UniProt:P05198 EIF2S1

chain
  • chain:1-315
checksum FF3E75E3816E6B1E
comment
  • 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). 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/ 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).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).SUBUNIT Eukaryotic translation initiation factor 2 eIF2 is a heterotrimeric complex composed of an alpha (EIF2S1), a beta (EIF2S2) and a gamma (EIF2S3) chain (PubMed:23063529, PubMed:31836389, PubMed:35031321, PubMed:31048492). eIF2 is member of the 43S pre-initiation complex (43S PIC). eIF2 forms a complex with at least CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5 (By similarity). Interaction with METAP2 protects EIF2S1 from inhibitory phosphorylation (By similarity). Interacts with ABCF1 isoform 2 (PubMed:17894550). Associates with ribosomes (PubMed:17894550). Interacts with DDX3X in an RNA-independent manner (PubMed:18596238). Interacts with CDC123 (PubMed:31836389, PubMed:35031321).SUBUNIT (Microbial infection) Interacts with rotavirus A non-structural protein 2; this interaction probably plays a role in the sequestration of IF2A in viral factories (PubMed:30258011). Interacts with rotavirus A non-structural protein 5; this interaction probably plays a role in its sequestration in viral factories (PubMed:30258011).INTERACTION Colocalizes with NANOS3 in the stress granules.INDUCTION Up-regulated upon endoplasmic reticulum stress.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 eIF2 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, PubMed:31048492). 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).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 eIF2 between successive rounds of initiation and leading to global inhibition of translation.SIMILARITY Belongs to the eIF-2-alpha family.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.
crossReference
databaseName UniProt
dbId 72509
description
  • recommendedName: Eukaryotic translation initiation factor 2 subunit 1 alternativeName: Eukaryotic translation initiation factor 2 subunit alpha shortName: eIF-2-alpha shortName: eIF-2A shortName: eIF-2alpha shortName: eIF2-alpha
displayName UniProt:P05198 EIF2S1
geneName
  • EIF2S1
  • EIF2A
identifier P05198
isSequenceChanged false
keyword
  • 3D-structure
  • Acetylation
  • Cytoplasm
  • Initiation factor
  • Phosphoprotein
  • Protein biosynthesis
  • Reference proteome
  • RNA-binding
  • Translation regulation
modified [InstanceEdit:12187927] Wright, Adam, 2024-03-12
name
  • EIF2S1
otherIdentifier
  • 1154_at
  • 11716219_a_at
  • 11716220_x_at
  • 11716221_at
  • 11749910_a_at
  • 11752101_s_at
  • 16785631
  • 1965
  • 201142_PM_at
  • 201142_at
  • 201143_PM_s_at
  • 201143_s_at
  • 201144_PM_s_at
  • 201144_s_at
  • 3541139
  • 3541140
  • 3541141
  • 3541145
  • 3541146
  • 3541150
  • 3541152
  • 3541155
  • 3541157
  • 3541161
  • 3541163
  • 3541164
  • 3541165
  • 3541166
  • 3541167
  • 3541172
  • 39784_at
  • 7975224
  • A_14_P121759
  • A_14_P130960
  • A_24_P138556
  • A_24_P356015
  • A_33_P3402171
  • GE57464
  • GE891206
  • GO:0003676
  • GO:0003723
  • GO:0003743
  • GO:0005515
  • GO:0005576
  • GO:0005615
  • GO:0005634
  • GO:0005737
  • GO:0005829
  • GO:0005844
  • GO:0005850
  • GO:0006412
  • GO:0006413
  • GO:0006417
  • GO:0010494
  • GO:0012501
  • GO:0016020
  • GO:0023052
  • GO:0032057
  • GO:0033290
  • GO:0034063
  • GO:0034198
  • GO:0034599
  • GO:0034605
  • GO:0034644
  • GO:0034976
  • GO:0036490
  • GO:0036499
  • GO:0043022
  • GO:0043226
  • GO:0043558
  • GO:0044207
  • GO:0045182
  • GO:0045202
  • GO:0070062
  • GO:0097451
  • GO:1904373
  • GO:1990737
  • GO:2000676
  • HMNXSV003029192
  • Hs.151777.0.A3_3p_at
  • ILMN_1739821
  • J02645_at
  • PH_hs_0009146
  • TC14000406.hg
  • U26032_at
  • g12803384_3p_a_at
  • g4758255_3p_a_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • IF2A_HUMAN
sequenceLength 315
species [Species:48887] Homo sapiens
url https://purl.uniprot.org/uniprot/P05198
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