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EIF2A eukaryotic translation initiation factor 2A [ Homo sapiens (human) ]

Gene ID: 83939, updated on 27-Nov-2024

Summary

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Official Symbol
EIF2Aprovided by HGNC
Official Full Name
eukaryotic translation initiation factor 2Aprovided by HGNC
Primary source
HGNC:HGNC:3254
See related
Ensembl:ENSG00000144895 MIM:609234; AllianceGenome:HGNC:3254
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CDA02; EIF-2A; MST089; MSTP004; MSTP089
Summary
This gene encodes a eukaryotic translation initiation factor that catalyzes the formation of puromycin-sensitive 80 S preinitiation complexes and the poly(U)-directed synthesis of polyphenylalanine at low concentrations of Mg2+. This gene should not be confused with eIF2-alpha (EIF2S1, Gene ID: 1965), the alpha subunit of the eIF2 translation initiation complex. Although both of these proteins function in binding initiator tRNA to the 40 S ribosomal subunit, the encoded protein does so in a codon-dependent manner, whereas eIF2 complex requires GTP. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]
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 thyroid (RPKM 30.8), ovary (RPKM 23.5) and 25 other tissues See more
Orthologs
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Genomic context

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See EIF2A in Genome Data Viewer
Location:
3q25.1
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (150546787..150586016)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (153298042..153337277)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (150264574..150303803)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14814 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20686 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14815 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:150127902-150128781 Neighboring gene TSC22 domain family member 2 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_65259 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:150187015-150187515 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:150232752-150232908 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:150237884-150238384 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:150238385-150238885 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:150252356-150252475 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr3:150263870-150265069 Neighboring gene uncharacterized LOC124900547 Neighboring gene stress associated endoplasmic reticulum protein 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20688 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20689 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20690 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20691 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:150321219-150321992 Neighboring gene selenoprotein T Neighboring gene SAP30 pseudogene 1 Neighboring gene Sharpr-MPRA regulatory region 4372 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20694 Neighboring gene glutamate rich 6 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20695 Neighboring gene ERICH6 antisense RNA 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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

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Related articles in PubMed

  1. Mechanism and regulation of eukaryotic protein synthesis. Merrick WC. Microbiol Rev, 1992 Jun. PMID 1620067, Free PMC Article
  2. The Integrated Stress Response and Phosphorylated Eukaryotic Initiation Factor 2α in Neurodegeneration. Bond S, et al. J Neuropathol Exp Neurol, 2020 Feb 1. PMID 31913484, Free PMC Article
  3. Increased levels of eIF2A inhibit translation by sequestering 40S ribosomal subunits. Grove DJ, et al. Nucleic Acids Res, 2023 Oct 13. PMID 37602404, Free PMC Article
  4. Genome-wide CRISPR screens identify noncanonical translation factor eIF2A as an enhancer of SARS-CoV-2 programmed -1 ribosomal frameshifting. Wei LH, et al. Cell Rep, 2023 Aug 29. PMID 37581984
  5. Translation Regulation by eIF2α Phosphorylation and mTORC1 Signaling Pathways in Non-Communicable Diseases (NCDs). Rios-Fuller TJ, et al. Int J Mol Sci, 2020 Jul 26. PMID 32722591, Free PMC Article

