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IID00508
UniprotP05198
ProteinEukaryotic translation initiation factor 2 subunit 1
GeneEIF2S1
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
xml
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
315
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 2-183 Monomer :
 Evidence X-RAY 1kl9 A Reference
       Region 1kl9 A 2-3 disorder
       Region 1kl9 A 4-51 order
       Region 1kl9 A 52-63 disorder
       Region 1kl9 A 64-183 order
Seq 5-303 Monomer :
 Evidence NMR 1q8k A Reference
       Region 1q8k A 5-303 order
Seqphosphorylation
    49-49 Phosphoserine; by HRI
    52-52 Phosphoserine
    158-158 Phosphoserine
    279-279 Phosphothreonine
    281-281 Phosphothreonine
Seqacetylation
    141-141 N6-acetyllysine
 
Prediction
NeProc
Disorder 1-1,282-282,311-315
Order 2-281,283-310
ProS 282-282
AlphaFold
Disorder 1-12,55-56,142-148,163-168,185-187,221-222,293-293,296-315
Order 13-54,57-141,149-162,169-184,188-220,223-292,294-295
Pfam Hmmer
PF00575 13-88 4.2e-16
PF07541 129-244 2.5e-66
SEG 46-59 ,296-315
Function
Function in SwissProt
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).