UniProtKB - P05198 (IF2A_HUMAN)
Eukaryotic translation initiation factor 2 subunit 1
EIF2S1
Functioni
Functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA (PubMed:16289705).
This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex (PubMed:16289705).
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 (PubMed:16289705).
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 (PubMed:16289705).
EIF2S1/eIF-2-alpha is a key component of the integrated stress response (ISR), required for adaptation to various stress: phosphorylation by metabolic-stress sensing protein kinases (EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2) in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to an attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming (PubMed:19131336, PubMed:33384352).
3 PublicationsCaution
Activity regulationi
GO - Molecular functioni
- ribosome binding Source: UniProtKB
- RNA binding Source: UniProtKB
- translation initiation factor activity Source: UniProtKB
GO - Biological processi
- aging Source: Ensembl
- cellular response to amino acid starvation Source: UniProtKB
- cellular response to heat Source: Ensembl
- cellular response to oxidative stress Source: ARUK-UCL
- cellular response to UV Source: UniProtKB
- negative regulation of guanyl-nucleotide exchange factor activity Source: Ensembl
- negative regulation of translational initiation in response to stress Source: UniProtKB
- PERK-mediated unfolded protein response Source: UniProtKB
- positive regulation of neuron death Source: ParkinsonsUK-UCL
- positive regulation of type B pancreatic cell apoptotic process Source: Ensembl
- protein autophosphorylation Source: Ensembl
- regulation of translational initiation in response to stress Source: Ensembl
- response to endoplasmic reticulum stress Source: UniProtKB
- response to manganese-induced endoplasmic reticulum stress Source: Ensembl
- stress granule assembly Source: ARUK-UCL
Keywordsi
Molecular function | Initiation factor, RNA-binding |
Biological process | Protein biosynthesis, Translation regulation |
Enzyme and pathway databases
BRENDAi | 3.6.5.3, 2681 |
PathwayCommonsi | P05198 |
Reactomei | R-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 R-HSA-9633012, Response of EIF2AK4 (GCN2) to amino acid deficiency R-HSA-9648895, Response of EIF2AK1 (HRI) to heme deficiency |
SignaLinki | P05198 |
SIGNORi | P05198 |
Names & Taxonomyi
Protein namesi | Recommended name: Eukaryotic translation initiation factor 2 subunit 1Alternative name(s): Eukaryotic translation initiation factor 2 subunit alpha Short name: eIF-2-alpha Short name: eIF-2A Short name: eIF-2alpha |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3265, EIF2S1 |
MIMi | 603907, gene |
neXtProti | NX_P05198 |
VEuPathDBi | HostDB:ENSG00000134001 |
Subcellular locationi
Other locations
- Stress granule By similarity
Note: Colocalizes with NANOS3 in the stress granules.By similarity
Cytosol
- cytosol Source: HPA
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Nucleus
- nucleus Source: Ensembl
Other locations
- cytoplasmic stress granule Source: UniProtKB
- eukaryotic 48S preinitiation complex Source: GO_Central
- eukaryotic translation initiation factor 2 complex Source: UniProtKB
- eukaryotic translation initiation factor 2B complex Source: UniProtKB
- glial limiting end-foot Source: Ensembl
- membrane Source: UniProtKB
- multi-eIF complex Source: GO_Central
- polysome Source: ProtInc
- synapse Source: Ensembl
- translation initiation ternary complex Source: Ensembl
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Organism-specific databases
DisGeNETi | 1965 |
OpenTargetsi | ENSG00000134001 |
PharmGKBi | PA27695 |
Miscellaneous databases
Pharosi | P05198, Tbio |
Chemistry databases
ChEMBLi | CHEMBL1255131 |
Genetic variation databases
BioMutai | EIF2S1 |
DMDMi | 124200 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000137382 | 1 – 315 | Eukaryotic translation initiation factor 2 subunit 1Add BLAST | 315 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 49 | Phosphoserine; by HRIBy similarity | 1 | |
Modified residuei | 52 | PhosphoserineCombined sources | 1 | |
Modified residuei | 141 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 158 | PhosphoserineCombined sources | 1 | |
Modified residuei | 279 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 281 | PhosphothreonineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | P05198 |
jPOSTi | P05198 |
MassIVEi | P05198 |
PaxDbi | P05198 |
PeptideAtlasi | P05198 |
PRIDEi | P05198 |
ProteomicsDBi | 51824 |
TopDownProteomicsi | P05198 |
2D gel databases
OGPi | P05198 |
REPRODUCTION-2DPAGEi | IPI00219678 |
PTM databases
GlyGeni | P05198, 5 sites, 1 O-linked glycan (4 sites) |
iPTMneti | P05198 |
MetOSitei | P05198 |
PhosphoSitePlusi | P05198 |
SwissPalmi | P05198 |
Expressioni
Inductioni
Gene expression databases
Bgeei | ENSG00000134001, Expressed in testis and 245 other tissues |
ExpressionAtlasi | P05198, baseline and differential |
Genevisiblei | P05198, HS |
Organism-specific databases
HPAi | ENSG00000134001, Low tissue specificity |
Interactioni
Subunit structurei
Heterotrimer composed of an alpha, a beta and a gamma chain (PubMed:23063529).
