Eif2s1
entrez
54318
canonical
uniprot
P68101
canonical
ensembl
ENSRNOG00000009432
resolver
ensembl
ENSRNOG00055018677
resolver
ensembl
ENSRNOG00060027849
resolver
ensembl
ENSRNOG00065018108
resolver
ensp
ENSRNOP00000013375
resolver
ensp
ENSRNOP00055025719
resolver
ensp
ENSRNOP00060040257
resolver
ensp
ENSRNOP00065024112
resolver
enst
ENSRNOT00000013375
resolver
enst
ENSRNOT00055031811
resolver
enst
ENSRNOT00060048341
resolver
enst
ENSRNOT00065030333
resolver
genesymbol
Eif2s1
resolver
genesymbol_syn
Eif2a
resolver
uniprot
P05199
resolver
uniprot_entry
IF2A_RAT
resolver
uniprot_sec
P05199
resolver
activity_regulation
ACTIVITY REGULATION: Activity is regulated by phosphorylation at Ser-49 and Ser-52, which stabilizes the eIF2/GDP/eIF2B complex and prevents the eIF2B-mediated exchange of GDP for GTP, thereby preventing the formation of the 43S pre-initiation complex (43S 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. {ECO:0000250|UniProtKB:P05198}.
uniprot
proteins
amino_acid_sequence
MPGLSCRFYQHKFPEVEDVVMVNVRSIAEMGAYVSLLEYNNIEGMILLSELSRRRIRSINKLIRIGRNECVVVIRVDKEKGYIDLSKRRVSPEEAIKCEDKFTKSKTVYSILRHVAEVLEYTKDEQLESLFQRTAWVFDDKYKRPGYGAYDAFKHAVSDPSILDSLDLNEDEREVLINNINRRLTPQAVKIRADIEVACYGYEGIDAVKEALRAGLNCSTETMPIKINLIAPPRYVMTTTTLERTEGLSVLNQAMAVIKEKIEEKRGVFNVQMEPKVVTDTDETELARQLERLERENAEVDGDDDAEEMEAKAED
uniprot
proteins
function
FUNCTION: Member of the eIF2 complex that 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 eIF2 and release of an eIF2-GDP binary complex. In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF2B. EIF2S1/eIF2-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/eIF2-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 activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming. EIF2S1/eIF2-alpha also acts as an activator of mitophagy in response to mitochondrial damage: phosphorylation by EIF2AK1/HRI promotes relocalization to the mitochondrial surface, thereby triggering PRKN-independent mitophagy (By similarity). {ECO:0000250|UniProtKB:P05198}.
uniprot
proteins
mass_dalton
36108
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-49 and Ser-52 stabilizes the eIF-2/GDP/eIF2B 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 (By similarity). Phosphorylation on Ser-52 by the EIF2AK4/GCN2 protein kinase occurs in response to amino acid starvation and UV irradiation (By similarity). Phosphorylation at Ser-52 by the EIF2AK3/PERK protein kinase occurs in response to the unfolded protein response (By similarity). Phosphorylation at Ser-52 by EIF2AK1/HRI in response to mitochondrial damage promotes relocalization to the mitochondrial surface (By similarity). {ECO:0000250|UniProtKB:P05198, ECO:0000250|UniProtKB:Q6ZWX6}.
uniprot
proteins
protein_family
EIF-2-alpha family
uniprot
proteins
pubmed
1346232
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
2948954
uniprot
proteins
sequence_length
315
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, Stress granule {ECO:0000250|UniProtKB:Q6ZWX6}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:P56286}. Mitochondrion {ECO:0000250|UniProtKB:P05198}. Note=Colocalizes with NANOS3 in the stress granules (By similarity). Relocalizes to the surface of mitochondria in response to mitochondrial damage and phosphorylation by EIF2AK1/HRI (By similarity). {ECO:0000250|UniProtKB:P05198, ECO:0000250|UniProtKB:Q6ZWX6}.
uniprot
proteins