See all (126) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. To initiate or not to initiate: A critical assessment of eIF2A, eIF2D, and MCT-1.DENR to deliver initiator tRNA to ribosomes.
    Title: To initiate or not to initiate: A critical assessment of eIF2A, eIF2D, and MCT-1·DENR to deliver initiator tRNA to ribosomes.
  2. Increased levels of eIF2A inhibit translation by sequestering 40S ribosomal subunits.
    Title: Increased levels of eIF2A inhibit translation by sequestering 40S ribosomal subunits.
  3. Genome-wide CRISPR screens identify noncanonical translation factor eIF2A as an enhancer of SARS-CoV-2 programmed -1 ribosomal frameshifting.
    Title: Genome-wide CRISPR screens identify noncanonical translation factor eIF2A as an enhancer of SARS-CoV-2 programmed -1 ribosomal frameshifting.
  4. The enterovirus genome can be translated in an IRES-independent manner that requires the initiation factors eIF2A/eIF2D.
    Title: The enterovirus genome can be translated in an IRES-independent manner that requires the initiation factors eIF2A/eIF2D.
  5. PKR-Mediated Phosphorylation of eIF2a and CHK1 Is Associated with Doxorubicin-Mediated Apoptosis in HCC1143 Triple-Negative Breast Cancer Cells.
    Title: PKR-Mediated Phosphorylation of eIF2a and CHK1 Is Associated with Doxorubicin-Mediated Apoptosis in HCC1143 Triple-Negative Breast Cancer Cells.
  6. The alternative initiation factor eIF2A plays key role in RAN translation of myotonic dystrophy type 2 CCUG*CAGG repeats.
    Title: The alternative initiation factor eIF2A plays key role in RAN translation of myotonic dystrophy type 2 CCUG•CAGG repeats.
  7. Downregulation of PHLPP induced by endoplasmic reticulum stress promotes eIF2alpha phosphorylation and chemoresistance in colon cancer.
    Title: Downregulation of PHLPP induced by endoplasmic reticulum stress promotes eIF2α phosphorylation and chemoresistance in colon cancer.
  8. CCCP-induced mitochondrial dysfunction - characterization and analysis of integrated stress response to cellular signaling and homeostasis.
    Title: CCCP-induced mitochondrial dysfunction - characterization and analysis of integrated stress response to cellular signaling and homeostasis.
  9. MARK2 phosphorylates eIF2alpha in response to proteotoxic stress.
    Title: MARK2 phosphorylates eIF2α in response to proteotoxic stress.
  10. The eIF2alpha kinase HRI in innate immunity, proteostasis, and mitochondrial stress.
    Title: The eIF2α kinase HRI in innate immunity, proteostasis, and mitochondrial stress.
Submit: New GeneRIF Correction See all GeneRIFs (28)

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
Tat tat HIV-1 Tat increases phosphorylation of EIF2A in astrocytes 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 cadherin binding HDA PubMed 
enables mRNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
  
enables ribosome binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ribosome binding IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables tRNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables tRNA binding IMP
Inferred from Mutant Phenotype
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 
enables translation initiation factor activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
involved_in SREBP signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of signal transduction IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of translation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in response to amino acid starvation IEA
Inferred from Electronic Annotation
more info
  
involved_in ribosome assembly IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in translational initiation IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in blood microparticle HDA PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
part_of cytosolic small ribosomal subunit 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 
located_in extracellular space HDA PubMed 

General protein information

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Preferred Names
eukaryotic translation initiation factor 2A
Names
65 kDa eukaryotic translation initiation factor 2A
eukaryotic translation initiation factor 2A, 65kDa

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_001319043.2 → NP_001305972.1  eukaryotic translation initiation factor 2A isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    AC107426
    Consensus CDS
    CCDS82861.1
    UniProtKB/Swiss-Prot
    Q9BY44
    Related
    ENSP00000420537.1, ENST00000487799.5
    Conserved Domains (3) summary
    pfam05308
    Location:411 → 496
    Mito_fiss_reg; Mitochondrial fission regulator
    pfam08662
    Location:191 → 386
    eIF2A; Eukaryotic translation initiation factor eIF2A
    sd00039
    Location:252 → 286
    7WD40; WD40 repeat [structural motif]

