UniProtKB - P68101 (IF2A_RAT)
Protein
Eukaryotic translation initiation factor 2 subunit 1
Gene
Eif2s1
Organism
Rattus norvegicus (Rat)
Status
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 pre-initiation 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. 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 a attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming.By similarity
Caution
This gene should not be confused with EIF2A, with which it shares the alias EIF2A. Although both of these proteins function in binding initiator tRNA to the 40S ribosomal subunit, the eIF2 complex requires GTP, whereas the EIF2A protein does so in a codon-dependent manner.Curated
Activity regulationi
Activity is regulated by phosphorylation at Ser-49 and Ser-52, which stabilizes the eIF-2/GDP/eIF-2B complex and prevents the eIF-2B-mediated exchange of GDP for GTP, thereby preventing the formation of the 43S pre-initiation complex (PIC). This results in the global attenuation of 5' cap-dependent protein synthesis and concomitant translation of ISR-specific mRNAs that contain a short upstream open reading frame (uORF) in their 5' UTR, such as ATF4, ATF5, DDIT3/CHOP and PPP1R15A/GADD34.By similarity
GO - Molecular functioni
- ribosome binding Source: RGD
- RNA binding Source: GO_Central
- translation initiation factor activity Source: UniProtKB
GO - Biological processi
- aging Source: RGD
- cellular response to amino acid starvation Source: UniProtKB
- cellular response to heat Source: RGD
- cellular response to oxidative stress Source: RGD
- cellular response to UV Source: UniProtKB
- negative regulation of guanyl-nucleotide exchange factor activity Source: RGD
- negative regulation of translational initiation in response to stress Source: UniProtKB
- positive regulation of neuron death Source: RGD
- positive regulation of type B pancreatic cell apoptotic process Source: RGD
- protein autophosphorylation Source: RGD
- regulation of translational initiation in response to stress Source: RGD
- response to endoplasmic reticulum stress Source: UniProtKB
- response to manganese-induced endoplasmic reticulum stress Source: ParkinsonsUK-UCL
- stress granule assembly Source: RGD
- translation Source: RGD
Keywordsi
Molecular function | Initiation factor, RNA-binding |
Biological process | Protein biosynthesis, Translation regulation |
Enzyme and pathway databases
Reactomei | R-RNO-156827, L13a-mediated translational silencing of Ceruloplasmin expression R-RNO-381042, PERK regulates gene expression R-RNO-382556, ABC-family proteins mediated transport R-RNO-72649, Translation initiation complex formation R-RNO-72695, Formation of the ternary complex, and subsequently, the 43S complex R-RNO-72702, Ribosomal scanning and start codon recognition R-RNO-72706, GTP hydrolysis and joining of the 60S ribosomal subunit R-RNO-72731, Recycling of eIF2:GDP |
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 | Name:Eif2s1 Synonyms:Eif2a |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 620963, Eif2s1 |
Subcellular locationi
Other locations
- Stress granule By similarity
Note: Colocalizes with NANOS3 in the stress granules.By similarity
Cytosol
- cytosol Source: Ensembl
Nucleus
- nucleus Source: RGD
Other locations
- cytoplasm Source: RGD
- cytoplasmic stress granule Source: UniProtKB
- eukaryotic 48S preinitiation complex Source: GO_Central
- eukaryotic translation initiation factor 2 complex Source: RGD
- eukaryotic translation initiation factor 2B complex Source: UniProtKB
- glial limiting end-foot Source: RGD
- multi-eIF complex Source: GO_Central
- synapse Source: RGD
- translation initiation ternary complex Source: RGD
Keywords - Cellular componenti
CytoplasmPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000137386 | 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 | PhosphoserineBy similarity | 1 | |
Modified residuei | 141 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 158 | PhosphoserineBy similarity | 1 | |
Modified residuei | 279 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 281 | PhosphothreonineBy similarity | 1 |
Post-translational modificationi
Phosphorylation at Ser-49 and Ser-52 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, while concomitantly initiating the preferential translation of integrated stress response (ISR)-specific mRNAs (By similarity). Substrate for at least 4 kinases: EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2. Phosphorylated; phosphorylation on Ser-52 by the EIF2AK4/GCN2 protein kinase occurs in response to amino acid starvation and UV irradiation (By similarity).By similarity
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
jPOSTi | P68101 |
PaxDbi | P68101 |
PRIDEi | P68101 |
PTM databases
iPTMneti | P68101 |
PhosphoSitePlusi | P68101 |
Expressioni
Gene expression databases
Bgeei | ENSRNOG00000009432, Expressed in testis and 21 other tissues |
Genevisiblei | P68101, RN |
Interactioni
Subunit structurei
Heterotrimer composed of an alpha, a beta and a gamma chain (By similarity).
Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5 (By similarity). Interaction with METAP2 protects EIF2S1 from inhibitory phosphorylation (PubMed:1346232).
Interacts with ABCF1 (By similarity). Associates with ribosomes (By similarity).
Interacts with DDX3X in an RNA-independent manner (By similarity).
By similarity1 PublicationProtein-protein interaction databases
BioGRIDi | 248534, 2 interactors |
IntActi | P68101, 7 interactors |
STRINGi | 10116.ENSRNOP00000013375 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 17 – 88 | S1 motifPROSITE-ProRule annotationAdd BLAST | 72 |
Sequence similaritiesi
Belongs to the eIF-2-alpha family.Curated
Phylogenomic databases
eggNOGi | KOG2916, Eukaryota |
GeneTreei | ENSGT00390000007015 |
HOGENOMi | CLU_033458_0_0_1 |
InParanoidi | P68101 |
OMAi | DVNEHQR |
OrthoDBi | 1093186at2759 |
PhylomeDBi | P68101 |
TreeFami | TF101502 |
Family and domain databases
CDDi | cd04452, S1_IF2_alpha, 1 hit |
Gene3Di | 1.10.150.190, 1 hit 3.30.70.1130, 1 hit |
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 |
i Sequence
Sequence statusi: Complete.
P68101-1 [UniParc]FASTAAdd to basket
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 ETMPIKINLI APPRYVMTTT TLERTEGLSV
260 270 280 290 300
LNQAMAVIKE KIEEKRGVFN VQMEPKVVTD TDETELARQL ERLERENAEV
310
DGDDDAEEME AKAED
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J02646 mRNA Translation: AAA41110.1 BC087019 mRNA Translation: AAH87019.1 |
PIRi | A26711 |
RefSeqi | NP_062229.1, NM_019356.1 |
Genome annotation databases
Ensembli | ENSRNOT00000013375; ENSRNOP00000013375; ENSRNOG00000009432 |
GeneIDi | 54318 |
KEGGi | rno:54318 |
UCSCi | RGD:620963, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J02646 mRNA Translation: AAA41110.1 BC087019 mRNA Translation: AAH87019.1 |
PIRi | A26711 |
RefSeqi | NP_062229.1, NM_019356.1 |
3D structure databases
BMRBi | P68101 |
SMRi | P68101 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 248534, 2 interactors |
IntActi | P68101, 7 interactors |
STRINGi | 10116.ENSRNOP00000013375 |
PTM databases
iPTMneti | P68101 |
PhosphoSitePlusi | P68101 |
Proteomic databases
jPOSTi | P68101 |
PaxDbi | P68101 |
PRIDEi | P68101 |
Genome annotation databases
Ensembli | ENSRNOT00000013375; ENSRNOP00000013375; ENSRNOG00000009432 |
GeneIDi | 54318 |
KEGGi | rno:54318 |
UCSCi | RGD:620963, rat |
Organism-specific databases
CTDi | 1965 |
RGDi | 620963, Eif2s1 |
Phylogenomic databases
eggNOGi | KOG2916, Eukaryota |
GeneTreei | ENSGT00390000007015 |
HOGENOMi | CLU_033458_0_0_1 |
InParanoidi | P68101 |
OMAi | DVNEHQR |
OrthoDBi | 1093186at2759 |
PhylomeDBi | P68101 |
TreeFami | TF101502 |
Enzyme and pathway databases
Reactomei | R-RNO-156827, L13a-mediated translational silencing of Ceruloplasmin expression R-RNO-381042, PERK regulates gene expression R-RNO-382556, ABC-family proteins mediated transport R-RNO-72649, Translation initiation complex formation R-RNO-72695, Formation of the ternary complex, and subsequently, the 43S complex R-RNO-72702, Ribosomal scanning and start codon recognition R-RNO-72706, GTP hydrolysis and joining of the 60S ribosomal subunit R-RNO-72731, Recycling of eIF2:GDP |
Miscellaneous databases
PROi | PR:P68101 |
Gene expression databases
Bgeei | ENSRNOG00000009432, Expressed in testis and 21 other tissues |
Genevisiblei | P68101, RN |
Family and domain databases
CDDi | cd04452, S1_IF2_alpha, 1 hit |
Gene3Di | 1.10.150.190, 1 hit 3.30.70.1130, 1 hit |
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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | IF2A_RAT | |
Accessioni | P68101Primary (citable) accession number: P68101 Secondary accession number(s): P05199 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 13, 1987 |
Last sequence update: | January 23, 2007 | |
Last modified: | February 10, 2021 | |
This is version 126 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - Translation initiation factors
List of translation initiation factor entries