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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
    mouse all
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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

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

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