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P05198

- IF2A_HUMAN

UniProt

P05198 - IF2A_HUMAN

Protein

Eukaryotic translation initiation factor 2 subunit 1

Gene

EIF2S1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 156 (01 Oct 2014)
      Sequence version 3 (23 Jan 2007)
      Previous versions | rss
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    Functioni

    Functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S preinitiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B.

    GO - Molecular functioni

    1. poly(A) RNA binding Source: UniProtKB
    2. protein binding Source: UniProtKB
    3. ribosome binding Source: UniProtKB
    4. translation initiation factor activity Source: UniProtKB

    GO - Biological processi

    1. activation of signaling protein activity involved in unfolded protein response Source: Reactome
    2. cellular protein metabolic process Source: Reactome
    3. endoplasmic reticulum unfolded protein response Source: Reactome
    4. gene expression Source: Reactome
    5. protein autophosphorylation Source: Ensembl
    6. regulation of translational initiation in response to stress Source: Ensembl
    7. translation Source: Reactome
    8. translational initiation Source: Reactome

    Keywords - Molecular functioni

    Initiation factor

    Keywords - Biological processi

    Protein biosynthesis, Translation regulation

    Keywords - Ligandi

    RNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_1079. Formation of the ternary complex, and subsequently, the 43S complex.
    REACT_1815. Recycling of eIF2:GDP.
    REACT_18277. PERK regulates gene expression.
    REACT_1979. Translation initiation complex formation.
    REACT_2085. GTP hydrolysis and joining of the 60S ribosomal subunit.
    REACT_79. L13a-mediated translational silencing of Ceruloplasmin expression.
    REACT_931. Ribosomal scanning and start codon recognition.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Eukaryotic translation initiation factor 2 subunit 1
    Alternative name(s):
    Eukaryotic translation initiation factor 2 subunit alpha
    Short name:
    eIF-2-alpha
    Short name:
    eIF-2A
    Short name:
    eIF-2alpha
    Gene namesi
    Name:EIF2S1
    Synonyms:EIF2A
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:3265. EIF2S1.

    Subcellular locationi

    Cytoplasmic granule By similarity
    Note: The cytoplasmic granules are stress granules which are a dense aggregation in the cytosol composed of proteins and RNAs that appear when the cell is under stress. Colocalizes with NANOS3 in the stress granules By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasmic stress granule Source: UniProtKB
    2. cytosol Source: Reactome
    3. eukaryotic translation initiation factor 2 complex Source: InterPro
    4. extracellular vesicular exosome Source: UniProt
    5. membrane Source: UniProtKB
    6. nucleus Source: Ensembl
    7. polysome Source: ProtInc

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA27695.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 315315Eukaryotic translation initiation factor 2 subunit 1PRO_0000137382Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei49 – 491Phosphoserine; by HRIBy similarity
    Modified residuei52 – 521Phosphoserine1 Publication
    Modified residuei141 – 1411N6-acetyllysine1 Publication

    Post-translational modificationi

    Substrate for at least 4 kinases: EIF2AK3/PERK, GCN2, HRI and PKR. Phosphorylation stabilizes the eIF-2/GDP/eIF-2B complex and prevents GDP/GTP exchange reaction, thus impairing the recycling of eIF-2 between successive rounds of initiation and leading to global inhibition of translation. In case of infection by vaccinia virus or rotavirus A, eIF2S1 phosphorylation state is modulated.3 Publications

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiP05198.
    PaxDbiP05198.
    PeptideAtlasiP05198.
    PRIDEiP05198.

    2D gel databases

    OGPiP05198.
    REPRODUCTION-2DPAGEIPI00219678.

    PTM databases

    PhosphoSiteiP05198.

    Miscellaneous databases

    PMAP-CutDBP05198.

    Expressioni

    Gene expression databases

    ArrayExpressiP05198.
    BgeeiP05198.
    CleanExiHS_EIF2A.
    HS_EIF2S1.
    GenevestigatoriP05198.

    Organism-specific databases

    HPAiCAB011663.

    Interactioni

    Subunit structurei

    Heterotrimer composed of an alpha, a beta and a gamma chain. Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5. Interaction with METAP2 protects EIF2S1 from inhibitory phosphorylation By similarity. Interacts with ABCF1 isoform 2. Associates with ribosomes.By similarity1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    DDX3XO005713EBI-1056162,EBI-353779
    EIF2AK2P195254EBI-1056162,EBI-640775
    Eif2ak3Q9Z2B54EBI-1056162,EBI-1226344From a different organism.
    EIF2S2P200426EBI-1056162,EBI-711977
    EIF2S3P410914EBI-1056162,EBI-1054228

    Protein-protein interaction databases

    BioGridi108285. 49 interactions.
    DIPiDIP-39418N.
    IntActiP05198. 17 interactions.
    MINTiMINT-2983901.
    STRINGi9606.ENSP00000256383.