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 (PubMed:17894550). Associates with ribosomes (PubMed:17894550).
Interacts with DDX3X in an RNA-independent manner (PubMed:18596238).
By similarity3 PublicationsBinary interactionsi
P05198
Protein-protein interaction databases
BioGRIDi | 108285, 170 interactors |
CORUMi | P05198 |
DIPi | DIP-39418N |
IntActi | P05198, 57 interactors |
MINTi | P05198 |
STRINGi | 9606.ENSP00000256383 |
Miscellaneous databases
RNActi | P05198, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P05198 |
BMRBi | P05198 |
SMRi | P05198 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P05198 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 17 – 88 | S1 motifPROSITE-ProRule annotationAdd BLAST | 72 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 293 – 315 | DisorderedSequence analysisAdd BLAST | 23 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 300 – 315 | Acidic residuesSequence analysisAdd BLAST | 16 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG2916, Eukaryota |
GeneTreei | ENSGT00390000007015 |
InParanoidi | P05198 |
OMAi | DVNEHQR |
OrthoDBi | 1093186at2759 |
PhylomeDBi | P05198 |
TreeFami | TF101502 |
Family and domain databases
CDDi | cd04452, S1_IF2_alpha, 1 hit |
Gene3Di | 1.10.150.190, 1 hit 2.40.50.140, 1 hit 3.30.70.1130, 1 hit |
IDEALi | IID00508 |
InterProi | View protein in InterPro IPR012340, NA-bd_OB-fold IPR022967, S1_dom IPR003029, S1_domain IPR044126, S1_IF2_alpha IPR024055, TIF2_asu_C IPR024054, TIF2_asu_middle_sf IPR011488, TIF_2_asu |
PANTHERi | PTHR10602, PTHR10602, 1 hit |
Pfami | View protein in Pfam PF07541, EIF_2_alpha, 1 hit PF00575, S1, 1 hit |
SMARTi | View protein in SMART SM00316, S1, 1 hit |
SUPFAMi | SSF110993, SSF110993, 1 hit SSF116742, SSF116742, 1 hit SSF50249, SSF50249, 1 hit |
PROSITEi | View protein in PROSITE PS50126, S1, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketG3V4T5 | G3V4T5_HUMAN | Eukaryotic translation initiation f... | EIF2S1 | 273 | Annotation score: | ||
H0YJS4 | H0YJS4_HUMAN | Eukaryotic translation initiation f... | EIF2S1 | 252 | Annotation score: |
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 |
Genome annotation databases
Ensembli | ENST00000256383.11; ENSP00000256383.4; ENSG00000134001.15 ENST00000466499.6; ENSP00000425299.1; ENSG00000134001.15 |
GeneIDi | 1965 |
KEGGi | hsa:1965 |
MANE-Selecti | ENST00000256383.11; ENSP00000256383.4; NM_004094.5; NP_004085.1 |
Similar proteinsi
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 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1KL9 | X-ray | 1.90 | A | 2-183 | [»] | |
1Q8K | NMR | - | A | 5-303 | [»] | |
6K71 | electron microscopy | 4.30 | K | 1-315 | [»] | |
6K72 | electron microscopy | 4.60 | K/L | 1-315 | [»] | |
6O81 | electron microscopy | 3.21 | L/M | 1-315 | [»] | |
6O85 | electron microscopy | 3.03 | L | 2-315 | [»] | |
6O9Z | electron microscopy | 3.03 | L/M | 2-315 | [»] | |
6YBV | electron microscopy | 3.80 | r | 1-315 | [»] | |
6ZMW | electron microscopy | 3.70 | r | 1-315 | [»] | |
6ZP4 | electron microscopy | 2.90 | O | 1-315 | [»] | |
7A09 | electron microscopy | 3.50 | O | 1-315 | [»] | |
7D43 | electron microscopy | 4.30 | K/L | 1-315 | [»] | |
7D44 | electron microscopy | 4.00 | K/L | 1-315 | [»] | |
7D45 | electron microscopy | 3.80 | K | 1-315 | [»] | |
7F66 | electron microscopy | 2.76 | N | 1-315 | [»] | |
7F67 | electron microscopy | 3.59 | N/Q | 1-315 | [»] | |
7NZM | electron microscopy | 3.96 | E | 2-187 | [»] | |
AlphaFoldDBi | P05198 | |||||
BMRBi | P05198 | |||||
