 36
  • 58.19 (n)
  • 51.41 (a)
zebrafish
(Danio rerio)
Actinopterygii eif2ak1 36
  • 54.79 (n)
  • 48.68 (a)
eif2ak1 37
  • 39 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea gcn-2 37
  • 8 (a)
ManyToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GCN2 37
  • 9 (a)
OneToMany
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes hri1 36
  • 45.79 (n)
  • 37.38 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 30 (a)
OneToOne
Species with no ortholog for EIF2AK1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for EIF2AK1 Gene

ENSEMBL:
Gene Tree for EIF2AK1 (if available)
TreeFam:
Gene Tree for EIF2AK1 (if available)

Paralogs for EIF2AK1 Gene

Paralogs for EIF2AK1 Gene

Selected SIMAP similar genes for EIF2AK1 Gene using alignment to 5 proteins:

Pseudogenes.org Pseudogenes for EIF2AK1 Gene

genes like me logo Genes that share paralogs with EIF2AK1: view

Variants for EIF2AK1 Gene

Sequence variations from dbSNP and Humsavar for EIF2AK1 Gene

SNP ID Clin Chr 07 pos Sequence Context AA Info Type MAF
rs2639 -- 6,026,830(+) TGCAC(C/T)GGACA reference, synonymous-codon
rs2640 - 6,026,819(+) TATAC(C/T)TGGCT reference, missense
rs475323 -- 6,050,969(-) AGAAA(C/T)GGCTT intron-variant
rs485254 -- 6,059,857(+) ccact(A/G)tactc upstream-variant-2KB
rs509228 -- 6,044,364(-) cctcc(C/T)gagta intron-variant

Structural Variations from Database of Genomic Variants (DGV) for EIF2AK1 Gene

Variant ID Type Subtype PubMed ID
nsv436904 CNV Insertion 17901297
nsv830894 CNV Loss 17160897
nsv7392 OTHER Inversion 18451855
esv1914954 OTHER Inversion 16254605
esv988101 CNV Deletion 20482838
esv1385792 CNV Deletion 17803354
esv2658842 CNV Deletion 23128226

Relevant External Links for EIF2AK1 Gene

HapMap Linkage Disequilibrium report
EIF2AK1

Disorders for EIF2AK1 Gene

(3) Novoseek inferred disease relationships for EIF2AK1 Gene

Disease -log(P) Hits PubMed IDs
protein deficiency 55.2 2
hepatitis c 0 1
cancer 0 1

Relevant External Links for EIF2AK1

Genetic Association Database (GAD)
EIF2AK1
Human Genome Epidemiology (HuGE) Navigator
EIF2AK1
genes like me logo Genes that share disorders with EIF2AK1: view

No data available for UniProtKB/Swiss-Prot for EIF2AK1 Gene

Publications for EIF2AK1 Gene

  1. Regulation of protein synthesis by heme-regulated eIF-2 alpha kinase. (PMID: 7709427) Chen J.J. … London I.M. (Trends Biochem. Sci. 1995) 2 3 23
  2. Hsp90 regulates p50(cdc37) function during the biogenesis of the active conformation of the heme-regulated eIF2 alpha kinase. (PMID: 11036079) Shao J. … Matts R.L. (J. Biol. Chem. 2001) 3 4 23
  3. Cloning of hHRI, human heme-regulated eukaryotic initiation factor 2alpha kinase: down-regulated in epithelial ovarian cancers. (PMID: 11101152) Hwang S.-Y. … Kim J.-C. (Mol. Cells 2000) 3 4 23
  4. 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. (PMID: 10718198) Nagase T. … Ohara O. (DNA Res. 2000) 2 3 4
  5. Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning. (PMID: 10931946) Hu R.-M. … Chen J.-L. (Proc. Natl. Acad. Sci. U.S.A. 2000) 3 4

Products for EIF2AK1 Gene

Sources for EIF2AK1 Gene

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