    Structurei

    Secondary structure

    1
    315
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi8 – 136
    Beta strandi19 – 279
    Beta strandi29 – 368
    Turni37 – 415
    Beta strandi43 – 475
    Helixi48 – 503
    Turni60 – 623
    Beta strandi64 – 663
    Beta strandi68 – 7710
    Turni78 – 814
    Beta strandi82 – 876
    Helixi92 – 11827
    Helixi124 – 13310
    Helixi135 – 1428
    Helixi147 – 15812
    Helixi160 – 1634
    Helixi170 – 18213
    Beta strandi190 – 1934
    Turni202 – 2043
    Helixi205 – 21713
    Beta strandi218 – 2203
    Beta strandi225 – 2317
    Beta strandi234 – 2407
    Helixi244 – 26320
    Helixi282 – 2898
    Helixi293 – 2953

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1KL9X-ray1.90A2-183[»]
    1Q8KNMR-A5-303[»]
    ProteinModelPortaliP05198.
    SMRiP05198. Positions 4-303.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP05198.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini17 – 8872S1 motifPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the eIF-2-alpha family.Curated
    Contains 1 S1 motif domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG1093.
    HOGENOMiHOG000199476.
    HOVERGENiHBG001910.
    InParanoidiP05198.
    KOiK03237.
    OMAiVMVQVRQ.
    OrthoDBiEOG7FZ012.
    PhylomeDBiP05198.
    TreeFamiTF101502.

    Family and domain databases

    Gene3Di1.10.150.190. 1 hit.
    2.40.50.140. 1 hit.
    3.30.70.1130. 1 hit.
    InterProiIPR012340. NA-bd_OB-fold.
    IPR003029. Rbsml_prot_S1_RNA-bd_dom.
    IPR022967. RNA-binding_domain_S1.
    IPR024055. TIF2_asu_C.
    IPR024054. TIF2_asu_middle.
    IPR011488. TIF_2_asu.
    [Graphical view]
    PfamiPF07541. EIF_2_alpha. 1 hit.
    PF00575. S1. 1 hit.
    [Graphical view]
    SMARTiSM00316. S1. 1 hit.
    [Graphical view]
    SUPFAMiSSF110993. SSF110993. 1 hit.
    SSF116742. SSF116742. 1 hit.
    SSF50249. SSF50249. 1 hit.
    PROSITEiPS50126. S1. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P05198-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPGLSCRFYQ HKFPEVEDVV MVNVRSIAEM GAYVSLLEYN NIEGMILLSE    50
    LSRRRIRSIN KLIRIGRNEC VVVIRVDKEK GYIDLSKRRV SPEEAIKCED 100
    KFTKSKTVYS ILRHVAEVLE YTKDEQLESL FQRTAWVFDD KYKRPGYGAY 150
    DAFKHAVSDP SILDSLDLNE DEREVLINNI NRRLTPQAVK IRADIEVACY 200
    GYEGIDAVKE ALRAGLNCST ENMPIKINLI APPRYVMTTT TLERTEGLSV 250
    LSQAMAVIKE KIEEKRGVFN VQMEPKVVTD TDETELARQM ERLERENAEV 300
    DGDDDAEEME AKAED 315
    Length:315
    Mass (Da):36,112
    Last modified:January 23, 2007 - v3
    Checksum:iFF3E75E3816E6B1E
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J02645 mRNA. Translation: AAA52373.1.
    BC002513 mRNA. Translation: AAH02513.1.
    CCDSiCCDS9781.1.
    RefSeqiNP_004085.1. NM_004094.4.
    UniGeneiHs.151777.

    Genome annotation databases

    EnsembliENST00000256383; ENSP00000256383; ENSG00000134001.
    ENST00000466499; ENSP00000425299; ENSG00000134001.
    GeneIDi1965.
    KEGGihsa:1965.
    UCSCiuc001xjg.3. human.

    Polymorphism databases

    DMDMi124200.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J02645 mRNA. Translation: AAA52373.1 .
    BC002513 mRNA. Translation: AAH02513.1 .
    CCDSi CCDS9781.1.
    RefSeqi NP_004085.1. NM_004094.4.
    UniGenei Hs.151777.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1KL9 X-ray 1.90 A 2-183 [» ]
    1Q8K NMR - A 5-303 [» ]
    ProteinModelPortali P05198.
    SMRi P05198. Positions 4-303.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108285. 49 interactions.
    DIPi DIP-39418N.
    IntActi P05198. 17 interactions.
    MINTi MINT-2983901.
    STRINGi 9606.ENSP00000256383.

    Chemistry

    ChEMBLi CHEMBL1255131.

    PTM databases

    PhosphoSitei P05198.

    Polymorphism databases

    DMDMi 124200.

    2D gel databases

    OGPi P05198.
    REPRODUCTION-2DPAGE IPI00219678.

