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EIF2S1 eukaryotic translation initiation factor 2 subunit alpha [ Homo sapiens (human) ]

Gene ID: 1965, updated on 10-Dec-2024

Summary

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Official Symbol
EIF2S1provided by HGNC
Official Full Name
eukaryotic translation initiation factor 2 subunit alphaprovided by HGNC
Primary source
HGNC:HGNC:3265
See related
Ensembl:ENSG00000134001 MIM:603907; AllianceGenome:HGNC:3265
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
EIF2; EIF-2; EIF2A; EIF-2A; EIF-2alpha
Summary
The translation initiation factor EIF2 catalyzes the first regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA to 40S ribosomal subunits. Binding occurs as a ternary complex of methionyl-tRNA, EIF2, and GTP. EIF2 is composed of 3 nonidentical subunits, the 36-kD EIF2-alpha subunit (EIF2S1), the 38-kD EIF2-beta subunit (EIF2S2; MIM 603908), and the 52-kD EIF2-gamma subunit (EIF2S3; MIM 300161). The rate of formation of the ternary complex is modulated by the phosphorylation state of EIF2-alpha (Ernst et al., 1987 [PubMed 2948954]).[supplied by OMIM, Feb 2010]
Annotation information
Note: EIF2A (Gene ID: 83939) and EIF2S1 (Gene ID: 1965) share the EIF2A symbol/alias in common. EIF2A is a widely used alternative name for eukaryotic translation initiation factor 2 subunit alpha (EIF2S1), which can be confused with the official symbol for eukaryotic translation initiation factor 2A (EIF2A). [05 Jul 2018]
Expression
Ubiquitous expression in testis (RPKM 19.0), esophagus (RPKM 15.6) and 25 other tissues See more
Orthologs
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Genomic context

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See EIF2S1 in Genome Data Viewer
Location:
14q23.3
Exon count:
8
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (67360328..67386516)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (61567453..61593639)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (67827045..67853233)

Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene gephyrin Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5855 Neighboring gene ReSE screen-validated silencer GRCh37_chr14:67723162-67723330 Neighboring gene MPRA-validated peak2181 silencer Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:67825632-67826418 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8578 Neighboring gene protein associated with LIN7 1, MAGUK p55 family member Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_36264 Neighboring gene Sharpr-MPRA regulatory region 12737 Neighboring gene GATA motif-containing MPRA enhancer 49 Neighboring gene ATPase H+ transporting V1 subunit D Neighboring gene pleckstrin 2 Neighboring gene microRNA 5694

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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Related articles in PubMed

  1. Eukaryotic initiation factor 2α phosphorylation mediates fetal hemoglobin induction through a post-transcriptional mechanism. Hahn CK, et al. Blood, 2013 Jul 25. PMID 23690448, Free PMC Article
  2. Expression and purification of the subunits of human translational initiation factor 2 (eIF2): phosphorylation of eIF2 alpha and beta. Suragani RN, et al. Protein Expr Purif, 2006 May. PMID 16289913
  3. Lead-induced upregulation of the heme-regulated eukaryotic initiation factor 2alpha kinase is compromised by hemin in human K562 cells. Sarkar A, et al. Biochim Biophys Acta, 2005 Dec 30. PMID 16500424
  4. Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2alpha phosphorylation. Mazroui R, et al. Mol Biol Cell, 2006 Oct. PMID 16870703, Free PMC Article
  5. Adeno-associated viruses can induce phosphorylation of eIF2alpha via PKR activation, which can be overcome by helper adenovirus type 5 virus-associated RNA. Nayak R, et al. J Virol, 2007 Nov. PMID 17715234, Free PMC Article