SMRi | P05198 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108285, 170 interactors |
CORUMi | P05198 |
DIPi | DIP-39418N |
IntActi | P05198, 57 interactors |
MINTi | P05198 |
STRINGi | 9606.ENSP00000256383 |
Chemistry databases
ChEMBLi | CHEMBL1255131 |
PTM databases
GlyGeni | P05198, 5 sites, 1 O-linked glycan (4 sites) |
iPTMneti | P05198 |
MetOSitei | P05198 |
PhosphoSitePlusi | P05198 |
SwissPalmi | P05198 |
Genetic variation databases
BioMutai | EIF2S1 |
DMDMi | 124200 |
2D gel databases
OGPi | P05198 |
REPRODUCTION-2DPAGEi | IPI00219678 |
Proteomic databases
EPDi | P05198 |
jPOSTi | P05198 |
MassIVEi | P05198 |
PaxDbi | P05198 |
PeptideAtlasi | P05198 |
PRIDEi | P05198 |
ProteomicsDBi | 51824 |
TopDownProteomicsi | P05198 |
Protocols and materials databases
Antibodypediai | 3181, 896 antibodies from 39 providers |
DNASUi | 1965 |
Genome annotation databases
Ensembli | ENST00000256383.11; ENSP00000256383.4; ENSG00000134001.15 ENST00000466499.6; ENSP00000425299.1; ENSG00000134001.15 |
GeneIDi | 1965 |
KEGGi | hsa:1965 |
MANE-Selecti | ENST00000256383.11; ENSP00000256383.4; NM_004094.5; NP_004085.1 |
Organism-specific databases
CTDi | 1965 |
DisGeNETi | 1965 |
GeneCardsi | EIF2S1 |
HGNCi | HGNC:3265, EIF2S1 |
HPAi | ENSG00000134001, Low tissue specificity |
MIMi | 603907, gene |
neXtProti | NX_P05198 |
OpenTargetsi | ENSG00000134001 |
PharmGKBi | PA27695 |
VEuPathDBi | HostDB:ENSG00000134001 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2916, Eukaryota |
GeneTreei | ENSGT00390000007015 |
InParanoidi | P05198 |
OMAi | DVNEHQR |
OrthoDBi | 1093186at2759 |
PhylomeDBi | P05198 |
TreeFami | TF101502 |
Enzyme and pathway databases
BRENDAi | 3.6.5.3, 2681 |
PathwayCommonsi | P05198 |
Reactomei | R-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 R-HSA-9633012, Response of EIF2AK4 (GCN2) to amino acid deficiency R-HSA-9648895, Response of EIF2AK1 (HRI) to heme deficiency |
SignaLinki | P05198 |
SIGNORi | P05198 |
Miscellaneous databases
BioGRID-ORCSi | 1965, 794 hits in 1055 CRISPR screens |
EvolutionaryTracei | P05198 |
GeneWikii | EIF2S1 |
GenomeRNAii | 1965 |
Pharosi | P05198, Tbio |
PROi | PR:P05198 |
RNActi | P05198, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000134001, Expressed in testis and 245 other tissues |
ExpressionAtlasi | P05198, baseline and differential |
Genevisiblei | P05198, HS |
Family and domain databases
CDDi | cd04452, S1_IF2_alpha, 1 hit |
Gene3Di | 1.10.150.190, 1 hit 2.40.50.140, 1 hit 3.30.70.1130, 1 hit |
IDEALi | IID00508 |
InterProi | View protein in InterPro IPR012340, NA-bd_OB-fold IPR022967, S1_dom IPR003029, S1_domain IPR044126, S1_IF2_alpha IPR024055, TIF2_asu_C IPR024054, TIF2_asu_middle_sf IPR011488, TIF_2_asu |
PANTHERi | PTHR10602, PTHR10602, 1 hit |
Pfami | View protein in Pfam PF07541, EIF_2_alpha, 1 hit PF00575, S1, 1 hit |
SMARTi | View protein in SMART SM00316, S1, 1 hit |
SUPFAMi | SSF110993, SSF110993, 1 hit SSF116742, SSF116742, 1 hit SSF50249, SSF50249, 1 hit |
PROSITEi | View protein in PROSITE PS50126, S1, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | IF2A_HUMAN | |
Accessioni | P05198Primary (citable) accession number: P05198 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 13, 1987 |
Last sequence update: | January 23, 2007 | |
Last modified: | May 25, 2022 | |
This is version 220 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Translation initiation factors
List of translation initiation factor entries - Human chromosome 14
Human chromosome 14: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families