    Proteomic databases

    MaxQBi P05198.
    PaxDbi P05198.
    PeptideAtlasi P05198.
    PRIDEi P05198.

    Protocols and materials databases

    DNASUi 1965.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000256383 ; ENSP00000256383 ; ENSG00000134001 .
    ENST00000466499 ; ENSP00000425299 ; ENSG00000134001 .
    GeneIDi 1965.
    KEGGi hsa:1965.
    UCSCi uc001xjg.3. human.

    Organism-specific databases

    CTDi 1965.
    GeneCardsi GC14P067826.
    HGNCi HGNC:3265. EIF2S1.
    HPAi CAB011663.
    MIMi 603907. gene.
    neXtProti NX_P05198.
    PharmGKBi PA27695.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1093.
    HOGENOMi HOG000199476.
    HOVERGENi HBG001910.
    InParanoidi P05198.
    KOi K03237.
    OMAi VMVQVRQ.
    OrthoDBi EOG7FZ012.
    PhylomeDBi P05198.
    TreeFami TF101502.

    Enzyme and pathway databases

    Reactomei REACT_1079. Formation of the ternary complex, and subsequently, the 43S complex.
    REACT_1815. Recycling of eIF2:GDP.
    REACT_18277. PERK regulates gene expression.
    REACT_1979. Translation initiation complex formation.
    REACT_2085. GTP hydrolysis and joining of the 60S ribosomal subunit.
    REACT_79. L13a-mediated translational silencing of Ceruloplasmin expression.
    REACT_931. Ribosomal scanning and start codon recognition.

    Miscellaneous databases

    ChiTaRSi EIF2S1. human.
    EvolutionaryTracei P05198.
    GeneWikii EIF2S1.
    GenomeRNAii 1965.
    NextBioi 7971.
    PMAP-CutDB P05198.
    PROi P05198.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P05198.
    Bgeei P05198.
    CleanExi HS_EIF2A.
    HS_EIF2S1.
    Genevestigatori P05198.

    Family and domain databases

    Gene3Di 1.10.150.190. 1 hit.
    2.40.50.140. 1 hit.
    3.30.70.1130. 1 hit.
    InterProi IPR012340. NA-bd_OB-fold.
    IPR003029. Rbsml_prot_S1_RNA-bd_dom.
    IPR022967. RNA-binding_domain_S1.
    IPR024055. TIF2_asu_C.
    IPR024054. TIF2_asu_middle.
    IPR011488. TIF_2_asu.
    [Graphical view ]
    Pfami PF07541. EIF_2_alpha. 1 hit.
    PF00575. S1. 1 hit.
    [Graphical view ]
    SMARTi SM00316. S1. 1 hit.
    [Graphical view ]
    SUPFAMi SSF110993. SSF110993. 1 hit.
    SSF116742. SSF116742. 1 hit.
    SSF50249. SSF50249. 1 hit.
    PROSITEi PS50126. S1. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and sequencing of complementary DNAs encoding the alpha-subunit of translational initiation factor eIF-2. Characterization of the protein and its messenger RNA."
      Ernst H., Duncan R.F., Hershey J.W.B.
      J. Biol. Chem. 262:1206-1212(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Fibroblast.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Placenta.
    3. "Inhibition of PKR by vaccinia virus: role of the N- and C-terminal domains of E3L."
      Langland J.O., Jacobs B.L.
      Virology 324:419-429(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION STATE REGULATION BY VACCINIA VIRUS PROTEIN E3.
    4. "The N-terminal region of ABC50 interacts with eukaryotic initiation factor eIF2 and is a target for regulatory phosphorylation by CK2."
      Paytubi S., Morrice N.A., Boudeau J., Proud C.G.
      Biochem. J. 409:223-231(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ABCF1, ASSOCIATION WITH RIBOSOMES.
    5. "Rotavirus infection induces the phosphorylation of eIF2alpha but prevents the formation of stress granules."
      Montero H., Rojas M., Arias C.F., Lopez S.
      J. Virol. 82:1496-1504(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION STATE REGULATION BY ROTAVIRUS A.
    6. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    7. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
      Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
      Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-141, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    9. "Crystal structure of the N-terminal segment of human eukaryotic translation initiation factor 2alpha."
      Nonato M.C., Widom J., Clardy J.
      J. Biol. Chem. 277:17057-17061(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-183.
    10. "Solution structure of human initiation factor eIF2alpha reveals homology to the elongation factor eEF1B."
      Ito T., Marintchev A., Wagner G.
      Structure 12:1693-1704(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 5-303.

    Entry informationi

    Entry nameiIF2A_HUMAN
    AccessioniPrimary (citable) accession number: P05198
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 13, 1987
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 156 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 14
      Human chromosome 14: entries, gene names and cross-references to MIM
    2. Translation initiation factors
      List of translation initiation factor entries
    3. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    4. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3