See all (399) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Unfolded protein response markers Grp78 and eIF2alpha are upregulated with increasing alpha-synuclein levels in Lewy body disease.
    Title: Unfolded protein response markers Grp78 and eIF2alpha are upregulated with increasing alpha-synuclein levels in Lewy body disease.
  2. MiR-3074-5p Regulates Trophoblasts Function via EIF2S1/GDF15 Pathway in Recurrent Miscarriage.
    Title: MiR-3074-5p Regulates Trophoblasts Function via EIF2S1/GDF15 Pathway in Recurrent Miscarriage.
  3. CHIP suppresses the proliferation and migration of A549 cells by mediating the ubiquitination of eIF2alpha and upregulation of tumor suppressor RBM5.
    Title: CHIP suppresses the proliferation and migration of A549 cells by mediating the ubiquitination of eIF2α and upregulation of tumor suppressor RBM5.
  4. Activation of BZW1 by CEBPB in macrophages promotes eIF2alpha phosphorylation-mediated metabolic reprogramming and endoplasmic reticulum stress in MRL/lpr lupus-prone mice.
    Title: Activation of BZW1 by CEBPB in macrophages promotes eIF2α phosphorylation-mediated metabolic reprogramming and endoplasmic reticulum stress in MRL/lpr lupus-prone mice.
  5. C9orf72 regulates the unfolded protein response and stress granule formation by interacting with eIF2alpha.
    Title: C9orf72 regulates the unfolded protein response and stress granule formation by interacting with eIF2α.
  6. Helicobacter pylori Targets in AGS Human Gastric Adenocarcinoma: In Situ Proteomic Profiling and Systematic Analysis.
    Title: Helicobacter pylori Targets in AGS Human Gastric Adenocarcinoma: In Situ Proteomic Profiling and Systematic Analysis.
  7. PERK-eIF2alpha-ERK1/2 axis drives mesenchymal-endothelial transition of cancer-associated fibroblasts in pancreatic cancer.
    Title: PERK-eIF2α-ERK1/2 axis drives mesenchymal-endothelial transition of cancer-associated fibroblasts in pancreatic cancer.
  8. Higher-order phosphatase-substrate contacts terminate the integrated stress response.
    Title: Higher-order phosphatase-substrate contacts terminate the integrated stress response.
  9. Activation of the eIF2alpha/ATF4 axis drives triple-negative breast cancer radioresistance by promoting glutathione biosynthesis.
    Title: Activation of the eIF2α/ATF4 axis drives triple-negative breast cancer radioresistance by promoting glutathione biosynthesis.
  10. Resveratrol synergizes with cisplatin in antineoplastic effects against AGS gastric cancer cells by inducing endoplasmic reticulum stressmediated apoptosis and G2/M phase arrest.
    Title: Resveratrol synergizes with cisplatin in antineoplastic effects against AGS gastric cancer cells by inducing endoplasmic reticulum stress‑mediated apoptosis and G2/M phase arrest.
Submit: New GeneRIF Correction See all GeneRIFs (161)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Pr55(Gag) gag HIV-1 Gag co-localizes with eIF-2alpha in human cells PubMed
Tat tat Exposure of human umbilical vein endothelial cells to HIV-1 Tat causes broad activation of the unfolded-protein response in ER with phosphorylation of PERK, eIF2alpha, and JNK and induction of Grp78/BiP PubMed
tat Neurons exposed to HIV-1 Tat induces calcium loss from the endoplasmic reticulum via ryanodine receptor (RyR) and increases the phosphorylated levels of PERK, eIF2a, and XBP1 PubMed
tat HIV-1 Tat competes with eukaryotic initiation factor 2, a well characterized substrate of PKR, for phosphorylation by activated PKR PubMed
tat Eukaryotic translation initiation factor 2 (eIF2) recognizes and binds the TAR secondary structure in HIV-1 RNA, suggesting a role in Tat transactivation of the viral LTR promoter PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables RNA binding HDA PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ribosome binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ribosome binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables translation initiation factor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables translation initiation factor activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in HRI-mediated signaling IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in PERK-mediated unfolded protein response IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in PERK-mediated unfolded protein response NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in cellular response to UV ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to amino acid starvation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to heat IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to oxidative stress ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in mitophagy IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of translational initiation in response to stress ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of type B pancreatic cell apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of translation in response to endoplasmic reticulum stress IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of translational initiation in response to stress IEA
Inferred from Electronic Annotation
more info
  
involved_in response to endoplasmic reticulum stress IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to endoplasmic reticulum stress IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in response to endoplasmic reticulum stress ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in response to kainic acid IEA
Inferred from Electronic Annotation
more info
  
involved_in response to manganese-induced endoplasmic reticulum stress IEA
Inferred from Electronic Annotation
more info
  
involved_in stress granule assembly ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in translational initiation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in translational initiation IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in cytoplasmic stress granule ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
part_of eukaryotic 48S preinitiation complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of eukaryotic translation initiation factor 2 complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of eukaryotic translation initiation factor 2 complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of eukaryotic translation initiation factor 2 complex IPI
Inferred from Physical Interaction
more info
 PubMed 
located_in extracellular exosome HDA PubMed 
located_in glial limiting end-foot IEA
Inferred from Electronic Annotation
more info
  
located_in membrane HDA PubMed 
is_active_in mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  
located_in synapse IEA
Inferred from Electronic Annotation
more info
  
part_of translation initiation ternary complex IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
eukaryotic translation initiation factor 2 subunit 1
Names
eIF-2-alpha
eIF2-alpha
eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_004094.5 → NP_004085.1  eukaryotic translation initiation factor 2 subunit 1

    See identical proteins and their annotated locations for NP_004085.1

    Status: VALIDATED

    Source sequence(s)
    AL139785, BC002513
    Consensus CDS
    CCDS9781.1
    UniProtKB/Swiss-Prot
    P05198
    UniProtKB/TrEMBL
    G3V4T5, Q53XC0
    Related
    ENSP00000256383.4, ENST00000256383.11
    Conserved Domains (1) summary
    PTZ00248
    Location:4 → 315
    PTZ00248; eukaryotic translation initiation factor 2 subunit 1; Provisional

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

    Range
    67360328..67386516
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060938.1 Alternate T2T-CHM13v2.0

    Range
    61567453..61593639
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P05198.3 GenPept UniProtKB/Swiss-Prot:P05198

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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