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P05198

- IF2A_HUMAN

UniProt

P05198 - IF2A_HUMAN

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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

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. ribosome binding Source: UniProtKB
  3. 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
Complete GO annotation...

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
Complete GO annotation...

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

BgeeiP05198.
CleanExiHS_EIF2A.
HS_EIF2S1.
ExpressionAtlasiP05198. baseline and differential.
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.
EIF2S2P200425EBI-1056162,EBI-711977
EIF2S3P410914EBI-1056162,EBI-1054228

Protein-protein interaction databases

BioGridi108285. 51 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 – 136Combined sources
Beta strandi19 – 279Combined sources
Beta strandi29 – 368Combined sources
Turni37 – 415Combined sources
Beta strandi43 – 475Combined sources
Helixi48 – 503Combined sources
Turni60 – 623Combined sources
Beta strandi64 – 663Combined sources
Beta strandi68 – 7710Combined sources
Turni78 – 814Combined sources
Beta strandi82 – 876Combined sources
Helixi92 – 11827Combined sources
Helixi124 – 13310Combined sources
Helixi135 – 1428Combined sources
Helixi147 – 15812Combined sources
Helixi160 – 1634Combined sources
Helixi170 – 18213Combined sources
Beta strandi190 – 1934Combined sources
Turni202 – 2043Combined sources
Helixi205 – 21713Combined sources
Beta strandi218 – 2203Combined sources
Beta strandi225 – 2317Combined sources
Beta strandi234 – 2407Combined sources
Helixi244 – 26320Combined sources
Helixi282 – 2898Combined sources
Helixi293 – 2953Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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. S1_dom.
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

        10         20         30         40         50
MPGLSCRFYQ HKFPEVEDVV MVNVRSIAEM GAYVSLLEYN NIEGMILLSE
60 70 80 90 100
LSRRRIRSIN KLIRIGRNEC VVVIRVDKEK GYIDLSKRRV SPEEAIKCED
110 120 130 140 150
KFTKSKTVYS ILRHVAEVLE YTKDEQLESL FQRTAWVFDD KYKRPGYGAY
160 170 180 190 200
DAFKHAVSDP SILDSLDLNE DEREVLINNI NRRLTPQAVK IRADIEVACY
210 220 230 240 250
GYEGIDAVKE ALRAGLNCST ENMPIKINLI APPRYVMTTT TLERTEGLSV
260 270 280 290 300
LSQAMAVIKE KIEEKRGVFN VQMEPKVVTD TDETELARQM ERLERENAEV
310
DGDDDAEEME AKAED
Length:315
Mass (Da):36,112
Last modified:January 23, 2007 - v3
Checksum:iFF3E75E3816E6B1E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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. 51 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

Bgeei P05198.
CleanExi HS_EIF2A.
HS_EIF2S1.
ExpressionAtlasi P05198. baseline and differential.
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. S1_dom.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 158 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