  2. NM_001319044.2 → NP_001305973.1  eukaryotic translation initiation factor 2A isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks two alternate in-frame exons in the coding region, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
    Source sequence(s)
    AC107426
    Consensus CDS
    CCDS82859.1
    UniProtKB/Swiss-Prot
    Q9BY44
    Related
    ENSP00000385292.3, ENST00000406576.7
    Conserved Domains (3) summary
    pfam05308
    Location:375 → 460
    Mito_fiss_reg; Mitochondrial fission regulator
    pfam08662
    Location:155 → 350
    eIF2A; Eukaryotic translation initiation factor eIF2A
    sd00039
    Location:42 → 81
    7WD40; WD40 repeat [structural motif]

  3. NM_001319045.2 → NP_001305974.1  eukaryotic translation initiation factor 2A isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate in-frame splice site in an internal exon, compared to variant 1. The encoded isoform (4) is shorter than isoform 1.
    Source sequence(s)
    AC107426
    Consensus CDS
    CCDS82860.1
    UniProtKB/TrEMBL
    F8WAE5
    Related
    ENSP00000273435.5, ENST00000273435.9
    Conserved Domains (3) summary
    COG5354
    Location:10 → 566
    COG5354; Uncharacterized protein, contains Trp-Asp (WD) repeat [General function prediction only]
    sd00039
    Location:272 → 306
    7WD40; WD40 repeat [structural motif]
    pfam08662
    Location:211 → 406
    eIF2A; Eukaryotic translation initiation factor eIF2A

  4. NM_001319046.2 → NP_001305975.1  eukaryotic translation initiation factor 2A isoform 5

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) has multiple differences in the 5' UTR and 5' coding region and initiates translation at an alternate start site, compared to variant 1. The encoded isoform (5) is shorter and has a distinct N-terminus, compared to isoform 1.
    Source sequence(s)
    AC107426
    UniProtKB/TrEMBL
    H7C5R5
    Conserved Domains (2) summary
    sd00039
    Location:63 → 97
    7WD40; WD40 repeat [structural motif]
    pfam08662
    Location:6 → 197
    eIF2A; Eukaryotic translation initiation factor eIF2A

  5. NM_032025.5 → NP_114414.2  eukaryotic translation initiation factor 2A isoform 1

    See identical proteins and their annotated locations for NP_114414.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AC107426
    Consensus CDS
    CCDS46935.1
    UniProtKB/Swiss-Prot
    A8MPS6, B4DF96, B4DQ14, D3DNI9, Q5QTR2, Q7Z4E9, Q8NFM1, Q96EW9, Q96K81, Q9BY44
    Related
    ENSP00000417229.1, ENST00000460851.6
    Conserved Domains (3) summary
    pfam05308
    Location:436 → 521
    Mito_fiss_reg; Mitochondrial fission regulator
    pfam08662
    Location:216 → 411
    eIF2A; Eukaryotic translation initiation factor eIF2A
    sd00039
    Location:277 → 311
    7WD40; WD40 repeat [structural motif]

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_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    150546787..150586016
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011513224.3 → XP_011511526.1  eukaryotic translation initiation factor 2A isoform X1

    Conserved Domains (2) summary
    pfam08662
    Location:216 → 411
    eIF2A; Eukaryotic translation initiation factor eIF2A
    sd00039
    Location:277 → 311
    7WD40; WD40 repeat [structural motif]

  2. XM_047449054.1 → XP_047305010.1  eukaryotic translation initiation factor 2A isoform X2

  3. XM_047449055.1 → XP_047305011.1  eukaryotic translation initiation factor 2A isoform X3

    Related
    ENSP00000420611.1, ENST00000465535.1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    153298042..153337277
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054348067.1 → XP_054204042.1  eukaryotic translation initiation factor 2A isoform X1

  2. XM_054348068.1 → XP_054204043.1  eukaryotic translation initiation factor 2A isoform X2

  3. XM_054348069.1 → XP_054204044.1  eukaryotic translation initiation factor 2A isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9BY44.3 GenPept UniProtKB/Swiss-Prot:Q9BY44

Gene LinkOut

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Chemical Information
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