EIF2S1
The translation initiation factor EIF2 catalyzes the first regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA to 40S ribosomal subunits. Binding occurs as a ternary complex of methionyl-tRNA, EIF2, and GTP. EIF2 is composed of 3 nonidentical subunits, the 36-kD EIF2-alpha subunit (EIF2S1), the 38-kD EIF2-beta subunit (EIF2S2; MIM 603908), and the 52-kD EIF2-gamma subunit (EIF2S3; MIM 300161). The rate of formation of the ternary complex is modulated by the phosphorylation state of EIF2-alpha (Ernst et al., 1987 [PubMed 2948954]).[supplied by OMIM, Feb 2010]
Full Name
Eukaryotic Translation Initiation Factor 2 Subunit Alpha
Research Area
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).
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).
Biological Process
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
Response to endoplasmic reticulum stress Source: UniProtKB
Response to manganese-induced endoplasmic reticulum stress Source: Ensembl
Stress granule assembly Source: ARUK-UCL
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
Response to endoplasmic reticulum stress Source: UniProtKB
Response to manganese-induced endoplasmic reticulum stress Source: Ensembl
Stress granule assembly Source: ARUK-UCL
Cellular Location
Stress granule. Colocalizes with NANOS3 in the stress granules.
PTM
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 (PubMed:15207627, PubMed:18032499, PubMed:19131336). Substrate for at least 4 kinases: EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2 (By similarity). Phosphorylated; phosphorylation on Ser-52 by the EIF2AK4/GCN2 protein kinase occurs in response to amino acid starvation and UV irradiation (By similarity).
(Microbial infection) Phosphorylation by vaccinia virus protein E3 and rotavirus A 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.
(Microbial infection) Phosphorylation by vaccinia virus protein E3 and rotavirus A 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.
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Anti-EIF2S1 antibodies
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CompareTarget: EIF2S1
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: CBNH-134
Application*: WB
Target: EIF2S1
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human, Rat, Zebrafish
Clone: 1E2
Application*: IP, WB
Target: EIF2S1
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: 6
Application*: WB, IH, IF, F
Target: EIF2S1
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human, Rat, Zebrafish
Clone: 1C11
Application*: IP
Target: EIF2S1
Host: Mouse
Antibody Isotype: IgG1, κ
Specificity: Human, Mouse, Rat
Clone: CAP1030
Application*: WB, E, IF
Target: EIF2S1
Host: Mouse
Antibody Isotype: IgG2b, κ
Specificity: Human, Mouse, Rat
Clone: CAP679
Application*: E, IF, WB, IP, P
Target: EIF2S1
Host: Rat
Antibody Isotype: IgG2b
Specificity: Human
Clone: L57A5
Application*: WB
Target: EIF2S1
Host: Mouse
Antibody Isotype: IgG2b
Specificity: Human, Mouse
Clone: 11
Application*: WB, IF
Target: EIF2S1
Host: Rat
Antibody Isotype: IgG2b
Specificity: Human
Clone: 59
Application*: WB
Target: EIF2S1
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: 119A11
Application*: WB, IF, IP, P, F
Target: EIF2S1
Host: Mouse
Antibody Isotype: IgG1, κ
Specificity: Human, Mouse, Rat
Clone: CBFYE-0666
Application*: E, IF, P, WB, IP
Target: EIF2S1
Host: Mouse
Antibody Isotype: IgG2b, κ
Specificity: Human
Clone: CBFYE-0665
Application*: WB
Target: EIF2S1
Host: Mouse
Antibody Isotype: IgG2
Specificity: Human, Mouse, Rat
Clone: CBFYE-0663
Application*: WB
Target: EIF2S1
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human, Mouse, Rat
Clone: 2E4
Application*: WB, IF, IP, P, F
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For Research Use Only. Not For Clinical Use.
(P): Predicted
* Abbreviations
- AActivation
- AGAgonist
- APApoptosis
- BBlocking
- BABioassay
- BIBioimaging
- CImmunohistochemistry-Frozen Sections
- CIChromatin Immunoprecipitation
- CTCytotoxicity
- CSCostimulation
- DDepletion
- DBDot Blot
- EELISA
- ECELISA(Cap)
- EDELISA(Det)
- ESELISpot
- EMElectron Microscopy
- FFlow Cytometry
- FNFunction Assay
- GSGel Supershift
- IInhibition
- IAEnzyme Immunoassay
- ICImmunocytochemistry
- IDImmunodiffusion
- IEImmunoelectrophoresis
- IFImmunofluorescence
- IHImmunohistochemistry
- IMImmunomicroscopy
- IOImmunoassay
- IPImmunoprecipitation
- ISIntracellular Staining for Flow Cytometry
- LALuminex Assay
- LFLateral Flow Immunoassay
- MMicroarray
- MCMass Cytometry/CyTOF
- MDMeDIP
- MSElectrophoretic Mobility Shift Assay
- NNeutralization
- PImmunohistologyp-Paraffin Sections
- PAPeptide Array
- PEPeptide ELISA
- PLProximity Ligation Assay
- RRadioimmunoassay
- SStimulation
- SESandwich ELISA
- SHIn situ hybridization
- TCTissue Culture
- WBWestern Blot
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