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

Gene ID: 1965, updated on 17-Jun-2019

Summary

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
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

Genomic context

See EIF2S1 in Genome Data Viewer
Location:
14q23.3
Exon count:
8
Annotation release Status Assembly Chr Location
109.20190607 current GRCh38.p13 (GCF_000001405.39) 14 NC_000014.9 (67360328..67386516)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (67827034..67853233)

Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene gephyrin Neighboring gene membrane palmitoylated protein 5 Neighboring gene GATA motif-containing MPRA enhancer 49 Neighboring gene ATPase H+ transporting V1 subunit D Neighboring gene pleckstrin 2

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

HIV-1 interactions

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 BioSystems

  • ABC-family proteins mediated transport, organism-specific biosystem (from REACTOME)
    ABC-family proteins mediated transport, organism-specific biosystemThe ATP-binding cassette (ABC) superfamily of active transporters involves a large number of functionally diverse transmembrane proteins. They transport a variety of compounds through membranes agai...
  • Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S, organism-specific biosystem (from REACTOME)
    Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S, organism-specific biosystemThe cap-binding complex is constituted by the initiation factors eIF4A, eIF4G and eIF4E. First, eIF4E must be released from the inactive eIF4E:4E-BP complex. Then eIF4A interacts with eIF4G, and eIF...
  • Apoptosis, organism-specific biosystem (from KEGG)
    Apoptosis, organism-specific biosystemApoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled...
  • Apoptosis, conserved biosystem (from KEGG)
    Apoptosis, conserved biosystemApoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled...
  • Autophagy - animal, organism-specific biosystem (from KEGG)
    Autophagy - animal, organism-specific biosystemAutophagy (or macroautophagy) is a cellular catabolic pathway involving in protein degradation, organelle turnover, and non-selective breakdown of cytoplasmic components, which is evolutionarily cons...
  • Autophagy - animal, conserved biosystem (from KEGG)
    Autophagy - animal, conserved biosystemAutophagy (or macroautophagy) is a cellular catabolic pathway involving in protein degradation, organelle turnover, and non-selective breakdown of cytoplasmic components, which is evolutionarily cons...
  • Brain-Derived Neurotrophic Factor (BDNF) signaling pathway, organism-specific biosystem (from WikiPathways)
    Brain-Derived Neurotrophic Factor (BDNF) signaling pathway, organism-specific biosystemBrain-derived neurotrophic factor (BDNF) is a neurotrophin essential for growth, differentiation, plasticity, and survival of neurons. BDNF is also required for processes such as energy metabolism, b...
  • Cap-dependent Translation Initiation, organism-specific biosystem (from REACTOME)
    Cap-dependent Translation Initiation, organism-specific biosystemTranslation initiation is a complex process in which the Met-tRNAi initiator, 40S, and 60S ribosomal subunits are assembled by eukaryotic initiation factors (eIFs) into an 80S ribosome at the start c...
  • Eukaryotic Translation Initiation, organism-specific biosystem (from REACTOME)
    Eukaryotic Translation Initiation, organism-specific biosystemInitiation of translation in the majority of eukaryotic cellular mRNAs depends on the 5'-cap (m7GpppN) and involves ribosomal scanning of the 5' untranslated region (5'-UTR) for an initiating AUG sta...
  • Formation of the ternary complex, and subsequently, the 43S complex, organism-specific biosystem (from REACTOME)
    Formation of the ternary complex, and subsequently, the 43S complex, organism-specific biosystemBinding of the methionyl-tRNA initiator to the active eIF2:GTP complex results in the formation of the ternary complex. Subsequently, this Met-tRNAi:eIF2:GTP (ternary) complex binds to the complex fo...
  • GTP hydrolysis and joining of the 60S ribosomal subunit, organism-specific biosystem (from REACTOME)
    GTP hydrolysis and joining of the 60S ribosomal subunit, organism-specific biosystemHydrolysis of eIF2-GTP occurs after the Met-tRNAi has recognized the AUG. This reaction is catalyzed by eIF5 (or eIF5B) and is thought to cause dissociation of all other initiation factors and allow ...
  • Gene Expression, organism-specific biosystem (from REACTOME)
    Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
  • Hepatitis C, organism-specific biosystem (from KEGG)
    Hepatitis C, organism-specific biosystemHepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the...
  • Hepatitis C, conserved biosystem (from KEGG)
    Hepatitis C, conserved biosystemHepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the...
  • Herpes simplex infection, organism-specific biosystem (from KEGG)
    Herpes simplex infection, organism-specific biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
  • Herpes simplex infection, conserved biosystem (from KEGG)
    Herpes simplex infection, conserved biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
  • Influenza A, organism-specific biosystem (from KEGG)
    Influenza A, organism-specific biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
  • Influenza A, conserved biosystem (from KEGG)
    Influenza A, conserved biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
  • L13a-mediated translational silencing of Ceruloplasmin expression, organism-specific biosystem (from REACTOME)
    L13a-mediated translational silencing of Ceruloplasmin expression, organism-specific biosystemWhile circularization of mRNA during translation initiation is thought to contribute to an increase in the efficiency of translation, it also appears to provide a mechanism for translational silencin...
