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P05198 (IF2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:EIF2S1
Synonyms:EIF2A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length315 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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. Ref.4

Subcellular location

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.

Post-translational modification

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.

Sequence similarities

Belongs to the eIF-2-alpha family.

Contains 1 S1 motif domain.

Ontologies

Keywords
   Biological processProtein biosynthesis
Translation regulation
   LigandRNA-binding
   Molecular functionInitiation factor
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of signaling protein activity involved in unfolded protein response

Traceable author statement. Source: Reactome

cellular protein metabolic process

Traceable author statement. Source: Reactome

endoplasmic reticulum unfolded protein response

Traceable author statement. Source: Reactome

gene expression

Traceable author statement. Source: Reactome

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of translational initiation in response to stress

Inferred from electronic annotation. Source: Ensembl

translation

Traceable author statement. Source: Reactome

translational initiation

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasmic stress granule

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

eukaryotic translation initiation factor 2 complex

Inferred from electronic annotation. Source: InterPro

extracellular vesicular exosome

Inferred from direct assay PubMed 20458337. Source: UniProt

nucleus

Inferred from electronic annotation. Source: Ensembl

polysome

Traceable author statement Ref.1. Source: ProtInc

   Molecular_functionpoly(A) RNA binding

Inferred from direct assay PubMed 22658674PubMed 22681889. Source: UniProtKB

ribosome binding

Inferred from direct assay Ref.4. Source: UniProtKB

translation initiation factor activity

Inferred from direct assay PubMed 16289705. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 315315Eukaryotic translation initiation factor 2 subunit 1
PRO_0000137382

Regions

Domain17 – 8872S1 motif

Amino acid modifications

Modified residue491Phosphoserine; by HRI By similarity
Modified residue521Phosphoserine Ref.6
Modified residue1411N6-acetyllysine Ref.7

Secondary structure

............................................... 315
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P05198 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: FF3E75E3816E6B1E

FASTA31536,112
        10         20         30         40         50         60 
MPGLSCRFYQ HKFPEVEDVV MVNVRSIAEM GAYVSLLEYN NIEGMILLSE LSRRRIRSIN 

        70         80         90        100        110        120 
KLIRIGRNEC VVVIRVDKEK GYIDLSKRRV SPEEAIKCED KFTKSKTVYS ILRHVAEVLE 

       130        140        150        160        170        180 
YTKDEQLESL FQRTAWVFDD KYKRPGYGAY DAFKHAVSDP SILDSLDLNE DEREVLINNI 

       190        200        210        220        230        240 
NRRLTPQAVK IRADIEVACY GYEGIDAVKE ALRAGLNCST ENMPIKINLI APPRYVMTTT 

       250        260        270        280        290        300 
TLERTEGLSV LSQAMAVIKE KIEEKRGVFN VQMEPKVVTD TDETELARQM ERLERENAEV 

       310 
DGDDDAEEME AKAED 

« Hide

References

« Hide 'large scale' references
[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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J02645 mRNA. Translation: AAA52373.1.
BC002513 mRNA. Translation: AAH02513.1.
RefSeqNP_004085.1. NM_004094.4.
UniGeneHs.151777.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1KL9X-ray1.90A2-183[»]
1Q8KNMR-A5-303[»]
ProteinModelPortalP05198.
SMRP05198. Positions 4-303.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108285. 46 interactions.
IntActP05198. 17 interactions.
MINTMINT-2983901.
STRING9606.ENSP00000256383.

Chemistry

ChEMBLCHEMBL1255131.

PTM databases

PhosphoSiteP05198.

Polymorphism databases

DMDM124200.

2D gel databases

OGPP05198.
REPRODUCTION-2DPAGEIPI00219678.

Proteomic databases

PaxDbP05198.
PeptideAtlasP05198.
PRIDEP05198.

Protocols and materials databases

DNASU1965.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000256383; ENSP00000256383; ENSG00000134001.
ENST00000466499; ENSP00000425299; ENSG00000134001.
GeneID1965.
KEGGhsa:1965.
UCSCuc001xjg.3. human.

Organism-specific databases

CTD1965.
GeneCardsGC14P067826.
HGNCHGNC:3265. EIF2S1.
HPACAB011663.
MIM603907. gene.
neXtProtNX_P05198.
PharmGKBPA27695.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1093.
HOGENOMHOG000199476.
HOVERGENHBG001910.
InParanoidP05198.
KOK03237.
OMAVMVQVRQ.
OrthoDBEOG7FZ012.
PhylomeDBP05198.
TreeFamTF101502.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.
REACT_1762. 3' -UTR-mediated translational regulation.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpressP05198.
BgeeP05198.
CleanExHS_EIF2A.
HS_EIF2S1.
GenevestigatorP05198.

Family and domain databases

Gene3D1.10.150.190. 1 hit.
2.40.50.140. 1 hit.
3.30.70.1130. 1 hit.
InterProIPR012340. 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]
PfamPF07541. EIF_2_alpha. 1 hit.
PF00575. S1. 1 hit.
[Graphical view]
SMARTSM00316. S1. 1 hit.
[Graphical view]
SUPFAMSSF110993. SSF110993. 1 hit.
SSF116742. SSF116742. 1 hit.
SSF50249. SSF50249. 1 hit.
PROSITEPS50126. S1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSEIF2S1. human.
EvolutionaryTraceP05198.
GeneWikiEIF2S1.
GenomeRNAi1965.
NextBio7971.
PMAP-CutDBP05198.
PROP05198.
SOURCESearch...

Entry information

Entry nameIF2A_HUMAN
AccessionPrimary (citable) accession number: P05198
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 151 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Translation initiation factors

List of translation initiation factor entries

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM