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Protein

Eukaryotic translation initiation factor 2 subunit 1

Gene

EIF2S1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

  • poly(A) RNA binding Source: UniProtKB
  • ribosome binding Source: UniProtKB
  • translation initiation factor activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Initiation factor

Keywords - Biological processi

Protein biosynthesis, Translation regulation

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000134001-MONOMER.
ReactomeiR-HSA-156827. L13a-mediated translational silencing of Ceruloplasmin expression.
R-HSA-381042. PERK regulates gene expression.
R-HSA-382556. ABC-family proteins mediated transport.
R-HSA-72649. Translation initiation complex formation.
R-HSA-72695. Formation of the ternary complex, and subsequently, the 43S complex.
R-HSA-72702. Ribosomal scanning and start codon recognition.
R-HSA-72706. GTP hydrolysis and joining of the 60S ribosomal subunit.
R-HSA-72731. Recycling of eIF2:GDP.
SIGNORiP05198.

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
Proteomesi
  • UP000005640 Componenti: 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

  • cytoplasmic stress granule Source: UniProtKB
  • cytosol Source: Reactome
  • eukaryotic 48S preinitiation complex Source: GO_Central
  • eukaryotic translation initiation factor 2 complex Source: GO_Central
  • extracellular exosome Source: UniProtKB
  • glial limiting end-foot Source: Ensembl
  • membrane Source: UniProtKB
  • multi-eIF complex Source: GO_Central
  • nucleus Source: Ensembl
  • polysome Source: ProtInc
  • ribosome Source: GO_Central
  • translation initiation ternary complex Source: Ensembl
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi1965.
OpenTargetsiENSG00000134001.
PharmGKBiPA27695.

Chemistry databases

ChEMBLiCHEMBL1255131.

Polymorphism and mutation databases

BioMutaiEIF2S1.
DMDMi124200.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001373821 – 315Eukaryotic translation initiation factor 2 subunit 1Add BLAST315

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei49Phosphoserine; by HRIBy similarity1
Modified residuei52PhosphoserineCombined sources1
Modified residuei141N6-acetyllysineCombined sources1
Modified residuei158PhosphoserineCombined sources1
Modified residuei279PhosphothreonineCombined sources1
Modified residuei281PhosphothreonineCombined sources1

Post-translational modificationi

Substrate for at least 4 kinases: EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2. 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 (PubMed:15207627, PubMed:18032499). Phosphorylated; phosphorylation on Ser-52 by the EIF2AK4/GCN2 protein kinase occurs in response to amino acid starvation and UV irradiation (By similarity).By similarity2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP05198.
PaxDbiP05198.
PeptideAtlasiP05198.
PRIDEiP05198.
TopDownProteomicsiP05198.

2D gel databases

OGPiP05198.
REPRODUCTION-2DPAGEIPI00219678.

PTM databases

iPTMnetiP05198.
PhosphoSitePlusiP05198.
SwissPalmiP05198.

Miscellaneous databases

PMAP-CutDBP05198.

Expressioni

Gene expression databases

BgeeiENSG00000134001.
CleanExiHS_EIF2A.
HS_EIF2S1.
ExpressionAtlasiP05198. baseline and differential.
GenevisibleiP05198. HS.

Organism-specific databases

HPAiCAB011663.
HPA064885.

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
ACTN1P128144EBI-1056162,EBI-351710
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. 66 interactors.
DIPiDIP-39418N.
IntActiP05198. 26 interactors.
MINTiMINT-2983901.
STRINGi9606.ENSP00000256383.

Structurei

Secondary structure

1315
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi8 – 13Combined sources6
Beta strandi19 – 27Combined sources9
Beta strandi29 – 36Combined sources8
Turni37 – 41Combined sources5
Beta strandi43 – 47Combined sources5
Helixi48 – 50Combined sources3
Turni60 – 62Combined sources3
Beta strandi64 – 66Combined sources3
Beta strandi68 – 77Combined sources10
Turni78 – 81Combined sources4
Beta strandi82 – 87Combined sources6
Helixi92 – 118Combined sources27
Helixi124 – 133Combined sources10
Helixi135 – 142Combined sources8
Helixi147 – 158Combined sources12
Helixi160 – 163Combined sources4
Helixi170 – 182Combined sources13
Beta strandi190 – 193Combined sources4
Turni202 – 204Combined sources3
Helixi205 – 217Combined sources13
Beta strandi218 – 220Combined sources3
Beta strandi225 – 231Combined sources7
Beta strandi234 – 240Combined sources7
Helixi244 – 263Combined sources20
Helixi282 – 289Combined sources8
Helixi293 – 295Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KL9X-ray1.90A2-183[»]
1Q8KNMR-A5-303[»]
ProteinModelPortaliP05198.
SMRiP05198.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05198.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini17 – 88S1 motifPROSITE-ProRule annotationAdd BLAST72

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG2916. Eukaryota.
COG1093. LUCA.
GeneTreeiENSGT00390000007015.
HOGENOMiHOG000199476.
HOVERGENiHBG001910.
InParanoidiP05198.
KOiK03237.
OMAiGVFNIQM.
OrthoDBiEOG091G07NN.
PhylomeDBiP05198.
TreeFamiTF101502.

Family and domain databases

Gene3Di1.10.150.190. 1 hit.
3.30.70.1130. 1 hit.
InterProiIPR012340. NA-bd_OB-fold.
IPR022967. S1_dom.
IPR003029. S1_domain.
IPR024055. TIF2_asu_C.
IPR024054. TIF2_asu_middle.
IPR011488. TIF_2_asu.
[Graphical view]
PANTHERiPTHR10602. PTHR10602. 1 hit.
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.

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KL9X-ray1.90A2-183[»]
1Q8KNMR-A5-303[»]
ProteinModelPortaliP05198.
SMRiP05198.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108285. 66 interactors.
DIPiDIP-39418N.
IntActiP05198. 26 interactors.
MINTiMINT-2983901.
STRINGi9606.ENSP00000256383.

Chemistry databases

ChEMBLiCHEMBL1255131.

PTM databases

iPTMnetiP05198.
PhosphoSitePlusiP05198.
SwissPalmiP05198.

Polymorphism and mutation databases

BioMutaiEIF2S1.
DMDMi124200.

2D gel databases

OGPiP05198.
REPRODUCTION-2DPAGEIPI00219678.

Proteomic databases

EPDiP05198.
PaxDbiP05198.
PeptideAtlasiP05198.
PRIDEiP05198.
TopDownProteomicsiP05198.

Protocols and materials databases

DNASUi1965.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000256383; ENSP00000256383; ENSG00000134001.
ENST00000466499; ENSP00000425299; ENSG00000134001.
GeneIDi1965.
KEGGihsa:1965.

Organism-specific databases

CTDi1965.
DisGeNETi1965.
GeneCardsiEIF2S1.
HGNCiHGNC:3265. EIF2S1.
HPAiCAB011663.
HPA064885.
MIMi603907. gene.
neXtProtiNX_P05198.
OpenTargetsiENSG00000134001.
PharmGKBiPA27695.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2916. Eukaryota.
COG1093. LUCA.
GeneTreeiENSGT00390000007015.
HOGENOMiHOG000199476.
HOVERGENiHBG001910.
InParanoidiP05198.
KOiK03237.
OMAiGVFNIQM.
OrthoDBiEOG091G07NN.
PhylomeDBiP05198.
TreeFamiTF101502.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000134001-MONOMER.
ReactomeiR-HSA-156827. L13a-mediated translational silencing of Ceruloplasmin expression.
R-HSA-381042. PERK regulates gene expression.
R-HSA-382556. ABC-family proteins mediated transport.
R-HSA-72649. Translation initiation complex formation.
R-HSA-72695. Formation of the ternary complex, and subsequently, the 43S complex.
R-HSA-72702. Ribosomal scanning and start codon recognition.
R-HSA-72706. GTP hydrolysis and joining of the 60S ribosomal subunit.
R-HSA-72731. Recycling of eIF2:GDP.
SIGNORiP05198.

Miscellaneous databases

ChiTaRSiEIF2S1. human.
EvolutionaryTraceiP05198.
GeneWikiiEIF2S1.
GenomeRNAii1965.
PMAP-CutDBP05198.
PROiP05198.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134001.
CleanExiHS_EIF2A.
HS_EIF2S1.
ExpressionAtlasiP05198. baseline and differential.
GenevisibleiP05198. HS.

Family and domain databases

Gene3Di1.10.150.190. 1 hit.
3.30.70.1130. 1 hit.
InterProiIPR012340. NA-bd_OB-fold.
IPR022967. S1_dom.
IPR003029. S1_domain.
IPR024055. TIF2_asu_C.
IPR024054. TIF2_asu_middle.
IPR011488. TIF_2_asu.
[Graphical view]
PANTHERiPTHR10602. PTHR10602. 1 hit.
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]
ProtoNetiSearch...

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 30, 2016
This is version 179 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.