EIF2S1
entrez
1965
canonical
uniprot
P05198
canonical
ensembl
ENSG00000134001
resolver
ensp
ENSP00000256383
resolver
ensp
ENSP00000425299
resolver
ensp
ENSP00000528902
resolver
ensp
ENSP00000586199
resolver
ensp
ENSP00000586200
resolver
enst
ENST00000256383
resolver
enst
ENST00000466499
resolver
enst
ENST00000858843
resolver
enst
ENST00000916140
resolver
enst
ENST00000916141
resolver
genesymbol
EIF2S1
resolver
genesymbol_syn
EIF2A
resolver
hgnc
HGNC:3265
resolver
uniprot
Q53XC0
resolver
uniprot_entry
IF2A_HUMAN
resolver
uniprot_entry
Q53XC0_HUMAN
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) (PubMed:15207627, PubMed:18032499). 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 (PubMed:19131336). {ECO:0000269|PubMed:15207627, ECO:0000269|PubMed:18032499, ECO:0000269|PubMed:19131336}.
uniprot
proteins
amino_acid_sequence
MPGLSCRFYQHKFPEVEDVVMVNVRSIAEMGAYVSLLEYNNIEGMILLSELSRRRIRSINKLIRIGRNECVVVIRVDKEKGYIDLSKRRVSPEEAIKCEDKFTKSKTVYSILRHVAEVLEYTKDEQLESLFQRTAWVFDDKYKRPGYGAYDAFKHAVSDPSILDSLDLNEDEREVLINNINRRLTPQAVKIRADIEVACYGYEGIDAVKEALRAGLNCSTENMPIKINLIAPPRYVMTTTTLERTEGLSVLSQAMAVIKEKIEEKRGVFNVQMEPKVVTDTDETELARQMERLERENAEVDGDDDAEEMEAKAED
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 (PubMed:16289705, PubMed:38340717). This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex (43S PIC) (PubMed:16289705). 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 (PubMed:16289705). 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 (PubMed:16289705). 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 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, PubMed:38340717). 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 (PubMed:38340717). {ECO:0000269|PubMed:16289705, ECO:0000269|PubMed:19131336, ECO:0000269|PubMed:33384352, ECO:0000269|PubMed:38340717}.
uniprot
proteins
mass_dalton
36112
uniprot
proteins
mutagenesis
MUTAGEN 52; /note="S->A: Abolished phosphorylation by EIF2AK1/HRI in response to stress. Abolished relocalization to the mitochondrial surface in response to mitochondrial damage."; /evidence="ECO:0000269|PubMed:38340717"; MUTAGEN 52; /note="S->D: Mimics phosphorylation; promotes relocalization to the mitochondrial surface in response to mitochondrial damage."; /evidence="ECO:0000269|PubMed:38340717
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 (PubMed:10026192, PubMed:15207627, PubMed:18032499, PubMed:19131336, PubMed:31048492). Substrate for at least 4 kinases: EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2 (PubMed:15489334, PubMed:38340717). 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 (PubMed:10026192). Phosphorylation at Ser-52 by EIF2AK1/HRI in response to mitochondrial damage promotes relocalization to the mitochondrial surface (PubMed:38340717). {ECO:0000250|UniProtKB:Q6ZWX6, ECO:0000269|PubMed:10026192, ECO:0000269|PubMed:15207627, ECO:0000269|PubMed:18032499, ECO:0000269|PubMed:19131336, ECO:0000269|PubMed:31048492, ECO:0000269|PubMed:38340717}.; PTM: (Microbial infection) Phosphorylation by vaccinia virus protein E3 and rotavirus A 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. {ECO:0000269|PubMed:15207627, ECO:0000269|PubMed:18032499}.
uniprot
proteins
protein_family
EIF-2-alpha family
uniprot
proteins
pubmed
10026192
uniprot
proteins
pubmed
11859078
uniprot
proteins
pubmed
15207627
uniprot
proteins
pubmed
15341733
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16289705
uniprot
proteins
pubmed
17894550
uniprot
proteins
pubmed
18032499
uniprot
proteins
pubmed
18596238
uniprot
proteins
pubmed
19131336
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
23063529
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
2948954
uniprot
proteins
pubmed
30258011
uniprot
proteins
pubmed
31048492
uniprot
proteins
pubmed
31836389
uniprot
proteins
pubmed
33384352
uniprot
proteins
pubmed
35031321
uniprot
proteins
pubmed
38340717
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:0000269|PubMed:38340717}. 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 (PubMed:38340717). {ECO:0000250|UniProtKB:Q6ZWX6, ECO:0000269|PubMed:38340717}.
uniprot
proteins