  • Measles, organism-specific biosystem (from KEGG)
    Measles, organism-specific biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
  • Measles, conserved biosystem (from KEGG)
    Measles, conserved biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
  • Metabolism of proteins, organism-specific biosystem (from REACTOME)
    Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
  • Non-alcoholic fatty liver disease (NAFLD), organism-specific biosystem (from KEGG)
    Non-alcoholic fatty liver disease (NAFLD), organism-specific biosystemNon-alcoholic fatty liver disease (NAFLD) represents a spectrum ranging from simple steatosis to more severe steatohepatitis with hepatic inflammation and fibrosis, known as nonalcoholic steatohepati...
  • Non-alcoholic fatty liver disease (NAFLD), conserved biosystem (from KEGG)
    Non-alcoholic fatty liver disease (NAFLD), conserved biosystemNon-alcoholic fatty liver disease (NAFLD) represents a spectrum ranging from simple steatosis to more severe steatohepatitis with hepatic inflammation and fibrosis, known as nonalcoholic steatohepati...
  • PERK regulates gene expression, organism-specific biosystem (from REACTOME)
    PERK regulates gene expression, organism-specific biosystemPERK (EIF2AK3) is a single-pass transmembrane protein located in the endoplasmic reticulum (ER) membrane such that the N-terminus of PERK is luminal and the C-terminus is cytosolic. PERK is maintaine...
  • Protein processing in endoplasmic reticulum, organism-specific biosystem (from KEGG)
    Protein processing in endoplasmic reticulum, organism-specific biosystemThe endoplasmic reticulum (ER) is a subcellular organelle where proteins are folded with the help of lumenal chaperones. Newly synthesized peptides enter the ER via the sec61 pore and are glycosylate...
  • Protein processing in endoplasmic reticulum, conserved biosystem (from KEGG)
    Protein processing in endoplasmic reticulum, conserved biosystemThe endoplasmic reticulum (ER) is a subcellular organelle where proteins are folded with the help of lumenal chaperones. Newly synthesized peptides enter the ER via the sec61 pore and are glycosylate...
  • RNA transport, organism-specific biosystem (from KEGG)
    RNA transport, organism-specific biosystemRNA transport from the nucleus to the cytoplasm is fundamental for gene expression. The different RNA species that are produced in the nucleus are exported through the nuclear pore complexes (NPCs) ...
  • RNA transport, conserved biosystem (from KEGG)
    RNA transport, conserved biosystemRNA transport from the nucleus to the cytoplasm is fundamental for gene expression. The different RNA species that are produced in the nucleus are exported through the nuclear pore complexes (NPCs) ...
  • Recycling of eIF2:GDP, organism-specific biosystem (from REACTOME)
    Recycling of eIF2:GDP, organism-specific biosystemThe active eIF2:GTP complex may be formed by direct binding of GTP to free eIF2 or by GDP-GTP exchange on the eIF2:GDP:eIF2B complex. The eIF2:GDP complex binds eIF2B forming an eIF2:GDP:eIF2B interm...
  • Ribosomal scanning and start codon recognition, organism-specific biosystem (from REACTOME)
    Ribosomal scanning and start codon recognition, organism-specific biosystemThe 80S ribosome bound to the mRNA moves along the mRNA molecule from its initial site to the initiation codon and forms a 48S complex, in which the initiation codon is base paired to the anticodon o...
  • Translation, organism-specific biosystem (from REACTOME)
    Translation, organism-specific biosystemProtein synthesis is accomplished through the process of translation of an mRNA sequence into a polypeptide chain. This process can be divided into three distinct stages: initiation, elongation and ...
  • Translation Factors, organism-specific biosystem (from WikiPathways)
    Translation Factors, organism-specific biosystemProtein synthesis is the ultimate step of gene expression and a key control point for regulation. In particular, it enables cells to rapidly manipulate protein production without new mRNA synthesis, ...
  • Translation initiation complex formation, organism-specific biosystem (from REACTOME)
    Translation initiation complex formation, organism-specific biosystemThe translation initiation complex forms when the 43S complex binds the mRNA that is associated with eIF4F, eIF4B and eIF4H. eIF4G in the eIF4F complex can directly contact eIF3 in the 43S complex. e...
  • Transmembrane transport of small molecules, organism-specific biosystem (from REACTOME)
    Transmembrane transport of small molecules, organism-specific biosystem
    Transmembrane transport of small molecules
  • Unfolded Protein Response (UPR), organism-specific biosystem (from REACTOME)
    Unfolded Protein Response (UPR), organism-specific biosystemThe Unfolded Protein Response (UPR) is a regulatory system that protects the Endoplasmic Reticulum (ER) from overload. The UPR is provoked by the accumulation of improperly folded protein in the ER d...
  • Validated targets of C-MYC transcriptional activation, organism-specific biosystem (from Pathway Interaction Database)
    Validated targets of C-MYC transcriptional activation, organism-specific biosystem
    Validated targets of C-MYC transcriptional activation

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

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

General protein information

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

NCBI Reference Sequences (RefSeq)

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_004094.5NP_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
    Q53XC0
    Related
    ENSP00000256383.4, ENST00000256383.9
    Conserved Domains (1) summary
    cl26880
    Location:4315
    EIF_2_alpha; Eukaryotic translation initiation factor 2 alpha subunit

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000014.9 Reference GRCh38.p13 Primary Assembly

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